bluuebunny/crossref_metadata_2025 huggingface dataset:
A short treatment of cells with the lanthanide ions La3+, Ce3+, Pr3+ or Nd3+ changes the cellular chemistry into a state in which RNA replication of flaviviruses is specifically blocked without interference with host-cell multiplication
Authors: Wengler Gerd , Wengler Gisela , Koschinski Andreas
Published: October 2007

Alpha- and flaviviruses contain class II fusion proteins, which form ion-permeable pores in the target membrane during virus entry. The pores generated during entry of the alphavirus Semliki Forest virus have been shown previously to be blocked by lanthanide ions. Here, analyses of the influence of rare earth ions on the entry of the flaviviruses West Nile virus and Uganda S virus revealed an unexpected effect of lanthanide ions. The results showed that a 30 s treatment of cells with an appropriate lanthanide ion changed the cellular chemistry into a state in which the cells no longer supported the multiplication of flaviviruses. This change occurred in cells treated before, during or after infection, did not inhibit multiplication of Semliki Forest virus and did not interfere with host-cell multiplication. The change was generated in vertebrate and insect cells, and was elicited in the presence of actinomycin D. In vertebrate cells, the change was elicited specifically by La3+, Ce3+, Pr3+ and Nd3+. In insect cells, additional lanthanide ions had this activity. Further analyses showed that lanthanide ion treatment blocked the ability of the host cell to support the replication of flavivirus RNA. These results open two areas of research: the study of molecular alterations induced by lanthanide ion treatment in uninfected cells and the analysis of the resulting modifications of the flavivirus RNA replicase complex. The findings possibly open the way for the development of a general chemotherapy against flavivirus diseases such as Dengue fever, Japanese encephalitis, West Nile fever and yellow fever.
Full-length genome sequences of hepatitis C virus subtype 4f
Authors: Hmaied Fatma , Legrand-Abravanel Florence , Nicot Florence , Garrigues Natalie , Chapuy-Regaud Sabine , Dubois Martine , Njouom Richard , Izopet Jacques , Pasquier Christophe
Published: October 2007

Hepatitis C virus genotype 4 (HCV-4) is very common in central Africa, prevalent in the Middle East, and is becoming increasingly frequent among southern Europeans. We have determined the complete nucleotide sequences of HCV-4f strains and investigated their phylogenetic relationships with other genotypes. We amplified the complete genome of two HCV subtype 4f strains, IFBT84 and IFBT88. The HCV-4f strains have a total of 9181 and 9304 nt, respectively, including the 5′ untranslated region followed by a single open reading frame. There was no evidence of genomic recombination in the IFBT84 and IFBT88 strains. The sequences of the HCV-4f strain genomes are closer to those of HCV-1b than to genotypes 2, 3, 5 and 6. It is important to know the full-length sequences of HCV-4 subtypes in order to classify them correctly and to obtain more detailed knowledge about HCV epidemiology and sensitivity to interferon.
Reduction of phospholipase D activity during coxsackievirus infection
Authors: Duijsings Daniël , Wessels Els , van Emst-de Vries Sjenet E. , Melchers Willem J. G. , Willems Peter H. G. M. , van Kuppeveld Frank J. M.
Published: October 2007

During enterovirus infection, host cell membranes are rigorously rearranged and modified. One ubiquitously expressed lipid-modifying enzyme that might contribute to these alterations is phospholipase D (PLD). Here, we investigated PLD activity in coxsackievirus-infected cells. We show that PLD activity is not required for efficient coxsackievirus RNA replication. Instead, PLD activity rapidly decreased upon infection and upon ectopic expression of the viral 3A protein, which inhibits the PLD activator ADP-ribosylation factor 1. However, similar decreases were observed during infection with coxsackieviruses carrying defective mutant 3A proteins. Possible causes for the reduction of PLD activity and the biological consequences are discussed.
Enhanced polymerase activity confers replication competence of Borna disease virus in mice
Authors: Ackermann Andreas , Kugel Daniela , Schneider Urs , Staeheli Peter
Published: October 2007

We previously showed that mouse adaptation of cDNA-derived Borna disease virus (BDV) strain He/80FR was associated exclusively with mutations in the viral polymerase complex. Interestingly, independent mouse adaptation of non-recombinant He/80 was correlated with different alterations in the polymerase and mutations in the viral glycoprotein. We used reverse genetics to demonstrate that changes in the polymerase which improve enzymatic activity represent the decisive host range mutations. The glycoprotein mutations did not confer replication competence in mice, although they slightly improved viral performance if combined with polymerase mutations. Our findings suggest that the viral polymerase restricts the host range of BDV.
Two functionally linked amino acids in the stem 2 region of measles virus haemagglutinin determine infectivity and virulence in the rodent central nervous system
Authors: Moeller-Ehrlich K. , Ludlow M. , Beschorner R. , Meyermann R. , Rima B. K. , Duprex W. P. , Niewiesk S. , Schneider-Schaulies J.
Published: October 2007

