bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional autoregulation by quorum sensing Escherichia coli regulators B and C (QseBC) in enterohaemorrhagic E. coli (EHEC)
Authors: Clarke Marcie B. , Sperandio Vanessa
Published: August 2005

The cell‐to‐cell communication system referred to as quorum sensing (QS) is based on the principle that bacteria secrete hormone‐like compounds referred to as autoinducers. Upon reaching a threshold concentration, these autoinducers interact with transcription factors to regulate gene expression. We previously reported that enterohaemorrhagic Escherichia coli (EHEC), which is responsible for outbreaks of bloody diarrhoea, utilizes a QS system to regulate gene transcription. We have also previously shown that the quorum sensing E. coli regulators B and C (QseBC) may act as a two‐component system to transcriptionally regulate the expression of flagella and motility. Here, using a reverse transcription polymerase chain reaction (RT‐PCR), we show that qseBC are transcribed in an operon. Furthermore, using a qseBC::lacZ transcriptional fusion, we observed that QseB autoactivates its own transcription. In addition, the transcriptional start site of the qseBC promoter responsive to QseBC was mapped, and single‐copy and multicopy deletion analyses were performed to determine the minimal region necessary for QseB transcriptional activation. These data allowed us to map an additional transcriptional start site for the qseBC promoter which may allow for a basal level of QseBC expression. Finally, electrophoretic mobility shift assays, competition experiments and DNase I footprints were performed and demonstrated that QseB directly binds to two sites in its own promoter. These results indicate that QseB may act to autoregulate its own transcription through binding to low‐ and high‐affinity sites found in its promoter.
Effect of tegaserod on gut transit in male and female subjects
Authors: Degen L. , Petrig C. , Studer D. , Schroller S. , Beglinger C.
Published: September 2005

Abstract  Tegaserod is a novel selective serotonin receptor type‐4 (5‐HT4) partial agonist that stimulates gastrointestinal (GI) motility. Tegaserod has proven efficacy in irritable bowel syndrome with constipation in women and in men and women with chronic idiopathic constipation. The effects on gastric emptying, small bowel transit and colonic transit have not been studied in detail in male and female subjects. This study aimed therefore to assess the effect of gender on GI transit with and without tegaserod. A randomized, placebo‐controlled, double‐blind, crossover study was performed in 40 healthy subjects (23 males, 17 females). Each treatment period involved three and a half days of bid treatment with either 6 mg tegaserod or an identical placebo. Transit parameters were assessed by a scintigraphy. Tegaserod significantly accelerated gastric emptying, small bowel and colonic transit times (P < 0.05–0.0001). The effect was more apparent in male subjects than in females (P = 0.044 to P < 0.0001). The most striking prokinetic effects were observed in the upper GI tract (stomach and small intestine). In both healthy male and female subjects, tegaserod markedly accelerated small intestinal transit, and induced a significant increase in gastric emptying time and colonic transit. The results imply that tegaserod is a potent prokinetic agent throughout the GI in both sexes.
Priming of the immune response by schistosome eggs
Authors: PEARCE E. J.
Published: August 2005

Schistosomiasis mansoni is a chronic disease caused by infection with helminths of the genus Schistosoma mansoni. Adult schistosomes live intravascularly, and for transmission of this infection it is necessary for parasite eggs to traverse the endothelium, and migrate to the intestinal lumen, from where they can exit the body to continue the lifecycle. This process is dependent on an intact host CD4 T helper (Th) cell response to egg antigens. Perhaps because of this, eggs have evolved to be highly immunogenic and capable of inducing potent Th responses. The egg‐induced Th response is unusual in that it is highly Th2‐polarized. The selective pressure on the host to mount a Th2 response against eggs is apparent in the fact that Th2 response‐defective mice develop acutely lethal disease when infected with schistosomes. In this review I will focus on the underlying basis for the Th2 bias in the immune response to egg antigens.
Immunity to schistosomiasis in animals: an update
Authors: VERCRUYSSE J. , GABRIEL S.
Published: August 2005

