bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐12 p80‐dependent macrophage recruitment primes the host for increased survival following a lethal respiratory viral infection
Authors: Gunsten Sean , Mikols Cassandra L. , Grayson Mitchell H. , Schwendener Reto A. , Agapov Eugene , Tidwell Rose M. , Cannon Carolyn L. , Brody Steven L. , Walter Michael J. 
Published: September 2008

SummaryA protective immune response to a respiratory viral infection requires a series of coordinated cellular and molecular responses. We have previously demonstrated that increased expression of airway epithelial cell interleukin (IL)‐12 p80, a macrophage chemoattractant, is associated with human respiratory viral infection and mediates post‐viral mortality in the mouse. To better understand the role of IL‐12 p80‐dependent macrophage chemotaxis in mediating viral immunity, we generated a transgenic mouse strain utilizing a promoter to drive IL‐12 p40 gene expression in the airway epithelium. This transgenic strain secreted biologically active IL‐12 p80 in a lung‐specific manner, and demonstrated a selective increase in the number of resident, unactivated airway macrophages at baseline. Following infection with a sublethal dose of mouse parainfluenza virus type 1 (Sendai virus), the transgenic mice demonstrated an earlier peak and decline in the number of airway inflammatory cells. The transgenic mice were resistant to a lethal dose of virus and this viral resistance was dependent on the increased number of airway macrophages at baseline as partial depletion prior to infection abrogated this phenotype. The survival advantage in the transgenic mice was independent of viral load but was associated with a more rapid decline in the number of airway inflammatory cells and concentrations of multiple chemokines including the CC chemokine ligand 2 (CCL2)/JE, CCL3/macrophage inflammatory protein (MIP)‐1α, CCL4/MIP‐1β, and CCL5/RANTES. Collectively, these results suggest that IL‐12 p80‐driven increases in the number of resident airway macrophages prime the host for a protective immune response that can confer increased survival following a lethal respiratory viral infection.
The impact of androgen receptor polymorphism and parental ethnicity on semen quality in young men from Latvia
Authors: Erenpreiss J. , Tsarev I. , Giwercman A. , Giwercman Y. 
Published: September 2008

SummaryRecent studies on young men from the general population have demonstrated geographic and ethnic differences in semen quality. The aim of this study was to investigate whether reported ethnic differences in semen quality might be associated with the maternally derived CAG and GGN polymorphisms in the androgen receptor gene or paternal ethnicity. In total 114 military conscripts from Latvia were included in the study. Information on maternal and parental ethnicity was collected by questionnaires. CAG and GGN repeats were analysed by direct sequencing of leukocyte DNA. Men with Latvian mothers (n = 83) had marginally shorter CAG repeat length (21.6 ± 2.9) as compared with those with non‐Latvian mothers (22.9 ± 3.2,n = 31), not reaching statistical significance (p = 0.053). Sperm concentration did not differ significantly between these two groups (76 ± 59 and 70 ± 52,p = 0.9 respectively). In contrast, significantly higher sperm concentration and total sperm count were found in men with Latvian fathers (n = 77) as compared with men with non‐Latvian fathers (n = 37) (80 ± 61 vs. 62 ± 48,p = 0.035, for sperm concentration and 225.7 ± 209 vs. 158.4 ± 134.4,p = 0.002, for total sperm count respectively). CAG repeat length did not correlate with any semen parameters in the whole population. However, GGN repeat length correlated with semen volume: men with GGN > 23 presented with higher semen volume (3.2 ± 2.1) as compared with men with GGN = 23 (2.6 ± 1.3,p = 0.04) or GGN < 23 (2.0 ± 1.2,p = 0.006). We conclude that GGN repeat length has an impact on semen volume, whereas differences in sperm numbers are associated with the paternal ethnicity.
Development of parent–nurse relationships in neonatal intensive care units – from closeness to detachment
Authors: Fegran Liv , Fagermoen May Solveig , Helseth Sølvi 
Published: September 2008