Rodent brain-adapted measles virus (MV) strains, such as CAM/RB and recombinant MVs based on the Edmonston strain containing the haemagglutinin (H) of CAM/RB, cause acute encephalitis after intracerebral infection of newborn rodents. We have demonstrated that rodent neurovirulence is modulated by two mutations at amino acid positions 195 and 200 in the H protein, one of these positions (200) being a potential glycosylation site. In order to analyse the effects of specific amino acids at these positions, we introduced a range of individual and combined mutations into the open reading frame of the H gene to generate a number of eukaryotic expression plasmids. The functionality of the mutant H proteins was assessed in transfected cells and by generating recombinant viruses. Interestingly, viruses caused acute encephalitis only if the amino acid Ser at position 200 was coupled with Gly at position 195, whereas viruses with single or combined mutations at these positions, including glycosylation at position 200, were attenuated. Neurovirulence was associated with virus spread and induction of neuronal apoptosis, whereas attenuated viruses failed to infect brain cells. Similar results were obtained by using primary brain-cell cultures. Our findings indicate that a structural alteration in the stem 2 region of the H protein at position 195 or 200 interferes with infectivity of rodent neurons, and suggest that the interaction of the viral attachment protein with cellular receptors on neurons is affected.
Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential
Authors: Wong Piu , Iwasaki Masayuki , Somervaille Tim C.P. , So Chai Wai Eric , Cleary Michael L.
Published: October 2007

Oncogenic mutations of the MLL histone methyltransferase confer an unusual ability to transform non-self-renewing myeloid progenitors into leukemia stem cells (LSCs) by mechanisms that remain poorly defined. Misregulation of Hox genes is likely to be critical for LSC induction and maintenance but alone it does not recapitulate the phenotype and biology of MLL leukemias, which are clinically heterogeneous—presumably reflecting differences in LSC biology and/or frequency. TALE (three-amino-acid loop extension) class homeodomain proteins of the Pbx and Meis families are also misexpressed in this context, and we thus employed knockout, knockdown, and dominant-negative genetic techniques to investigate the requirements and contributions of these factors in MLL oncoprotein-induced acute myeloid leukemia. Our studies show that induction and maintenance of MLL transformation requires Meis1 and is codependent on the redundant contributions of Pbx2 and Pbx3. Meis1 in particular serves a major role in establishing LSC potential, and determines LSC frequency by quantitatively regulating the extent of self-renewal, differentiation arrest, and cycling, as well as the rate of in vivo LSC generation from myeloid progenitors. Thus, TALE proteins are critical downstream effectors within an essential homeoprotein network that serves a rate-limiting regulatory role in MLL leukemogenesis.
Integrating Naval Aviation Maintenance Training with Sailors' Proficiency Qualification and Its Correlation with Improved Weapon System Readiness
Authors: SNOW JOHN P. , ROSS JAMES M. , BERKIN MICHAEL G. , BOSCHEN EDWARD D.
Published: October 2007

A core role for human systems integration is providing support of weapon systems operational effectiveness with optimal human performance (HP). When applied to the readiness of an aviation squadron, this focus on enhanced operational HP translates into ensuring that highly trained and proficient maintenance technicians are resident in these warfighting units. A key objective of the Naval Aviation Enterprise (NAE) Total Force Readiness program is to bridge Core Capabilities to Missions. This is accomplished through the linking of Navy Mission Essential Task Lists (NMETLs) to Skill Sets and Performance Standards for its future workforce. These goals can be accomplished from Initial Development to Deployment of a weapons system through its operational and support phases of the Department of Defense acquisition process using a mission/task‐centric approach to Manpower, Personnel, and Training (MPT) requirements, with NMETLs as the operational thread. This paper will describe a life‐cycle MPT analytic environment with its task‐level links to systems and human engineering disciplines. A systematic approach to accessing and training a proficient maintenance workforce is presented, focusing on task‐based maintenance training solutions for optimal unit readiness and mission capabilities. An innovative analytic framework from various skills‐based manpower analysis studies will be cited as a means to transform system and unit MPT performance for Total Force Readiness. Enhanced by a Qualified and Proficient Technician methodology, a capability (missions) and competency (proficient) future workforce with skills‐efficient maintainers will be best suited to achieving optimal readiness of weapons systems within the NAE.
Human Performance Measurement: Cultural Changes
Authors: HUGHES GEORGE , DAVIDSON KAROLE
Published: October 2007

There has been a high degree of cooperation and collaboration among the Navy system commands with respect to human performance under the Human Systems Performance Assessment Capability initiative. Additionally, the various warfare centers for Naval Sea Systems Command have shown the ability to team across the wide Navy organization. The steering group has shown the practitioners how to team and work together to accomplish similar objectives across different systems. Opportunities to collaborate have been identified and executed with minimal supervision and measurable contributions have been collected. One of the valuable benefits that has been gained through this effort is the ability for practitioners to share knowledge, methods, and tools with their counterparts across the Navy infrastructure. A shared common approach to addressing human performance data collection is emerging as a result. One of the real advantages of the project is a shared vision on the importance of human performance as part of the system engineering process of defining requirements through the eventual test and evaluation phases of a program.
Multilocus ribosomal RNA phylogeny of the leaf beetles (Chrysomelidae)
Authors: Gómez‐Zurita Jesús , Hunt Toby , Vogler Alfried P.
Published: October 2007