The present paper reviews the available literature on the development of immunity to animal Schistosoma infections. The majority of the studies on animal schistosomiasis were performed in cattle and pigs and only Schistosoma mattheei, S. bovis and S. japonicum received particular attention, mainly because of their recognized veterinary significance or zoonotic aspect. Although it is an accepted fact that acquired resistance to Schistosoma is of major importance in the regulation of infection intensity in the field, almost nothing is yet known of either the nature of the antigens or of the immune mechanisms involved. The recent studies on immunity development focus in particular on the occurrence of maternal to foetal transfer of immunological substances related to animal Schistosoma infections and possible effects of these transfers on the immunity development of the foetus/newborn. Since congenital infections for Schistosoma species other than S. japonicum are extremely rare, the most plausible route for foetal contact is the transplacental or postnatal transfer of immunological substances. Prenatal transfers of specific antibodies and antigens via placental lesions and postnatal transfers via the colostrum were observed in cattle and pigs, and subsequent modifications of the immune response of the newborn were observed. Placental lesions induced by Schistosoma eggs could allow other pathogens to cross the placenta.
Schistosome glycans and innate immunity
Authors: HOKKE C. H. , YAZDANBAKHSH M.
Published: August 2005

Schistosome glycans induce characteristic innate immune responses in the infected host. The molecular aspects of these responses, the pathways and receptors as well as the schistosome glycans and glycoconjugates involved, form an area of intense research. The relevant schistosome glycan elements and the possible mechanisms through which they act on the innate immune system are discussed in this review.
Resistance to re‐infection after exposure to normal and attenuated schistosome parasites in the baboon model
Authors: KARIUKI T. M. , FARAH I. O.
Published: August 2005

The baboon model of schistosomiasis has been used extensively to study parasite biology, immune responses and pathological manifestations after natural and experimental infections. The body of knowledge accumulated so far has placed this animal model at the pinnacle in the continuing search for new interventions and might hold the key to the development of new anti‐schistosome vaccines. In this review paper, we highlight previous and recent studies that have elevated the baboon to be the model of choice for schistosomiasis research. In particular, the long‐term studies of re‐infection after chemotherapy as well as the interaction between vaccination, chemotherapy and infection are highlighted.
Participation of Xanthomonas axonopodis pv. citri hrp cluster in citrus canker and nonhost plant responses
Authors: Dunger G. , Arabolaza A. L. , Gottig N. , Orellano E. G. , Ottado J.
Published: September 2005

The participation of the Xanthomonas axonopodis pv. citri hypersensitive response and pathogenicity (hrp) cluster in interactions with host and nonhost plants was characterized in pathogenicity and avirulence models. The hrp cluster encodes the type III secretion system indispensable for trafficking of proteins to the plant cell. Mutations in operons hrpB and hrpD and the hrpF gene failed to produce canker in citrus plants or hypersensitive response in cotton plants. The interaction of the phytopathogen with various nonhost plants has been characterized. The results showed that the hypersensitive response is activated in leaves of cotton, bean, tobacco, tomato, pepper and Nicotiana benthamiana, and that genes present in operons hrpB and hrpD and the hrpF gene are required for pathogenicity in hosts and induction of the hypersensitive response in nonhost plants.
Origins, genetic organization and transcription of a family of non‐autonomous helitron elements in maize
Authors: Brunner Stephan , Pea Giorgio , Rafalski Antoni
Published: September 2005

