bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters
Authors: Pasquali M. , Baiardini I. , Rogkakou A. , Riccio A.M. , Gamalero C. , Descalzi D. , Folli C. , Passalacqua G. , Canonica G.W. 
Published: September 2006

SummaryBackground
Levocetirizine (LCZ) has been shown to be effective in allergic rhinitis. We evaluated its clinical efficacy, antinflammatory actions and its effects on quality of life (QoL) with a specific instrument in the asthma–rhinitis comorbidity.Methods
Fifty adult patients with persistent rhinitis with/without asthma were enrolled. After a 1‐week run‐in for baseline evaluation, they were randomized to LCZ or placebo for 8 weeks. Cromolyn and salbutamol were permitted on demand. Rhinoconjunctivitis and asthma symptoms were evaluated by diary cards. QoL was assessed by the specific Rhinasthma questionnaire and the generic SF‐36 at different time‐points. Nasal scrapings and lavages were also performed for inflammatory cell count and mediator assessment.Results
Ten patients dropped out for unrelated reasons and the remaining completed the study with no side‐effect. Symptoms began to decrease in the active group at the second week of treatment when the difference with the placebo group became significant (0.05) and so remained until the end of the trial. Starting from 2 weeks of therapy, there was a significant decrease vs. baseline in all the four components of the Rhinasthma questionnaire only in the active group. The intergroup comparison became significant (P<0.05) at 4 weeks. The SF‐36 detected only sporadic differences between groups. Eosinophils and neutrophils in nasal scraping were significantly decreased in the LCZ group vs. baseline at all times. Nasal mediators were under the detection limits and no analysis could be performed. In the active group, only two patients used rescue medications compared with 13 patients in the placebo group.Conclusions
LCZ is clinically effective and capable of improving the rhinitis–asthma‐related QoL.
Airway hyper‐responsiveness in allergic asthma in guinea‐pigs is mediated by nerve growth factor via the induction of substance P: a potential role for trkA
Authors: De Vries A. , Engels F. , Henricks P. A. J. , Leusink‐Muis T. , McGregor G. P. , Braun A. , Groneberg D. A. , Dessing M. C. , Nijkamp F. P. , Fischer A. 
Published: September 2006

SummaryBackground: The neurotrophin nerve growth factor (NGF) has been implicated as a mediator in allergic asthma. Direct evidence that inhibition of NGF‐induced activation of neurotrophin receptors leads to improvement of airway symptoms is lacking. We therefore studied the effects of inhibitors of NGF signal transduction on the development of airway hyper‐responsiveness (AHR) and pulmonary inflammation in a guinea‐pig model for allergic asthma.Methods: Airway responsiveness to the contractile agonist histamine was measured in vivo in guinea‐pigs that were sensitized and challenged with ovalbumin (OVA). Inflammatory cell influx and NGF levels were determined in bronchoalveolar lavage fluid (BALF). Substance P, a key mediator of inflammation, was measured in lung tissue by radioimmunoassay, while substance P immunoreactive neurons in nodose ganglia were measured by immunohistochemistry.Results: OVA challenge induced an AHR after 24 h in OVA‐sensitized guinea‐pigs. This coincided with an increase in the amount of NGF in BALF. Simultaneously, an increase in the percentage of substance P immunoreactive neurons in the nodose ganglia and an increase in the amount of substance P in lung tissue were found. We used tyrosine kinase inhibitors to block the signal transduction of the high‐affinity NGF receptor, tyrosine kinase A (trkA). Treatment with the tyrosine kinase inhibitors (K252a or tyrphostin AG879) both inhibited the development of AHR, and prevented the increase in substance P in the nodose ganglia and lung tissue completely whereas both inhibitors had no effect on baseline airway resistance. Neither treatment with K252a or tyrphostin AG879 changed the influx of inflammatory cells in the BALF due to allergen challenge.Conclusions: We conclude that substance P plays a role in the induction of AHR in our model for allergic asthma which is most likely mediated by NGF. As both tyrosine kinase inhibitors AG879 and K252a show a similar inhibitory effect on airway function after allergen challenge, although both tyrosine kinase inhibitors exhibit different non‐specific inhibitory effects on targets other than trkA tyrosine kinases, it is likely that the induction of substance P derived from sensory nerves is mediated by NGF via its high‐affinity receptor trkA.
Association of interferon‐γ and interferon regulatory factor 1 polymorphisms with asthma in a family‐based association study in Taiwan
Authors: Wang T.‐N. , Chu Y.‐T. , Chen W.‐Y. , Feng W.‐W. , Shih N.‐H. , Hsiang C.‐H. , Ko Y.‐C. 
Published: September 2006