Basal relationships in the Chrysomelidae (leaf beetles) were investigated using two nuclear (small and partial large subunits) and mitochondrial (partial large subunit) rRNA (≈ 3000 bp total) for 167 taxa covering most major lineages and relevant outgroups. Separate and combined data analyses were performed under parsimony and model‐based tree building algorithms from dynamic (direct optimization) and static (Clustal and BLAST) sequence alignments. The performance of methods differed widely and recovery of well established nodes was erratic, in particular when using single gene partitions, but showed a slight advantage for Bayesian inferences and one of the fast likelihood algorithms (PHYML) over others. Direct optimization greatly gained from simultaneous analysis and provided a valuable hypothesis of chrysomelid relationships. The BLAST‐based alignment, which removes poorly aligned sequence segments, in combination with likelihood and Bayesian analyses, resulted in highly defensible trees obtained in much shorter time than direct optimization, and hence is a viable alternative when data sets grow. The main taxonomic findings include the recognition of three major lineages of Chrysomelidae, including a basal “sagrine” clade (Criocerinae, Donaciinae, Bruchinae), which was sister to the “eumolpine” (Spilopyrinae, Eumolpinae, Cryptocephalinae, Cassidinae) plus “chrysomeline” (Chrysomelinae, Galerucinae) clades. The analyses support a broad definition of subfamilies (i.e., merging previously separated subfamilies) in the case of Cassidinae (cassidines + hispines) and Cryptocephalinae (chlamisines + cryptocephalines + clytrines), whereas two subfamilies, Chrysomelinae and Eumolpinae, were paraphyletic. The surprising separation of monocot feeding Cassidinae (associated with the eumolpine clade) from the other major monocot feeding groups in the sagrine clade was well supported. The study highlights the need for thorough taxon sampling, and reveals that morphological data affected by convergence had a great impact when combined with molecular data in previous phylogenetic analyses of Chrysomelidae.

© The Willi Hennig Society 2007.
Incorporation of gap characters and lineage‐specific regions into phylogenetic analyses of gene families from divergent clades: an example from the kinesin superfamily across eukaryotes
Authors: Simmons Mark P. , Richardson Dale , Reddy Anireddy S. N.
Published: October 2007

The kinesin superfamily across eukaryotes was used to examine how incorporation of gap characters scored from conserved regions shared by all members of a gene family and incorporation of amino acid and gap characters scored from lineage‐specific regions affect gene‐tree inference of the gene family as a whole. We addressed these two questions in the context of two different densities of sequence sampling, four alignment programs, and two methods of tree construction. Taken together, our findings suggest the following. First, gap characters should be incorporated into gene‐tree inference, even for divergent sequences. Second, gene regions that are not conserved among all or most sequences sampled should not be automatically discarded without evaluation of potential phylogenetic signal that may be contained in gap and/or sequence characters. Third, among the four alignment programs evaluated using their default alignment parameters, Clustal may be expected to output alignments that result in the greatest gene‐tree resolution and support. Yet, this high resolution and support should be regarded as optimistic, rather than conservative, estimates. Fourth, this same conclusion regarding resolution and support holds for Bayesian gene‐tree analyses relative to parsimony‐jackknife gene‐tree analyses. We suggest that a more conservative approach, such as aligning the sequences using DIALIGN‐T or MAFFT, analyzing the appropriate characters using parsimony, and assessing branch support using the jackknife, is more appropriate for inferring gene trees of divergent gene families.

© The Willi Hennig Society 2007.
IPO Underpricing and Audit Quality Differentiation within Non‐Big 5 Firms
Authors: Albring Susan M. , Elder Randal J. , Zhou Jian
Published: October 2007

The choice of a non‐Big 5 audit firm is optimal for some IPO companies. The choice of audit firm is important because auditor reputation may influence the pricing of the offering. This paper investigates the relationship between IPO underpricing and auditor compensation and proxies for non‐Big 5 audit quality. We develop a continuous measure of auditor reputation based on factor analysis. This measure of auditor reputation is associated with lower IPO underpricing and higher auditor compensation, suggesting that auditor quality is an important determinant for firms hiring non‐Big 5 auditors. We also examine the underlying constructs for auditor quality to determine their separate effects on IPO underpricing and auditor quality. Non‐Big 5 national firms are associated with lower underpricing and higher auditor compensation, suggesting that these firms are perceived to be quality differentiated from non‐national firms. SEC experience for non‐national firms is associated with higher audit fees, suggesting this experience is perceived to be valuable.
Involvement of kinesin family member 2C/mitotic centromere‐associated kinesin overexpression in mammary carcinogenesis
Authors: Shimo Arata , Tanikawa Chizu , Nishidate Toshihiko , Lin Meng‐Lay , Matsuda Koichi , Park Jae‐Hyun , Ueki Tomomi , Ohta Tomohiko , Hirata Koichi , Fukuda Mamoru , Nakamura Yusuke , Katagiri Toyomasa
Published: October 2007