Helitron transposable elements carrying gene fragments were recently discovered in maize. These elements are frequently specific to certain maize lineages. Here we report evidence supporting the involvement of helitrons in the rapid evolution of the maize genome, in particular in the multiplication of related genic fragments across the genome. We describe a family of four closely related, non‐autonomous maize helitrons and their insertion sites at four non‐allelic genetic loci across the maize genome: two specific to the B73 inbred, and two to the Mo17 inbred. We propose the phylogeny of this helitron family and provide an approximate timeline of their genomic insertions. One of these elements, the Mo17‐specific helitron on chromosome 1 (bin 1.07), is transcriptionally active, probably as a result of insertion in the vicinity of a promoter. Significantly, it produces an alternatively spliced and chimeric transcript joining together genic segments of different chromosomal origin contained within the helitron. This transcript potentially encodes up to four open reading frames. During the course of evolution, transcribed helitrons containing multiple gene fragments may occasionally give rise to new genes with novel biochemical functions by a combinatorial assembly of exons. Thus helitrons not only constantly reshape the genomic organization of maize and profoundly affect its genetic diversity, but also may be involved in the evolution of gene function.
Arabidopsis RecQl4A suppresses homologous recombination and modulates DNA damage responses
Authors: Bagherieh‐Najjar Mohammad B. , de Vries Onno M.H. , Hille Jacques , Dijkwel Paul P.
Published: September 2005

The DNA damage response and DNA recombination are two interrelated mechanisms involved in maintaining the integrity of the genome, but in plants they are poorly understood. RecQ is a family of genes with conserved roles in the regulation of DNA recombination in eukaryotes; there are seven members in Arabidopsis. Here we report on the functional analysis of the Arabidopsis RecQl4A gene. Ectopic expression of Arabidopsis RecQl4A in yeast RecQ‐deficient cells suppressed their hypersensitivity to the DNA‐damaging drug methyl methanesulfonate (MMS) and enhanced their rate of homologous recombination (HR). Analysis of three recQl4A mutant alleles revealed no obvious developmental defects or telomere deregulation in plants grown under standard growth conditions. Compared with wild‐type Arabidopsis, the recQl4A mutant seedlings were found to be hypersensitive to UV light and MMS, and more resistant to mitomycin C. The average frequency of intrachromosomal HR in recQl4A mutant plants was increased 7.5‐fold over that observed in wild‐type plants. The data reveal roles for Arabidopsis RecQl4A in maintenance of genome stability by modulation of the DNA damage response and suppression of HR.
Arabidopsis peroxisomes possess functionally redundant membrane and matrix isoforms of monodehydroascorbate reductase
Authors: Lisenbee Cayle S. , Lingard Matthew J. , Trelease Richard N.
Published: September 2005

The H2O2 byproduct of fatty acid catabolism in plant peroxisomes is removed in part by a membrane‐associated antioxidant system that involves both an ascorbate peroxidase and a monodehydroascorbate reductase (MDAR). Despite descriptions of 32‐kDa MDAR polypeptides in pea and castor peroxisomal membranes and cDNA sequences for several ‘cytosolic’ MDARs, the genetic and protein factors responsible for peroxisomal MDAR function have yet to be elucidated. Of the six MDAR polypeptides in the Arabidopsis proteome, named AtMDAR1 to AtMDAR6 in this study, 47‐kDa AtMDAR1 and 54‐kDa AtMDAR4 possess amino acid sequences that resemble matrix (PTS1) and membrane peroxisomal targeting signals, respectively. Epitope‐tagged versions of these two MDARs and a pea 47‐kDa MDAR (PsMDAR) sorted in vivo directly from the cytosol to peroxisomes in Arabidopsis and BY‐2 suspension cells, whereas AtMDAR2 and AtMDAR3 accumulated in the cytosol. The PTS1‐dependent sorting of AtMDAR1 and PsMDAR to peroxisomes was incomplete (inefficient?), but was improved for PsMDAR after changing its PTS1 sequence from –SKI to the canonical tripeptide –SKL. A C‐terminal transmembrane domain and basic cluster of AtMDAR4 were necessary and sufficient for targeting directly to peroxisomes. MDAR activity in isolated Arabidopsis peroxisomes was distributed among both water‐soluble matrix and KCl‐insoluble membrane subfractions that contained respectively 47‐ and 54‐kDa MDAR polypeptides. Notably, a 32‐kDa MDAR was not identified. Combined with membrane association and topological orientation findings, these results indicate that ascorbate recycling in Arabidopsis (and probably other plant) peroxisomes is coordinated through functionally redundant MDARs that reside in the membrane and the matrix of the organelle.
A community‐based study to examine the effect of a youth HIV prevention intervention on young people aged 15–24 in South Africa: results of the baseline survey
Authors: Pettifor Audrey E. , Kleinschmidt Immo , Levin Jonathan , Rees Helen V. , MacPhail Catherine , Madikizela‐Hlongwa Lindiwe , Vermaak Kerry , Napier Grant , Stevens Wendy , Padian Nancy S.
Published: August 2005