SummaryBackground
Asthma is a multi‐factorial disorder caused by complex interactions between genetic and environmental factors. IFN‐γ and IFN regulatory factor 1 (IRF‐1) affect Th1/Th2 cytokine balance, and influence the differentiation of Th2 cells, which influence the development of asthma.Objective
This study investigated CA repeats polymorphism of the IFN‐γ gene and GT repeats polymorphism of the IRF‐1 gene, which may predispose individuals to asthma pathogenesis.Methods
In the present study, we used the transmission/disequilibrium test (TDT) to investigate the relationship between asthma and the IFN‐γ and IRF‐1 polymorphisms by studying 348 subjects composed of 232 parents and 116 asthmatic children.Results
For global TDT test, IFN‐γ CA repeats and IRF‐1 GT repeat polymorphisms showed a significant association with asthma in children (P=0.009 and 0.017, respectively). We demonstrated that 13 CA repeats (138 bp) of IFN‐γ gene and 11 GT repeats (306 bp) of IRF‐1 gene are significantly preferentially transmitted to asthmatic children (T/NT=89/61, χ2=8.43, P<0.005 and T/NT=75/49, χ2=8.18, P<0.005, respectively). The offspring will have an increased risk of asthma when their parents transmit IFN‐γ 13 CA repeats (OR=1.83, P=0.009) and IRF1 11 GT repeats (OR=1.88, P=0.007) to them. But we observed that the IFN‐γ and IRF‐1 polymorphisms are not associated with IgE concentrations.Conclusion
These findings provide strong evidence of which IFN‐γ CA repeat and IRF‐1 GT repeat polymorphisms influence the risk of asthma for children in Taiwan.
Identification of key peptide-specific CD4+ T cell responses to human cytomegalovirus: implications for tracking antiviral populations
Authors: Harcourt G C , Scriba T J , Semmo N , Bounds S , Taylor E , Klenerman P 
Published: September 2006

SummaryHuman cytomegalovirus (CMV) infection is normally controlled effectively by the immune response, including CD4+ T cells. Large numbers of these cells are present in healthy seropositive individuals but their loss in immunosuppression leads to reactivation and disease. Tracking such responses in vivo is hampered by poor definition of their peptide targets. In this study, we defined the key targets of the peptide-specific CD4+ T cell responses to the CMV pp65 protein using functional assays and a peptide library. Despite a good deal of interindividual variation in the numbers of peptides recognized, responses to CMV pp65 were strikingly targeted at three key epitopes. A response to one or more of these three key peptides was seen in all individuals tested (P &lt; 0·0001) and this finding was tested and reproduced in a second independent population. The most common response identified was that to a DR53 restricted epitope, aa281–295. HLA-DR1 restricted CMV pp65-specific populations, although reproducibly detected, were of low frequency ex vivo. However, it was possible to detect and phenotype these cells using an enrichment protocol and this revealed them to have ‘effector memory’ status although, in contrast to CD8+ T cell responses, these were CD45RA–. These data suggest that CD4+ T cell responses to CMV can be identified reliably using a pool of just three peptides. This simple approach will provide a robust and reliable as well as economic method for tracking peptide specific populations in health and disease.
The sodium‐iodide symporter expression in placental tissue at different gestational age: an immunohistochemical study
Authors: Di Cosmo C. , Fanelli G. , Tonacchera M. , Ferrarini E. , Dimida A. , Agretti P. , De Marco G. , Vitti P. , Pinchera A. , Bevilacqua G. , Naccarato A. G. , Viacava P. 
Published: September 2006