To elucidate the molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out genome‐wide expression profile analysis of 81 breast cancer cases by means of cDNA microarray coupled with laser microbeam microdissection of cancer cells. Among the dozens of transactivated genes, in the present study we focused on the functional significance of kinesin family member 2C (KIF2C)/mitotic centromere‐associated kinesin (MCAK) in the growth of breast cancer cells. Northern blot and immunohistochemical analyses confirmed KIF2C/MCAK overexpression in breast cancer cells, and showed that it is expressed at undetectable levels in normal human tissues except the testis, suggesting KIF2C/MCAK to be a cancer–testis antigen. Western blot analysis using breast cancer cell lines revealed a significant increase in the endogenous KIF2C/MCAK protein level and its phosphorylation in G2/M phase. Treatment of breast cancer cells with small interfering RNA against KIF2C/MCAK effectively suppressed KIF2C/MCAK expression and inhibited the growth of the breast cancer cell lines T47D and HBC5. In addition, we found that KIF2C/MCAK expression was significantly suppressed by ectopic introduction of p53. These findings suggest that overexpression of KIF2C/MCAK might be involved in breast carcinogenesis and is a promising therapeutic target for breast cancers. (Cancer Sci 2008; 99: 62–70)
Osmotic adjustment in three succulent species ofZygophyllaceae
Authors: Kamel M.
Published: October 2007

Three species,Zygophyllum albumL.,Z. coccineumL. andZ. simplexL.,from familyZygophyllaceaewere collected from two locations in Egypt to study their response to environmental conditions. Organic solutes (amino acids, soluble proteins and soluble sugars) and inorganic solutes (Na+, K+, Ca2+, Mg2+, Cl−, PO43−and SO42−) were estimated to study their role in osmotic adjustment under the effect of drought and salinity. The study showed thatZ. coccineumis most tolerant for drought and salinity thanZ. simplex. Z. coccineumwas dependent on soluble proteins and soluble sugars, to increase its content of bound water, to undergo water deficit in desert.Z. simplexaccumulated inorganic solutes more thanZ.coccineumand less organic solutes. Amino acids content increased inZ. coccineumandZ. simplexsurvived in saline conditions to play a role in osmotic adjustment. Under the effect of salinity, all the studied species showed a tendency and high capacity to accumulate inorganic solutes. The main inorganic salutes were Ca2+, Mg2+and Cl−. The role of Na+was less than Ca2+and Mg2+.Z. albumandZ. simplexpreferred Mg2+more thanZ. coccineumwhich preferred Ca2+.
The role of water abundance, thermoregulation, perceived predation risk and interference competition in water access by African herbivores
Authors: Valeix Marion , Fritz Hervé , Matsika Ruwadzano , Matsvimbo Fadzai , Madzikanda Hillary
Published: October 2007

In African savannas, surface water can become limiting and an understanding of how animals address the trade‐offs between different constraints to access this resource is needed. Here, we describe water access by ten African herbivore species in Hwange National Park, Zimbabwe, and we explore four possible determinants of the observed behaviours: water abundance, thermoregulation, perceived predation risk and interference competition. On average, herbivores were observed to drink in 80% of visits to a waterhole. The probability of drinking was higher in 2003 (474 mm) than in 2004 (770 mm), and at the end of the dry season than at its beginning. For larger species, this probability may also be related to risks of interference competition with elephants or other herbivores. For smaller species, this probability may also be related to the perceived risk of predation. We also investigate the time spent accessing water to drink. The influence of herd size and the presence of young on the time spent accessing water for most species suggests that perceived predation risk plays a role. Thermoregulation also affects this time: during the hottest periods, herbivores spend less time in open areas, unless when wind is strong, probably owing to evapotranspired heat loss.
Murine models of chronic lymphocytic leukaemia: role of microRNA‐16 in the New Zealand Black mouse model
Authors: Scaglione Brian J. , Salerno Erica , Balan Murugabaskar , Coffman Frederick , Landgraf Pablo , Abbasi Fatima , Kotenko Sergei , Marti Gerald E. , Raveche Elizabeth S.
Published: October 2007

Mouse models are valuable tools in the study of human chronic lymphocytic leukaemia (CLL). The New Zealand Black (NZB) strain is a naturally occurring model of late‐onset CLL characterized by B‐cell hyperproliferation and autoimmunity early in life, followed by progression to CLL. Other genetically engineered models of CLL that have been developed include (NZB × NZW) F1 mice engineered to expressIL5, mice expressing humanTCL1A, and mice overexpressing bothBCL2and a tumour necrosis factor receptor‐associated factor. The applicability to human CLL varies with each model, suggesting that CLL is a multifactorial disease. Our work with thede novoNZB model has revealed many similarities to the human situation, particularly familial CLL. In NZB, the malignant clones express CD5, zap‐70, and have chromosomal instability and germline Ig sequence. We also identified a point mutation in the 3′‐flanking sequence ofMirn16‐1, which resulted in decreased levels of the microRNA, miR‐16 in lymphoid tissue. Exogenous restoration of miR‐16 to an NZB malignant B‐1 cell line resulted in cell cycle alterations, suggesting that the altered expression ofMirn15a/16‐1is an important molecular lesion in CLL. Future studies utilizing the NZB mouse could ascertain the role of environmental triggers, such as low dose radiation and organic chemicals in the augmentation of a pre‐existing propensity to develop CLL.
The Victoria Climbié case: social work education for practice in children and families' work before and since
Authors: Balen Rachel , Masson Helen
Published: October 2007