AbstractTitle.  Development of parent–nurse relationships in neonatal intensive care units – from closeness to detachment Aim.  This paper is a report of a study to explore the development of relationships between parents and nurses in a neonatal intensive care unit.Background.  As increasingly smaller premature babies survive, the prolonged hospitalization that follows makes relationships between parents and nurses crucial. A collaborative partnership in which all the family members’ needs are acknowledged is suggested as the best approach.Method.  A hermeneutic approach was adopted, using overt participant observation (160 hours) and in‐depth interviews to study interactions between parents and nurses. The participants were six mothers, six fathers, and six nurses from a 13‐bed Norwegian neonatal intensive care unit. Data were obtained over 27 weeks from 2003 until 2004.Findings.  A partnership between parents and nurses developed in three phases: the acute critical phase, the stabilizing phase, and the discharge phase. The stabilizing phase seemed the most challenging. As exhausted parents expressed the importance of maintaining the trusting relationship with their primary nurses to become confident when assuming more responsibility and adjusting to the new situation, nurses purposely withdrew and reduced their contact with parents, facilitating their independence and confidence as caretakers. Parents and nurses rarely seemed to discuss with each other the discrepancy in their understanding of the detachment process.Conclusion.  Acknowledging the need for parents and nurses to discuss the processes of involvement and detachment may contribute positively to the development of family‐centred care in neonatal intensive care units.
Low PAI‐1 activity in relation to inflammatory parameters, insulin profile and body mass index
Authors: Ågren A. , Wiman B. , Schulman S. 
Published: September 2008

Abstract.Background and objective.  High plasminogen activator inhibitor type 1 (PAI‐1) activity is associated with inflammatory reactions and insulin resistance, but it is unclear what regulates PAI‐1 activity at the low end. The purpose of this study was to investigate if patients with low PAI‐1 activity have a lack of inflammatory response or a low insulin level.Design.  Retrospective cohort study with internal controls.Subjects.  Sixty‐three patients referred for investigation of bleeding tendency and with low PAI‐1 activity were compared with 118 patients with normal or high PAI‐1 activity.Outcome.  Levels of C‐peptide, proinsulin, high‐sensitivity C‐reactive protein (hs‐CRP) and interleukin‐6 (IL‐6). Adjustments were made for body mass index (BMI), oral oestrogens and age. Low PAI‐1 activity was defined as less than 1 U mL−1.Results.  Body mass index in the low normal range, oral oestrogens, young age and low C‐peptide were significantly associated with low PAI‐1 activity and there was a trend for association with IL‐6 in univariable analysis. The effect of age disappeared after correction for oral oestrogens and the effect of C‐peptide and IL‐6 disappeared after further adjustments. Low BMI remained as the strongest predictor of low PAI‐1 activity.Conclusion.  Patients with bleeding tendency and low PAI‐1 activity have inflammatory and insulin profiles similar to those with normal or high PAI‐1, whereas BMI seems to be the most important determinant.
Specific IgE serum concentration is associated with symptom severity in children with seasonal allergic rhinitis
Authors: Rolinck‐Werninghaus C. , Keil T. , Kopp M. , Zielen S. , Schauer U. , Von Berg A. , Wahn U. , Hamelmann E. ,   the Omalizumab Rhinitis Study Group
Published: September 2008

Background:  The impact of allergen‐specific and total IgE serum levels before and during the pollen season on symptom severity as well as efficacy of treatment with anti‐IgE requires further delineation.Methods:  Birch and grass pollen allergic patients aged 6–17 years with seasonal allergic rhinitis (SAR) were analyzed for the association of IgE serum concentration with symptom severity and rescue medication use (combination: symptom load, SL) during the grass pollen season. Reference group A (n = 53) received placebo, while group B (n = 54) received Omalizumab (anti‐IgE) monotherapy before and during the grass pollen season.Results:  Patients on placebo with high baseline specific grass pollen IgE (>50 kU/l) had a significantly higher SL compared with those with low IgE levels (≤50 kU/l): SL 1.28 vs 0.61, P = 0.015. This association was nonexistent in patients treated with anti‐IgE. In contrast, baseline total IgE levels did not correlate with SL in any group. Patients with anti‐IgE treatment and high free total IgE levels (>16.7 ng/ml) had a significantly higher SL compared with those with low free total IgE levels (≤16.7 ng/ml): SL 0.63 vs 0.23, P = 0.031.Conclusions:  Baseline specific IgE, but not total IgE, is associated with symptom severity during the pollen season in children with SAR. Likewise, the symptom load in SAR patients with anti‐IgE correlates with free total IgE levels. Although further research in larger populations is needed to confirm our findings, our data suggest that specific IgE can be used as a parameter for patient selection for this kind of treatment.
Indices of lower airway inflammation in children monosensitized to house dust mite after nasal allergen challenge
Authors: Inal A. , Kendirli S. G. , Yilmaz M. , Altintas D. U. , Karakoc G. B. , Erdogan S. 
Published: September 2008