Objectives  To determine whether South African youths living in communities that had either of two youth human immunodeficiency virus (HIV) prevention interventions [(a) loveLife Youth Centre or (b) loveLife National Adolescent Friendly Clinic Initiative] would have a lower prevalence of HIV, sexually transmitted infections (STIs), and high risk sexual behaviours than communities without either of these interventions.

Methods  In 2002 the baseline survey of a quasi‐experimental, community‐based study was conducted in South Africa. In total 33 communities were included in three study arms (11 communities per study arm). The final sample included 8735 youths aged 15–24 years. All participants took part in a behavioural interview and were tested for HIV, gonorrhoea (Neisseria gonorrhoeae) and Chlamydia (Chlamydia trachomatis).

Results  HIV prevalence was 20.0% among females and 7.5% among males (OR 3.93 95% CI 2.51–6.15). There were no significant differences between study arms for HIV, NG or CT prevalence at baseline. In multiple regression analyses, HIV was significantly associated with NG infection (OR 1.96 95% CI 1.24–3.12) but not with CT infection. Youths who reported >1 lifetime partner were also significantly more likely to be infected with HIV (OR 1.98 95% CI 1.55–2.52), as were those who reported ever having engaged in transactional sex (OR 1.86 P = 0.02) or having had genital ulcers in the past 12 months (OR 1.71 P ≤ 0.001).

Conclusions  HIV prevention programmes must ensure that gender inequities that place young women at greater risk for HIV infection are urgently addressed and they must continue to emphasize the importance of reducing the number of sexual partners and STI treatment.
Birth month and sensitization to house dust mites in asthmatic children
Authors: Yoo Y. , Yu J. , Kang H. , Kim D. K. , Koh Y. Y. , Kim C. K.
Published: August 2005

Background:  Early exposure to high quantities of allergen has an important role in the incidence of atopic sensitization. In fact, subjects sensitized to house dust mites (HDMs) have a significantly higher proportion of births in the season when HDMs are most abundant.

Objective:  The aim of this study was to investigate whether birth month patterns differ for asthmatic patients sensitized only to HDMs and for those sensitized to HDMs and other allergen(s).

Methods:  Among 2225 patients with asthma, aged 10–16 years, 1642 sensitized to HDMs were identified by skin prick testing. This group was composed of patients sensitized only to HDMs (n = 715) and patients sensitized to HDMs and other allergen(s) (n = 927). The birth month distributions of the group of HDM‐sensitive asthmatics or its subgroups were compared with that of a reference population (total live births in the same years as the studied subjects). The risk ratio of a given birth month in relation to all the other months was calculated as an odds ratio (OR) with the corresponding 95% confidence interval (CI).

Results:  A significant difference in birth month distribution was observed for HDM‐sensitive asthmatics (χ2 = 23.6, P = 0.015), with higher rates of birth in August (OR: 1.23, 95% CI: 1.04–1.46) and September (1.24, 1.04–1.46). When the two subgroups were analyzed separately, significantly more births were noted in August (1.34, 1.06–1.71) and September (1.34, 1.05–1.70) for those sensitized only to HDMs, whereas no such birth month preference was observed for those sensitized to HDMs and other allergen(s).