Based on their research into the Victoria Climbié Inquiry, the authors outline an analysis they undertook of literature which had made substantial comment on either the inquiry itself and/or the subsequent inquiry report. An overview of 18 publications is provided, with four categories of themes emerging. These themes are outlined and then connected with concerns the authors of the current paper identified in journal papers written 10 years or more ago. It is argued that the gap between recognition that society needs competent, well‐trained and skilled social work and other professionals to safeguard the lives of children and families and understanding of what education, training and employment support mechanisms are necessary in order for workers to become and remain well‐trained, skilled and effective, remains as wide as ever. The paper concludes with an outline of teaching approaches the current authors have adopted in pursuit of the kinds of learning opportunities they believe need to be put in place to improve professional practice in children and families' work. These include creative use of child abuse inquiry reports themselves, role plays and simulations and workshops designed to enhance critical reflection skills.
Getting the complete picture: combining parental and child data to identify the barriers to social inclusion for children living in low socio‐economic areas
Authors: Davies B. , Davis E. , Cook K. , Waters E.
Published: October 2007

Background Childhood mental health problems are prevalent in Australian children (14–20%). Social exclusion is a risk factor for mental health problems, whereas being socially included can have protective effects. This study aims to identify the barriers to social inclusion for children aged 9–12 years living in low socio‐economic status (SES) areas, using both child‐report and parent‐report interviews.

Methods Australian‐born English‐speaking parents and children aged 9–12 years were sampled from a low SES area to participate in semi‐structured interviews. Parents and children were asked questions around three prominent themes of social exclusion; exclusion from school, social activities and social networks.

Results Many children experienced social exclusion at school, from social activities or within social networks. Overall, nine key barriers to social inclusion were identified through parent and child interviews, such as inability to attend school camps and participate in school activities, bullying and being left out, time and transport constraints, financial constraints and safety and traffic concerns. Parents and children often identified different barriers.

Discussion There are several barriers to social inclusion for children living in low SES communities, many of which can be used to facilitate mental health promotion programmes. Given that parents and children may report different barriers, it is important to seek both perspectives.

Conclusion This study strengthens the evidence base for the investments and action required to bring about the conditions for social inclusion for children living in low SES communities.
The involvement of type 1a angiotensin II receptors in the regulation of airway inflammation in a murine model of allergic asthma
Authors: Ohwada K. , Watanabe K. , Okuyama K. , Ohkawara Y. , Sugaya T. , Takayanagi M. , Ohno I.
Published: October 2007

BackgroundThere has been increasing evidence suggesting the involvement of angiotensin II (Ang II) and type 1 Ang II receptors (AT1) in the pathogenesis of bronchial asthma. However, whether such an involvement would promote or suppress the pathophysiology of asthma is controversial.

ObjectiveThe aim of this study was to investigate the role of AT1 in the development of allergic airway inflammation.

MethodsAgtr1a+/+[wild‐type C57BL/6 mice (WT)] andAgtr1a−/−mice [AT1a knockout mice (AT1aKO)] with a genetic background of C57BL/6 were systemically sensitized to ovalbumin (OVA), followed by OVA inhalation. OVA‐specific IgE in serum obtained just before the inhalation was measured. Bronchoalveolar lavage (BAL) fluid and lung tissues were obtained at various time‐points. Cell numbers and differentiation, and cytokine contents in BAL fluids were determined. Peribronchial accumulation of eosinophils and mucus inclusions in the bronchial epithelium were evaluated in lung tissues stained histochemically. Cell numbers and differentiation in BAL fluids of the mice were also determined after lipopolysaccharide (LPS) inhalation.

ResultsThe levels of OVA‐specific IgE in AT1aKO were significantly higher than those in WT. The numbers of total cell, eosinophils and lymphocytes in BAL fluids 7 days after OVA inhalation in AT1aKO were significantly higher than those in WT. Airway inflammation in bronchial tissues in terms of eosinophil accumulation and mucus hypersecretion in AT1aKO was also stronger than in WT. The contents of IL‐4, IL‐5 and IL‐13, but not IFN‐γ, in BAL fluids of AT1aKO were significantly higher than those of WT. In contrast, neutrophil accumulation in BAL fluids after LPS inhalation was significantly higher in WT than in AT1aKO.

ConclusionAT1a might be involved in the negative regulation of the development of allergic airway inflammation through polarizing the T‐helper (Th) balance towards Th1 predominance. Therefore, it would be of clinical importance to investigate the effects of long‐term administration of AT1 blockers on the Th1/Th2 balance in hypertensive patients with bronchial asthma.
Relationship of fish and cod oil intake with adult asthma
Authors: Laerum B. N. , Wentzel‐Larsen T. , Gulsvik A. , Omenaas E. , Gíslason T. , Janson C. , Svanes C.
Published: October 2007

Background
A diet rich in fish or cod oil might possibly reduce the risk for asthma and atopic diseases. However, previous studies show conflicting results and no studies have assessed the potential long‐term effects of childhood fish intake on adult asthma.

Objective
To investigate whether childhood and adult fish and cod oil intake was related to adult asthma.