Background:  There are few available data assessing the united airway disease and its systemic aspects in children. With this study, we aimed to investigate the inflammation markers of upper and lower airways before and after nasal allergen challenge in mite sensitive children with different clinical expression of the allergic disease.Methods:  Four study groups were formed: rhinitis only, without bronchial hyper‐responsiveness (R, n = 10), rhinitis with asthma (R + A, n = 22), atopic asymptomatics (AA, n = 8) and nonallergic healthy controls (C, n = 10). Blood eosinophils, nasal and sputum eosinophils, sputum eosinophil cationic protein (ECP) and cys‐LTs, and serum ECP levels were measured before and 24 h after nasal allergen challenge.Results:  The groups were comparable in terms of age and gender. Cumulative symptom scores recorded during and 1 h after nasal challenge were not significantly different between patients with R, R + A and AA groups. At T24, the children belonging to R, R + A and AA showed significant increases in nasal eosinophils (P < 0.01, P < 0.001, and P = 0.01, respectively), sputum eosinophils (P = 0.01, P < 0.001, and P < 0.05, respectively) and blood eosinophils (P < 0.01, P < 0.001, and P < 0.05, respectively). Similarly, increases in sputum ECP (P < 0.01, P < 0.001, and P = 0.07, respectively) and sputum cys‐LT levels (P = 0.07, P < 0.001, and P < 0.05, respectively) were detected in children belonging to these three groups at T24. Sputum eosinophils significantly correlated with blood eosinophils (r = 0.54, P < 0.001) and sputum ECP (r = 0.58, P < 0.001) at T24.Conclusions:  This study showed that nasal allergen challenge increased markers of eosinophilic inflammation in both upper and lower airways of children monosensitized to mites, even before the onset of clinical symptoms.
Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response
Authors: Rondón C. , Doña I. , López S. , Campo P. , Romero J. J. , Torres M. J. , Mayorga C. , Blanca M. 
Published: September 2008

Background:  Patients with idiopathic rhinitis (IR) are considered to be nonallergic because they have a negative skin prick test (SPT) and allergen specific‐IgE in serum. The concept of localized mucosal allergy in the absence of atopy has recently been proposed. The immunological mechanisms involved in seasonal IR have not been sufficiently studied. We examined nasal mucosa inflammation, the presence of nasal specific‐IgE and the response to nasal allergen provocation test (NAPT) in patients with seasonal IR who presented symptoms only in spring.Methods:  We evaluated 32 patients with seasonal IR and 35 with persistent allergic rhinitis to pollen (PAR‐P) and compared these with healthy controls and persons with PAR to house dust mite during the pollen season, as well as by NAPT out‐of‐season with grass and Olea europea. We measured the nasal leukocyte–lymphocyte phenotype (CD45, CD33, CD16, CD3, CD4 and CD8), eosinophil‐cationic‐protein, and total and specific‐IgE to grass and olive pollen in serum and nasal lavage and performed NAPT.Results:  In the IR group, 62.5% had a positive NAPT (IR‐PosNAPT), 20/32 to grass, with four of these having a positive NAPT to olive pollen as well. IR‐PosNAPT patients showed a similar nasal leukocyte–lymphocyte profile to the PAR‐P patients and different to controls. We detected nasal specific‐IgE in 35% of IR‐PosNAPT patients.Conclusions:  These results support the hypothesis that a subgroup of patients with IR have seasonal symptoms with evidence of a nasal allergic immune reaction in the absence of a positive SPT or serum specific IgE.
Histamine H4receptors modulate dendritic cell migration through skin – immunomodulatory role of histamine
Authors: Bäumer W. , Wendorff S. , Gutzmer R. , Werfel T. , Dijkstra D. , Chazot P. , Stark H. , Kietzmann M. 
Published: September 2008