Conclusions:  The HDM‐positive asthmatics showed a greater proportion of births in August and September, which correspond to high HDM exposure. However, this birth month pattern was evident in asthmatic‐sensitive only to HDMs, but was not observed in those sensitive to HDMs and other allergen(s).
Detection of differentiation‐ and activation‐linked cell surface antigens on cultured mast cell progenitors
Authors: Schernthaner G.‐H. , Hauswirth A. W. , Baghestanian M. , Agis H. , Ghannadan M. , Worda C. , Krauth M.‐T. , Printz D. , Fritsch G. , Sperr W. R. , Valent P.
Published: August 2005

Background:  Mast cells (MC) are multifunctional effector cells of the immune system. They derive from uncommitted CD34+ hemopoietic progenitor cells (HPC). Depending on the stage of maturation and the environment, MC variably express differentiation‐ and activation‐linked antigens. Little is known, however, about the regulation of expression of such antigens in immature human MC.

Methods:  We analyzed expression of CD antigens on human MC grown from cord blood‐derived CD34+ HPC. The HPC were isolated by magnetic cell sorting (MACS) and FACS to >97% purity, and were cultured in stem cell factor (SCF) and interleukin (IL)‐6 with or without additional cytokines (IL‐4 or IL‐10) in serum‐free medium. The cell surface phenotype of MC was determined by monoclonal antibodies and flow cytometry.

Results:  Cultured MC progenitors were found to react with antibodies against various CD antigens including CD58, CD63, CD117, CD147, CD151, CD203c, and CD172a, independent of the growth factors used and time‐point investigated (days 14–42). CD116 [granulocyte–macrophage colony‐stimulating factor receptor α (GM‐CSFRα)] and CD123 (IL‐3Rα) were expressed on MC precursors on day 14, but disappeared thereafter. Cultured MC did not express CD2, CD3, CD5, CD10, CD19, or CD25. Addition of IL‐10 to MC cultures showed no effect on expression of CD antigens. However, IL‐4 was found to promote expression of CD35 and CD88 on cultured MC without changing expression of other CD antigens.

Conclusions:  Most MC antigens may already be expressed at an early stage of mastopoiesis. Whereas IL‐3R and GM‐CSFRs are lost during differentiation of MC, these cells may acquire complement receptors (CD35, CD88) under the influence of distinct cytokines.
The potential of proteomics and peptidomics for allergy and asthma research
Authors: Crameri R.
Published: August 2005

Progress in the field of proteomics, the branch of biology that studies the full set of proteins derived from a given genome, is moving fast. Two‐dimensional gel electrophoresis (2DG) separation of complex protein mixtures and the subsequent analysis of isolated protein spots by mass spectrometry allow fast and accurate identification of proteins. The comparison of spots from different samples separated on customized 2D gels allows the detection of punctual differences in their mobility and facilitates tracing back differences in protein expression, presence of isoforms, splice variants and posttranslational modifications by mass spectrometry. In spite of significant analytical challenges owing to the high complexity of the proteome and the challenge deriving from the necessity to process huge amounts of raw data generated by mass spectrometric profiling, proteomics has evolved to an indispensable tool in life sciences. A restricted window of the proteome that consists of peptides and small proteins not easily manageable by conventional gel electrophoresis prompted the development of separation methods based on liquid chromatography. This new research field termed peptidomics already contributed, together with proteomics to enlarge our knowledge about biological processes and supported by sophisticated bioinformatics tools, to the discovery of new diagnostic and therapeutic targets. The technological capabilities of biophysical separation, mass spectrometry and bioinformatics form the basis of discovery programs that aim at mining the proteome starting from microgram amounts of protein extracts derived from body fluids and tissues. Proteomics and peptidomics have a great potential to speed up allergy and asthma research, where disease‐ and tissue‐specific samples are easy to obtain.
The effect of thermal processing on the IgE reactivity of the non‐specific lipid transfer protein from apple, Mal d 3
Authors: Sancho A. I. , Rigby N. M. , Zuidmeer L. , Asero R. , Mistrello G. , Amato S. , González‐Mancebo E. , Fernández‐Rivas M. , van Ree R. , Mills E. N. C.
Published: August 2005

Background:  Non‐specific lipid transfer proteins (LTPs) are involved in allergy to fresh and processed fruits. We have investigated the effect of thermal treatment and glycation on the physico‐chemical and IgE‐binding properties of the LTP from apple (Mal d 3).