Methods
In a large population‐based study, Respiratory Health in Northern Europe (RHINE), 16 187 subjects aged 23–54 years answered a postal questionnaire. The relations of fish and cod oil intake with asthma symptoms and asthma were analysed using multiple logistic and Cox regression analyses, with adjustment for gender, adult hayfever, smoking, age, body mass index, household size, dwelling, parental education and centre, and for maternal smoking and family history of hayfever and asthma in a subsample (n=2459).

Results
Subjects from Iceland and Norway reported much more frequent intake of fish both in childhood and adulthood as compared with subjects from Sweden, Estonia and Denmark. Current fish intake less than weekly in adults was associated with more asthma symptoms, while more frequent fish intake did not appear to decrease the risk further. No dose–response association was found between childhood fish intake and adult asthma, but those who never ate fish in childhood had an increased risk for asthma and earlier asthma onset. Adult consumption of cod oil had a u‐shaped association with asthma, with the highest risks in those taking cod oil never and daily.

Conclusion
A minimum level of weekly fish intake in adulthood was associated with protection against asthma symptoms in this large North‐European multi‐centre study. Subjects who never ate fish in childhood were at an increased risk for asthma. Both indicate a possible threshold effect of fish on asthma.
Skin prick test can identify eczematous infants at risk of asthma and allergic rhinitis
Authors: Lowe A. J. , Hosking C. S. , Bennett C. M. , Carlin J. B. , Abramson M. J. , Hill D. J. , Dharmage S. C.
Published: October 2007

Background
Assessment of allergic sensitization is not routinely performed in infants and young children with eczema.

Objective
To determine whether infants who have atopic eczema (with sensitization) are at a greater risk of developing asthma and allergic rhinitis (AR) than those with non‐atopic eczema (without concurrent sensitization).

Methods
The presence of eczema was prospectively documented until 2 years of age in a birth cohort of 620 infants with a family history of atopic disease. Sensitization status was determined by skin prick tests (SPTs) at 6, 12, and 24 months using six common allergens. Interviews were conducted at 6 and 7 years to determine the presence of asthma and AR.

Results
Within the first 2 years of life, 28.7% of the 443 children who could be classified had atopic eczema: 20.5% had non‐atopic eczema, 19.0% were asymptomatic but sensitized and 31.8% were asymptomatic and not sensitized. When compared with children with non‐atopic eczema in the first 2 years of life, children with atopic eczema had a substantially greater risk of asthma [odds ratio (OR)=3.52, 95% confidence interval=1.88–6.59] and AR (OR=2.91, 1.48–5.71). The increased risk of asthma was even greater if the infant had a large SPT (OR=4.61, 2.34–9.09) indicative of food allergy. There was no strong evidence that children with non‐atopic eczema had an increased risk of asthma or AR compared with asymptomatic children.

Conclusion
In children with eczema within the first 2 years of life, SPT can provide valuable information on the risk of childhood asthma and AR.
Residential outdoor air pollution and allergen sensitization in schoolchildren in Oslo, Norway
Authors: Oftedal B. , Brunekreef B. , Nystad W. , Nafstad P.
Published: October 2007

Background
Epidemiological studies that have investigated the association between air pollution and atopy have found inconsistent results. Furthermore, often exposure to outdoor air pollution has had limited quality, and more individual exposure is needed.

Objective
To investigate the relations between early and lifetime exposure to residential outdoor air pollution and allergen sensitization in 9–10‐year‐old children in Oslo, Norway.

Methods
Sensitization to common allergens was measured by skin prick tests (SPTs), which were performed in 2244 children who had lived in Oslo since birth. Several definitions of positive SPT were used. Information on potential confounding variables was collected by a parental questionnaire. Exposure to outdoor air pollution was assessed by the EPISODE dispersion model, which calculates hourly concentrations of nitrogen dioxide (NO2), particulate matter (PM) with aerodynamic diameter <10 μm (PM10) and <2.5 μm (PM2.5), respectively.

Results
We found no associations between long‐term air pollution exposure and sensitization to any allergen, any indoor or any pollen allergen. However, lifetime air pollution exposure was associated with sensitization to the house dust mite Dermatophagoides farinae. One interquartile increase of lifetime exposure to NO2, PM10 and PM2.5 was associated with 1.88 (adjusted odds ratio) (1.02, 3.47) [95% confidence interval (CI)], 1.61 (0.96, 2.72) and 1.46 (0.96, 2.22), respectively, for D. farinae. Lifetime exposure was also associated with sensitization to cat in a subpopulation. Both associations diminished after adjusting for a contextual socio‐economic factor.

Conclusion
Long‐term exposure to traffic‐related pollutants was generally not associated with allergen sensitization in 9–10‐year‐old Oslo children. However, lifetime exposure was associated with sensitization to D. farinae, and with sensitization to cat in a subpopulation, which may be explained by socio‐economic confounding or multiple comparisons. The air pollution levels in Oslo may be too low to reveal associations with sensitization.
Increased release of histamine in patients with respiratory symptoms related to perfume
Authors: Elberling J. , Skov P. S. , Mosbech H. , Holst H. , Dirksen A. , Johansen J. D.
Published: October 2007

Background
Environmental perfume exposure may cause respiratory symptoms. Individuals with asthma and perfume contact allergy report such symptoms more frequently than others. However, immunologic mechanisms have not been demonstrated and the symptoms are not associated with IgE‐mediated allergy. The study aimed to investigate whether basophils from patients with respiratory symptoms related to perfume released more histamine in the presence of perfume as compared with healthy volunteers.