Background: Dendritic cells (DC) are the major antigen‐presenting cells and play a key role in adaptive immunity as they are able to activate naive T cells. It was recently described, that the histamine H4receptor (H4R) is present on human monocyte‐derived DC and that chemotaxis and T‐helper (Th)1–Th2 polarization is mediated by this receptor. However, the distribution of histamine receptors on murine DC has not been studied yet.Methods: The histamine receptor expression on murine bone marrow (BM)‐derived DC and effects of histamine and H4R agonism on DC migration through skin were studied. As it was demonstrated in scratching experiments that NMRI mice are more susceptible to H4R‐mediated itch than BALB/c mice, DC function of NMRI and BALB/c mice was compared.Results: The mRNA of the H1R, H2R and H4R could be detected in murine BM‐derived DC, while mRNA of the H3R was found to be low or undetectable. There were no distinct differences in mRNA expression and in H4R protein level (flow cytometry) between NMRI compared with BALB/c mice indicating, that a higher susceptibility is not associated with a generally higher H4R expression in all cell types. Histamine as well as the H4R agonist clobenpropit induced an enhanced chemotaxis in the skin DC migration assay. The enhanced chemotaxis was blocked by the H4R antagonist JNJ7777120. This finding was confirmed byin vitromigration experiments with BM‐derived DC.Conclusion: Referring to DC migration, blocking the H4R on inflammatory cells might be a promising anti‐inflammatory, immunomodulatory strategy.
Mediterranean diet is associated with reduced asthma and rhinitis in Mexican children
Authors: De Batlle J. , Garcia‐Aymerich J. , Barraza‐Villarreal A. , Antó J. M. , Romieu I. 
Published: September 2008

Background:  Diet during pregnancy and childhood has been suggested to play an important role in children’s asthma risk. We assessed whether the adherence to a Mediterranean dietary pattern, for children in the last 12 months and their mothers during pregnancy, was associated with both childhood asthma and allergic rhinitis.Methods:  A cross‐sectional study was conducted in 2004 using a random sample of 1476 children (6‐ to 7‐year old) from the Mexicali region, Mexico. Dietary data of children’s intake in the last 12 months and their mothers’ intake during pregnancy was collected, through a parental food frequency questionnaire. A Mediterranean diet score was computed [Trichopoulou et al., N Engl J Med 348 (2003), 2599]. Data on seven asthma and rhinitis‐related outcomes were obtained from the International Study of Asthma and Allergies in Childhood questionnaire.Results:  Adherence to a Mediterranean dietary pattern was inversely associated with asthma ever (OR = 0.60, 95% CI = 0.40–0.91), wheezing ever (0.64, 0.47–0.87), rhinitis ever (0.41, 0.22–0.77), sneezing ever (0.79, 0.59–1.07), current sneezing (0.71, 0.52–0.96) and current itchy‐watery eyes (0.63, 0.42–0.95). No associations were found using the mothers’ pregnancy diet score, except for current sneezing (0.71, 0.53–0.97).Conclusions:  Our findings suggest a protective effect of following a healthy dietary pattern on asthma and allergic rhinitis in Mexican children.
Soluble HLA‐G and HLA‐A,‐B,‐C serum levels in patients with allergic rhinitis
Authors: Ciprandi G. , Colombo B. M. , Contini P. , Cagnati P. , Pistorio A. , Puppo F. , Murdaca G. 
Published: September 2008

Background:  Allergic rhinitis (AR) is characterized by Th2‐polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. So far, however, no study investigated them in AR.Objective:  The aim of this study was to evaluate sHLA‐G and sHLA‐A,‐B,‐C serum levels in AR patients with pollen allergy and in a group of healthy controls.Methods:  Forty‐nine AR patients were enrolled. A group of healthy nonallergic subjects was considered as control. sHLA‐G and sHLA‐A,‐B,‐C serum levels were determined by immunoenzymatic method. The study was conducted during the winter, such as outside the pollen season.Results:  Allergic patients had significantly higher levels of both sHLA‐G (P < 0.0001) and sHLA‐A,‐B,‐C (P = 0.011) molecules than normal controls. Moreover, there was a significant relationship between these two soluble molecules (r = 0.69) in allergic patients.Conclusion:  The present study provides the first evidence that both sHLA‐G and sHLA‐A,‐B,‐C serum levels are significantly increased in AR patients with pollen allergy.
New oral H1 antihistamines in children: facts and unmeet needs
Authors: De Benedictis F. M. , De Benedictis D. , Canonica G. W. 
Published: September 2008