Methods:  Mal d 3 was purified from apple peel and the effect of heating in the absence and presence of glucose investigated by CD spectroscopy, electrospray and MALDI‐TOF mass spectrometry. IgE reactivity was determined by RAST and immunoblot inhibition, SPT and basophil histamine release test.

Results:  The identity and IgE reactivity of purified Mal d 3 was confirmed. Mild heat treatment (90°C, 20 min) in the absence or presence of glucose did not alter its IgE reactivity. More severe heat treatment (100°C, 2 h) induced minor changes in protein structure, but a significant decrease in IgE‐binding (30‐fold) and biological activity (100‐ to 1000‐fold). Addition of glucose resulted in up to four glucose residues attached to Mal d 3 and only a 2‐ and 10‐fold decrease of IgE‐binding and biological activity, respectively.

Conclusions:  Only severe heat treatment caused a significant decrease in the allergenicity of Mal d 3 but glycation had a protective effect. The presence of sugars in fruits may contribute to the thermostability of the allergenic activity of LTP in heat‐processed foods.
Association study of mast cell chymase polymorphisms with atopy
Authors: Weidinger S. , Rümmler L. , Klopp N. , Wagenpfeil S. , Baurecht H. J. , Fischer G. , Holle R. , Gauger A. , Schäfer T. , Jakob T. , Ollert M. , Behrendt H. , Wichmann H. E. , Ring J. , Illig T.
Published: August 2005

Background:  Atopic disorders are the result of complex interactions between genetic and environmental factors. Associations analyses between the promoter polymorphism rs1800875 in the mast cell chymase gene (CMA1) and atopy‐related phenotypes have yielded inconsistent results.

Methods:  We sequenced the CMA1 locus in 24 unrelated healthy individuals with serum IgE levels <50% percentile and 24 individuals with atopic eczema and serum IgE levels >90% percentile. Seven CMA1 single nucleotide polymorphisms (SNPs) were evaluated for evidence of associations with atopic phenotypes within a large population of German adults (n = 1875). Subjects were phenotyped by standardized questionnaires and interviews, skin prick testing and serum IgE measurements. Genotyping was performed using MALDI‐TOF MS (Matrix‐Assisted Laser Desorption Ionization–Time of Flight mass spectrometry).

Results:  Promoter polymorphism rs1800875 was significantly associated with atopic eczema. No associations between any other single SNP and atopic phenotypes could be detected. Haplotype reconstruction revealed four of 128 possible haplotypes reaching estimated frequencies of 3% or more. Two of these haplotypes showed a borderline‐significant association with atopic eczema, which did not remain significant after correction for multiple testing.

Conclusions:  Results confirm previous observations of a significant association between the CMA1 promoter polymorphism rs1800875 and atopic eczema, but not with serum IgE levels, and support the hypothesis that CMA1 serves as candidate gene for atopic eczema.
Human mast cells release Interleukin‐8 and induce neutrophil chemotaxis on contact with activated T cells
Authors: Salamon P. , Shoham N. G. , Gavrieli R. , Wolach B. , Mekori Y. A.
Published: August 2005

Background:  Mast cells have recently been shown to control neutrophil recruitment during T‐cell mediated cutaneous DTH reaction in vivo through TNF‐α and MIP‐2, the functional murine analogue of human IL‐8. Although the nature of signals transmitted from T cells which activate mast cells has not yet been defined, we hypothesized that a direct cross‐talk (i.e. heterotypic adhesion) between these two cell populations exists, as has previously been reported.

Aims:  The present study was aimed at gaining insight into the functional role of mast cell–T cell contact in expression and release of IL‐8, and its effect on neutrophil chemotaxis.