Methods
Histamine release was measured by the glass fibre method. Blood was obtained from healthy volunteers (n=20) and patients with respiratory symptoms related to perfume (n=17) attending a dermatological outpatient clinic for patch testing. The effect of an international brand perfume was investigated using the basophil histamine release test with perfume. Furthermore, basophils from a healthy non‐atopic donor were incubated with participant's sera and histamine release induced by perfume was measured.

Results
In both groups incremental perfume concentrations showed a positive and significant (P<0.001) dose‐response effect on the release of histamine. At the highest perfume concentration, the basophils released significantly (P<0.05) more histamine in patients as compared with healthy volunteers. No difference was found between the groups when sera were incubated with basophils from a healthy non‐atopic donor.

Conclusion
Perfume induces a dose‐dependent non‐IgE‐mediated release of histamine from human peripheral blood basophils. Increased basophil reactivity to perfume was found in patients with respiratory symptoms related to perfume.
Human γδ T cells modulate the mite allergen‐specific T‐helper type 2‐skewed immunity
Authors: Korematsu S. , Tanaka Y. , Nagakura T. , Minato N. , Izumi T.
Published: October 2007

Background
γδ T cells have been described as one of immune regulators in patients with infection, malignancy, and allergy.

Objective
To elucidate the ability of γδ T cells as an allergen immunotherapy candidate, the effectiveness of human γδ T cells in allergen‐specific T‐helper type 2 (Th2)‐type T cells was evaluated in vitro.

Methods
House dust mite‐specific Th2‐type T cell clones, Bacillus Calmette–Guerin (BCG)‐specific Th1‐type T cell clones, and γδ T cell lines were established from the peripheral blood mononuclear cells of two patients with allergic rhinitis. The effectiveness of γδ T cells and BCG‐specific Th1‐type T cell clones in the modulation of allergen‐specific Th2 cells in terms of their cytokine productions was evaluated.

Results
In response to cognate antigens, the γδ T cell lines demonstrated a proliferation and production of IFN‐γ that exceeded that of BCG‐specific Th1‐type T cell clones (mean stimulation index: 14.5 vs. 2.8, mean IFN‐γ: 130.5 vs. 10.0 pg/mL). When the γδ T cell lines and mite‐allergen‐specific Th2 clones were co‐cultured with each other, only the levels of IL‐4 (mean, −87%) decreased, but not the levels of IL‐5 and IL‐13, with an increasing concentration of γδ T cell antigen and IFN‐γ production (mean, +730%).

Conclusion
These results demonstrated that γδ T cells derived from allergic patients might thus have a partial ability to modulate allergen‐specific Th2‐skewed immunity.
Fibrin formation by wounded bronchial epithelial cell layers in vitro is essential for normal epithelial repair and independent of plasma proteins
Authors: Perrio M. J. , Ewen D. , Trevethick M. A. , Salmon G. P. , Shute J. K.
Published: October 2007

Background
The bronchial epithelium is in contact with, and continually damaged by, the environment. Animal models have indicated that normal epithelial repair is rapid and supported by the formation of a provisional fibrin matrix that is exclusively plasma‐derived.

Objectives
Our objectives were to demonstrate the ability of normal human bronchial epithelial (NHBE) cells to produce coagulation cascade proteins and form fibrin in response to damage, independently of plasma proteins, and to show that formation of a cross‐linked fibrin matrix is essential for normal epithelial repair in vitro.

Methods
Primary NHBE cells and cells of the 16HBE 14o‐ bronchial epithelial cell line were grown and maintained in vitro prior to mechanical wounding of confluent monolayers in serum‐free media. Tissue factor (TF) and factor XIII (FXIII) were visualized on 16HBE 14o‐ monolayers using immunohistochemistry. The time‐dependent expression of TF, factor VII (FVII), factor X (FX), fibrinogen, soluble fibrin, FXIII subunit A (FXIIIA) and D‐dimers following wounding of confluent 16HBE 14o‐ monolayers was investigated using immunoassays. TF and FVII expression at the mRNA level was investigated by RT‐PCR. The role of coagulation cascade proteins in the repair response of NHBE and 16HBE 14o‐ monolayers was investigated using neutralizing antibodies.

Results
Active TF was constitutively expressed in 16HBE 14o‐ cells. Levels of FVII, FX, fibrinogen, soluble fibrin, FXIIIA and D‐dimers in culture supernatants increased rapidly and were maximal 20 min after wounding the monolayers. Expression of TF and FVII mRNA was significantly increased 10 and 4 h, respectively, after wounding. Neutralizing antibodies to TF, fibrinogen and FXIIIA significantly inhibited repair of NHBE and 16HBE 14o‐ cell layers.