Background:  Second‐generation antihistamines differ from first‐generation ones because of their elevated specificity and affinity for peripheral H1‐receptors and because of their lower penetration to the central nervous system, having fewer sedative effects as a result. Over the last few years, new compounds with different pharmacokinetic properties have been synthesized. More recent improvements of the molecules, generally in the form of active metabolites, led to the synthesis of new‐generation antihistamines.Methods:  Recommendations on the minimum criteria that would have to be met for compounds to be classified as new‐generation antihistamines have been recently established by a consensus statement. In the past, the pharmacokinetics and pharmacodynamics of H1 antihistamines have not been optimally investigated in the pediatric population, especially in infants and young children.Results:  The pharmacology of second‐generation H1 antihistamines has been investigated relatively deeper than old antihistamines in children. In the pediatric population, clinical studies with new‐generation antihistamines are still limited in number and, with rare exceptions, of brief duration. Comparative trials on the efficacy and safety between different compounds are also lacking.Conclusions:  Properly designed, long‐term trials with new‐generation H1 antihistamines need to be performed in single age groups, in order to better define the effects of these drugs in all pediatric population.
Alterations of the ocular surface epithelial MUC16 and goblet cell MUC5AC in patients with atopic keratoconjunctivitis
Authors: Dogru M. , Matsumoto Y. , Okada N. , Igarashi A. , Fukagawa K. , Shimazaki J. , Tsubota K. , Fujishima H. 
Published: September 2008

Background:  An increased understanding of the ocular surface at cellular level in the conjunctiva and the cornea may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding.Purpose:  To investigate the MUC16 and MUC5AC alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis (AKC).Methods:  Thirty‐six eyes of 18 AKC patients as well as 28 eyes of 14 age‐ and sex‐matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break‐up time (BUT), fluorescein and Rose‐Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid schiff and immunohistochemical staining with MUC16 and MUC5AC antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real‐time polymerase chain reaction (PCR) for MUC16 and MUC5AC mRNA expression.Results:  The mean corneal sensitivity and BUT values were significantly lower in patients with AKC, compared with controls (P < 0.001). Brush cytology specimens from AKC patients revealed significantly higher numbers of inflammatory cells (P < 0.001). Specimens from patient eyes showed positive staining for MUC5AC and MUC16. MUC16 mRNA expression was significantly upregulated with significant downregulation of MUC5AC mRNA expression in eyes with AKC compared with the eyes of control subjects.Conclusion:  Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC5AC and MUC16 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.
n‐Nonanoyl‐CCL14 (NNY‐CCL14), a novel inhibitor of allergic airway inflammation is a partial agonist of human CCR2
Authors: Gupta S. , Erdmann G. , Schulz‐Maronde S. , Escher S. E. , Richter R. , Forssmann W. G. , Elsner J. , Forssmann U. 
Published: September 2008

Background: Modulation of leukocyte recruitment through blocking of chemokine receptors has been proposed as an attractive therapeutic strategy. We have previously demonstrated thatn‐Nonanoyl‐CC chemokine ligand 14 (NNY‐CCL14), a modified analog of the naturally occurring chemokine CCL14(9‐74) internalizes and desensitizes human CCR3 resulting in the inactivation of eosinophils. However, inhibitory effects of NNY‐CCL14 in murine models of allergic airway inflammation are assigned to its interaction with CCR1 and CCR5.Aim of the study: As CCL2 and its receptor CCR2 have been shown to play important roles in the development of Th2 inflammation, we further evaluated the effects of NNY‐CCL14 treatment on CCL2‐mediated activation of CCR2.Methods: Effects of NNY‐CCL14 treatment were studied on cell lines transfected with human CCR2 and primary leukocytes. Functional effects were assessed by calcium efflux assays, flow cytometry and chemotaxis.Results: Prestimulation with NNY‐CCL14 desensitized CCR2‐mediated responses to further stimulation with its selective ligand CCL2. No significant internalization of CCR2 was observed when the cells were stimulated with NNY‐CCL14, even at concentrations eliciting maximal [Ca2+]i mobilization. Above all, NNY‐CCL14 pretreatment blocked CCL2‐induced chemotaxis of monocytes.Conclusions: This study demonstrates that NNY‐CCL14 is a partial agonist of CCR2, inhibiting responses of monocytes to the CCR2‐selective ligand CCL2. NNY‐CCL14 attenuates CCR2‐mediated responses by rapidly desensitizing the receptor and preventing chemotaxis, although it is able to induce calcium mobilization but does not lead to CCR2 internalization. Hence this study provides further insights into the possible mechanisms of action of NNY‐CCL14, which interacts with multiple chemokine receptors inhibiting the migration and activation of different cell populations involved, thus acting as a potential therapeutic compound to alleviate allergic inflammation.