Methods:  The IL‐8 gene expression was identified by Affymetrix GeneChip arrays, validated by RT‐PCR and the protein measured by ELISA. Chemotaxis was evaluated by using a modified Boyden chamber assay.

Results:  Mast cells were found to express and release significantly higher concentrations of IL‐8 on incubation with membranes obtained from activated, as compared to resting T cells. Supernatants obtained from these activated mast cells induced significant neutrophil chemotaxis that was inhibited by neutralizing mAb to IL‐8.

Conclusions:  Thus, activated T cells, on heterotypic adhesion to mast cells, deliver the necessary signals for the latter to release cytokines and chemokines necessary for cell migration to sites of antigen challenge, thereby facilitating T‐cell mediated inflammatory processes.
In vivo relationship between collagenase‐2 and interleukin‐8 but not tumour necrosis factor‐α in chronic rhinosinusitis with nasal polyposis
Authors: Kostamo K. , Sorsa T. , Leino M. , Tervahartiala T. , Alenius H. , Richardson M. , Toskala E.
Published: August 2005

Background:  The characteristic feature of chronic rhinosinusitis with nasal polyposis (CRSwNP) is eosinophilic inflammation of the sinus mucosa; a type of inflammation also seen in asthmatic airways. Similar histopathologic findings of airway remodelling are present in both diseases. Remodelling is tightly controlled by matrix metalloproteinases (MMP). Increase of collagenase‐2 (MMP‐8) expression in the bronchial epithelial cells has been described in asthmatic patients, but it has not been studied in CRSwNP.

Methods:  The concentrations and degree of activation of MMP‐8 were analysed by immunofluorometric assay and Western blotting, respectively, in sinus mucus samples from CRSwNP patients and in nasal lavages from healthy controls in relation to inductive cytokines interleukin‐8 (IL‐8) and tumour necrosis factor‐α (TNF‐α).

Results:  Significantly elevated levels of MMP‐8 and IL‐8 but not TNF‐α were found in CRSwNP patients relative to controls. In particular, the activation of mesenchymal‐type MMP‐8 but not polymorphonuclear‐type MMP‐8 was associated with elevated IL‐8 levels.

Conclusions:  The IL‐8 and MMP‐8 seemingly form an inductive cytokine‐proteinase cascade in CRSwNP pathogenesis. Together they provide a target for novel therapies and a diagnostic tool for monitoring CRSwNP treatment.
Defining childhood atopic phenotypes to investigate the association of atopic sensitization with allergic disease
Authors: Kurukulaaratchy R. J. , Matthews S. , Arshad S. H.
Published: August 2005

Aims: Although atopic sensitization is common in childhood, its relationship to clinical allergic disease remains incompletely understood. We therefore sought to explore this relationship by defining sensitization based atopic phenotypes.

Methods: Children were recruited at birth (n = 1456) and reviewed at 1, 2, 4 and 10 years. Skin prick testing (SPT) to common allergens was done at 4 (n = 980) and 10 years (n = 1036) with lung function (n = 981), bronchial challenge (n = 784) and serum IgE (n = 953) testing at 10. Atopic phenotypes were defined, by sensitization pattern, for children with SPT at both 4 and 10 years (n = 823).

Results: Of phenotyped children, 68.0% were never atopic, 4.3% early childhood atopic (only atopic at age 4), 16.5% chronic childhood atopics (at 4 and 10 years) and 11.2% delayed childhood atopics (only at 10). Never atopics showed small but identifiable prevalence of allergic diseases such as asthma, eczema and rhinitis. Amongst allergen‐sensitized subjects, aeroallergen predominated over food sensitization throughout childhood. Chronic childhood atopics showed highest prevalence of lifetime plus persistent wheeze, eczema and rhinitis, increased prevalence of aeroallergen sensitization, some evidence of persistent food sensitization, significantly greater cord IgE than never atopics (P = 0.006), plus higher total IgE (P < 0.001) and bronchial hyper‐responsiveness (P < 0.001) at 10 years than other phenotypes.