SummaryBackground  Iodide (I−) is crucial for foetal thyroid function. Foetal iodide results from maternal circulating iodide and from deiodination of iodothyronines within the placenta. The Na+/I− symporter (NIS) localized in placental cells appears to be involved in iodide exchange. Low NIS expression has been reported in trophoblast cells from the first trimester and pregnancy at term.Aims  The aim of this study was to examine NIS expression by immunohistochemistry in the major components of human ovular tissue and placenta.Materials and methods  Formalin‐fixed and paraffin‐embedded specimens of placental tissue from the first trimester and at term were analysed. NIS expression was quantified as percentage of NIS‐positive cells/total cells. NIS expression was also evaluated by real‐time polymerase chain reaction (RT‐PCR) in five first‐trimester and five at‐term placental specimens.Results  In the first‐trimester specimens heterogeneous NIS immunoreactivity was found in cyto‐syncytiotrophoblast cells, with a range of NIS‐positive cells from 5% to 80% (mean ± SD 21·85 ± 23·95), in mesenchymal and endothelial cells from 1% to 40% (14·5 ± 11·16), in decidual cells from 5% to 40% (10·38 ± 11·98) and in endometrial glands from 3% to 40% (21·86 ± 13·93). In specimens from placenta at term, NIS‐positive cyto‐syncytiotrophoblast cells were between 5% and 40% (mean 17·85 ± 18·15), mesenchymal and endothelial cells between 1% and 40% (13·67 ± 12·16), decidual tissue between 5% and 30% (16·43 ± 9·08), and endometrial glands between 3% and 40% (16·67 ± 15·27). No significant differences in NIS expression were observed between the first trimester and placenta at term. A similar level of mRNA expression for the NIS gene was obtained by RT‐PCR both in ovular material of the first trimester and in placenta at term.Conclusions  We found NIS to be expressed in various placental and ovular components and its expression to remain constant during pregnancy.
Management of amiodarone‐induced thyrotoxicosis in Latin America: an electronic survey
Authors: Diehl Leandro Arthur , Romaldini João Hamilton , Graf Hans , Bartalena Luigi , Martino Enio , Albino Claudio Cordeiro , Wiersinga Wilmar M. 
Published: September 2006

SummaryObjective To assess diagnostic and therapeutic approaches to amiodarone‐induced thyrotoxicosis (AIT) among members of the Latin American Thyroid Society (LATS).Methods LATS members responded to an online questionnaire that presented an index case (a 62‐year‐old man on amiodarone, with thyrotoxic symptoms and a nodular goitre) and a variant (same patient, no goitre).Results About 25% of invited members responded to the questionnaire. Most respondents lived in iodine‐sufficient areas and observed that amiodarone‐induced hypothyroidism (AIH) is more common than AIT. Nearly all assessed TSH, and the most used combination of tests was TSH and free T4 (37%). Thyroid autoimmunity was assessed by about 90%. Interleukin‐6 (IL‐6) was useful to 80%. Additional tests ordered for the index case were: radioactive iodine uptake (RAIU; 57%), echo‐colour Doppler sonography (ECDS; about 50%) and fine‐needle aspiration biopsy (FNAB; 44%). For the variant, ECDS and RAIU were judged unhelpful by 16%. Most defined the index case as type I AIT and the variant as type II AIT, but 16% in LATS suggested a mixed form in the index case. As initial treatment, nearly all used thionamides in the index case [with potassium perchlorate (KClO4) in one‐third], while glucocorticoids were indicated to the variant by 66%. Only about 5% considered amiodarone withdrawal unnecessary. If initial strategy is ineffective in type I AIT, KClO4(half) or glucocorticoids (a third) are added; in type II, glucocorticoids are indicated by most. Once euthyroidism is restored, ablative therapy is prescribed by a third of respondents for type I AIT.Conclusions There are several points of disagreement among thyroidologists regarding AIT management, mainly in the radiological evaluation and the approach to the already stabilized patient if amiodarone needs to be restarted.
11β Hydroxysteroid dehydrogenase type 1 is expressed and is biologically active in human skeletal muscle
Authors: Jang Christina , Obeyesekere Varuni R. , Dilley Rodney J. , Alford Frank P. , Inder Warrick J. 
Published: September 2006