Conclusions
The bronchial epithelium has the potential to respond rapidly to mechanical damage by forming a cross‐linked fibrin matrix that is essential for normal epithelial repair, independently of plasma proteins.
Differential activation of dendritic cells by nerve growth factor and brain‐derived neurotrophic factor
Authors: Noga O. , Peiser M. , Altenähr M. , Knieling H. , Wanner R. , Hanf G. , Grosse R. , Suttorp N.
Published: October 2007

Background
Neurotrophins are involved in inflammatory reactions influencing several cells in health and disease including allergy and asthma. Dendritic cells (DCs) play a major role in the induction of inflammatory processes with an increasing role in allergic diseases as well.

Objective
The aim of this study was to investigate the influence of neurotrophins on DC function.

Methods
Monocyte‐derived dendritic cells were generated from allergic and non‐allergic donors. Neurotrophin receptors were demonstrated by western blotting, flow cytometry and fluorescence microscopy. Activation of small GTPases was evaluated by pull‐down assays. DCs were incubated with nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) and supernatants were collected for measurement of IL‐4, IL‐6, IL‐10, IL‐12p70, TNF‐α and TGF‐β.

Results
Receptor proteins were detectable by western blot, fluorescence activated cell sorting analysis and fluorescence microscopy. Signalling after neurotrophin stimulation occurred in a ligand‐specific pattern. NGF led to decreased RhoA and increased Rac activation, while BDNF affected RhoA and Rac activity in a reciprocal fashion. Cells of allergics released a significantly increased amount of IL‐6, while for healthy subjects a significantly higher amount of IL‐10 was found.

Conclusion
These data indicate that DCs are activated by the neurotrophins NGF and BDNF by different pathways in a receptor‐dependant manner. These cells then may initiate inflammatory responses based on allergic sensitization releasing preferred cytokines inducing tolerance or a T‐helper type 2 response.
A general population from Thailand: incidence of common allergens with emphasis on para‐phenylenediamine
Authors: White J. M. L. , Gilmour N. J. , Jeffries D. , Duangdeeden I. , Kullavanijaya P. , Basketter D. A. , McFadden J. P.
Published: October 2007

Background
Most studies on the prevalence of allergy to the permanent hair dye chemical para‐phenylenediamine (PPD) are reported from populations of eczema patients attending patch‐test clinics, and are assumed to be much higher than in the normal population. No data exist on incidence of senitization to PPD resulting from the use of commercial hair dye preparations over a defined time period.

Method
A total of 2545 healthy adult volunteers (Bangkok) were screened for PPD allergy through standard patch testing. Volunteers not allergic to PPD were then recruited into two groups: one group applying a commercial hair dye brand as instructed on a monthly basis for 6 months (n=548) and the other group (controls) (n=516) was instructed not to dye their hair for 6 months. Sensitization to PPD resulting from the use of hair dye over this period was then detected by repeat patch testing.

Results
The prevalence of PPD allergy in a normal adult population was 2.7% (m=2.4%, f=3.2%). Projected to the adult Thai population, at least 1 000 000 Thai individuals could be allergic to PPD. The incidence of sensitization through the monthly application of standard commercial hair dye preparations over a 6‐month period was 1.3%, substantially higher than in controls (0.4%), although numbers were small and not statistically significant.

Interpretation
There is a higher prevalence of hair dye allergy among the normal population than previously thought. The incidence of new cases of PPD allergy would indicate that current regulations and practice of hair dye exposure lead to PPD sensitization and allergy, which is a public health problem.
Atopic features of cough variant asthma and classic asthma with wheezing
Authors: Takemura M. , Niimi A. , Matsumoto H. , Ueda T. , Yamaguchi M. , Matsuoka H. , Jinnai M. , Chin K. , Mishima M.
Published: October 2007

Background
Cough variant asthma is a phenotype of asthma solely presenting with coughing. It involves airway inflammation and remodelling as does classic asthma with wheezing, and a subset of patients may progress to classic asthma. The atopic features of cough variant asthma remain unclear.

Objective
To compare atopic features between patients with cough variant asthma and those with classic asthma, and to examine the possible correlation of these features with the future development of wheezing in the former group.

Methods
Total and specific IgE levels of seven common aeroallergens [house dust mite (HDM), Gramineae/Japanese cedar/weed pollens, moulds, cat/dog dander] were examined in 74 cough variant asthma patients and in 115 classic asthma patients of varying severity. Forty of the former patients were prospectively observed for 2 years to determine whether cough variant asthma progressed to classic asthma despite inhaled corticosteroid treatment.

Results
Patients with classic asthma had higher total IgE (P<0.0001), larger numbers of sensitized allergens (P=0.03), and higher rates of sensitization to dog dander (24% vs. 3%, P<0.0001), HDM (46% vs. 28%, P=0.02), and moulds (17% vs. 7%, P=0.047) than did patients with cough variant asthma. Wheezing developed in six (15%) patients with cough variant asthma, who were sensitized to larger numbers of allergens (P=0.02) and had higher rates of sensitization to HDM (P=0.01) and dog dander (P=0.02) than the 34 patients in whom wheezing did not develop. Among the patients with classic asthma, total and specific IgE variables were similar in the subgroup with mild disease (n=60) and the subgroup with moderate‐to‐severe disease (n=55), as reported previously.

Conclusions
Atopy may be related to the development of wheezing in patients with cough variant asthma. To prevent the progression of cough variant asthma to classic asthma, avoidance of relevant allergens may be essential.