SummaryObjective  No data exist regarding the distribution and oxoreductase enzyme activity of 11β hydroxysteroid dehydrogenase type 1 (11β HSD‐1) in fresh human skeletal muscle. We aimed to investigate the mRNA and protein expression of 11β HSD‐1 in fresh skeletal muscle, confirm its biological activity and determine its relationship with hexose‐6‐phosphate dehydrogenase (H6PDH). We also examined the muscle fibre localization of 11β HSD‐1.Design  Eleven non‐diabetic community volunteers underwent muscle biopsy of vastus lateralis.Measurements  (i) 11β HSD‐1 and H6PDH mRNA expression by quantitative reverse transcription polymerase chain reaction (RT‐PCR); (ii) protein localization and fibre type specificity by immunohistochemistry; and (iii) enzyme oxoreductase activity by percentage conversion of 3H cortisone to cortisol.Results  11β HSD‐1 mRNA was expressed at low levels compared to human liver. Mean ΔCT of skeletal muscle in 11 subjects was 19·57 (range 18·40–20·79) compared to ΔCT of 12·75 in human liver, which equates to an approximate 100‐fold higher level of expression. H6PDH mRNA was also detected with a mean ΔCT of 14·46 (range 13·13–16·60), approximately 35‐fold more abundant than 11β HSD‐1 in skeletal muscle. There was a significant correlation between 11β HSD‐1 and H6PDH (r = 0·67, P = 0·03). 11β HSD‐1 immunostaining was present in all muscle specimens, with similar distribution among fast and slow twitch fibres. 11β HSD‐1 oxoreductase activity was demonstrated, with mean conversion of cortisone to cortisol of 17·7% per 200 mg of muscle per 24 h (range 7·1–29·5%).Conclusions  11β HSD‐1 mRNA and protein is expressed in fresh human skeletal muscle along with readily demonstrable oxoreductase activity. 11β HSD‐1 localization is not muscle fibre type specific. High levels of skeletal muscle H6PDH should ensure that oxoreductase activity predominates in vivo.
Why do female migratory birds arrive later than males?
Authors: KOKKO HANNA , GUNNARSSON TÓMAS G. , MORRELL LESLEY J. , GILL JENNIFER A. 
Published: September 2006

Summary

In migratory birds males tend to arrive first on breeding grounds, except in sex‐role reversed species. The two most common explanations are the rank advantage hypothesis, in which male–male competition for breeding sites drives stronger selection for early arrival in males than females, and the mate opportunity hypothesis, which relies on sexual selection, as early arrival improves prospects of mate acquisition more for males than for females.
To date, theoretical work has focused on selection for early arrival within a single sex, usually male. However, if fitness depends on territory quality, selection for early arrival should operate on both sexes. Here we use two independent modelling approaches to explore the evolution of protandry (male‐first arrival) and protogyny (female‐first arrival) under the rank advantage and mate opportunity hypotheses.
The rank advantage hypothesis, when operating alone, fails to produce consistent patterns of protandry, despite our assumption that males must occupy territories before females. This is because an individual of either sex benefits if it out‐competes same‐sex competitors. Rather than promoting protandry, the rank advantage mechanism can sometimes result in protogyny. Female–female competition is stronger than male–male competition early in the season, if females compete for a resource (territories occupied by males) that is initially less common than the resource of interest to males (unoccupied territories).
Our results support the mate opportunity hypothesis as an explanation of why protandry is the norm in migratory systems. Male‐biased adult sex ratios and high levels of sperm competition (modelled as extra‐pair young: EPY) both produce protandry as a result of sexual selection. Protogyny is only observed in our models with female‐biased sex ratios and low EPY production.
We also show that the effects of sex ratio biases are much stronger than those of EPY production, explore the evidence for sex ratio biases and extra‐pair paternity in migratory species and suggest future research directions.
Density dependence and the control of helminth parasites
Authors: CHURCHER THOMAS S. , FILIPE JOÃO A. N. , BASÁÑEZ MARÍA‐GLORIA 
Published: September 2006

Summary

The transient dynamics and stability of a population are determined by the interplay between species density, its spatial distribution and the positive and negative density‐dependent processes regulating population growth.
Using the human–helminth parasite system as an example, we propose that the life‐stage upon which negative density dependence operates will influence the rate of host reinfection following anthelmintic chemotherapy, and the likely success of control programmes.
Simple deterministic models are developed which highlight how a parasite species whose population size is down‐regulated by density‐dependent establishment will reinfect a host population at a faster rate than a species with density‐dependent parasite fecundity.
Different forms of density dependence can produce the same equilibrium behaviour but different transient dynamics. Under‐representing the nature and magnitude of density‐dependent mechanisms, and in particular those operating upon establishing life‐stages, may cause the resilience of the parasite population to a control perturbation to be underestimated.
The role of group size and environmental factors on survival in a cooperatively breeding tropical passerine
Authors: BROUWER LYANNE , RICHARDSON DAVID S. , EIKENAAR CAS , KOMDEUR JAN 
Published: September 2006

Summary

Variation in survival, a major determinant of fitness, may be caused by individual or environmental characteristics. Furthermore, interactions between individuals may influence survival through the negative feedback effects of density dependence. Compared to species in temperate regions, we have little knowledge about population processes and variation in fitness in tropical bird species.
To investigate whether variation in survival could be explained by population size or climatic variables we used capture–recapture models in conjunction with a long‐term data set from an island population of the territorial, cooperatively breeding Seychelles warbler (Acrocephalus sechellensis). The lack of migration out of the study population means that our results are not confounded by dispersal.
Annual survival was high, both for adults (84%) and juveniles (61%), and did not differ between the sexes. Although there was significant variation in survival between years, this variation could not be explained by overall population size or weather variables.
For territorial species, resource competition will work mainly on a local scale. The size of a territory and number of individuals living in it will therefore be a more appropriate measure of density than overall population density. Consequently, both an index of territory quality per individual (food availability) and local density, measured as group size, were included as individual covariates in our analyses.
Local density had a negative effect on survival; birds living in larger groups had lower survival probabilities than those living in small groups. Food availability did not affect survival.
Our study shows that, in a territorial species, although density‐dependent effects might not be detectable at the population level they can be detected at the individual territory level − the scale at which individuals compete. These results will help to provide a better understanding of the small‐scale processes involved in the dynamics of a population in general, but in particular in tropical species living in relatively stable environments.
Reproductive performance in grey seals: age‐related improvement and senescence in a capital breeder
Authors: BOWEN W. D. , IVERSON S. J. , MCMILLAN J. I. , BONESS D. J. 
Published: September 2006

Summary

Three hypotheses have been advanced to account for age‐related improvement in performance: the selection hypothesis predicts improved due to the loss of lower quality phenotypes, the constraint hypothesis predicts individuals improve function, and the restraint hypothesis predicts younger individuals forego or reduce effort because of mortality risks. A decline in age‐related performance (i.e. senescence) is predicted by mutation accumulation, antagonistic pleiotropy and disposable soma (wear and tear) hypotheses.
Using five measures of performance − birth rate, maternal and pup birth mass, pup weaning mass, weaning success and lactation length − we tested these hypotheses concerning age‐related change in reproduction in 279 female grey seals (Halichoerus grypus), ages 4–42 years, over a 23‐year period between 1983 and 2005 on Sable Island, Nova Scotia. These females produced 2071 pups.
Although body mass of primiparous females increased with age (4–7 years) birth mass of their pups did not, but pup weaning mass did. Second‐ and third‐parity females of the same age as primiparous females gave birth to and weaned heavier pups. However, parity and age were dropped from models when maternal body mass was included.
The proportion of females giving birth varied significantly with maternal age, increasing in young females and then declining late in life. Weaning success rate also increased rapidly to about 8 years and subsequently declined in females > 32 years.
Generalized additive models indicated nonlinear changes in 3 day body mass (i.e. ∼ birth mass) and weaning mass of pups as a function of maternal age, after accounting statistically for the effects of maternal body mass. Mixed‐effects, repeated‐measures models fitted to longitudinal data further supported the conclusion that pup birth mass and weaning mass vary nonlinearly with maternal age and indicated nonlinear changes in lactation duration.
We found some support for the constraint hypothesis, but our findings were not consistent with the selection hypothesis or the restraint hypothesis as the basis for improvement in reproductive performance.
Senescence was evident in multiple female and offspring traits, indicating the degeneration in function of several physiological systems as predicted by the disposable soma hypothesis.