Conclusion: A proportion of childhood eczema, rhinitis and asthma is nonatopic. The commonest childhood pattern of atopy is chronic sensitization, associated with early, persisting and clinically significant allergic disease. The currently accepted childhood ‘Allergic March’ may oversimplify the natural history of childhood atopy and allergic disease.
Standard skin prick testing and sensitization to inhalant allergens across Europe – a survey from the GA2LEN network*
Authors: Heinzerling L. , Frew A. J. , Bindslev‐Jensen C. , Bonini S. , Bousquet J. , Bresciani M. , Carlsen K.‐H. , van Cauwenberge P. , Darsow U. , Fokkens W. J. , Haahtela T. , van Hoecke H. , Jessberger B. , Kowalski M. L. , Kopp T. , Lahoz C. N. , Lodrup Carlsen K. C. , Papadopoulos N. G. , Ring J. , Schmid‐Grendelmeier P. , Vignola A. M. , Wöhrl S. , Zuberbier T.
Published: August 2005

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA2LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA2LEN Pan‐European core SPT panel.
Mast cell myositis: a new feature of allergic asthma?
Authors: Berger P. , Girodet P.‐O. , Manuel Tunon‐de‐Lara J.
Published: August 2005

There is some evidence that, in asthma, mast cells infiltrate the airway smooth muscle layer and, as a consequence, alter the functional and structural properties of myocytes. This inflammation so‐called mast‐cell myositis, probably contributes to both bronchial hyperresponsiveness and airway remodelling. Previous observations have pointed out the presence of mast cells within airway smooth muscle of atopic patients and recent data obtained in asthmatic patients demonstrate that this infiltration is more important in asthmatic patients with atopy. Although the mechanism of such a mast cell attraction remains to be fully understood, experimental data demonstrate that, upon stimulation by tryptase or cytokines, smooth muscle cells can attract mast cells through the production of TGF‐β1 or SCF. Once at the site of inflammation, activated mast cells are responsible for an important extracellular deposition of inflammatory products that may facilitate the increase in smooth muscle mass. In addition, comparison of asthmatic patients with and without atopy suggests that mast cell myositis is closely related with atopy.
The future of microarray technology: networking the genome search
Authors: D'Ambrosio C. , Gatta L. , Bonini S.
Published: August 2005

In recent years microarray technology has been increasingly used in both basic and clinical research, providing substantial information for a better understanding of genome‐environment interactions responsible for diseases, as well as for their diagnosis and treatment. However, in genomic research using microarray technology there are several unresolved issues, including scientific, ethical and legal issues. Networks of excellence like GA2LEN may represent the best approach for teaching, cost reduction, data repositories, and functional studies implementation.
Asthma in medium altitude – exercise‐induced bronchoconstriction in hypobaric environment in subjects with asthma
Authors: Berntsen S. , Stensrud T. , Ingjer F. , Vilberg A. , Carlsen K.‐H.
Published: August 2005

Background:  Hypoxic gas inhalation has been reported to enhance airway responsiveness and results in bronchoconstriction in animal models and in humans with asthma. However, the data have so far been conflicting. The aim of the present study was to examine the effect of reduced barometric pressure on exercise‐induced bronchoconstriction (EIB) in subjects with asthma.

Methods:  Twenty subjects (10–45 years old, ♂/♀ = 13/7) with asthma (at least 10% reduction in forced expiratory volume in 1‐second postexercise) participated in exercise testing in barometric pressure corresponding to altitudes of 200 (normobaric) and 2500 (hypobaric) m above sea level in random order on separate days. Lung function was measured before and after exercise, as well as after inhalation of salbutamol. Heart rate, oxygen uptake (), arterial oxygen saturation (SpO2), respiratory gas exchange ratio (RER) and minute ventilation () were measured during exercise.

Results:  There was no difference in lung function after exercise. The and HRpeak during exercise did not differ. The RERpeak was higher (P = 0.04) in hypobaric environment. The decreased 10.1% (7.2–13.0) [mean (95% confidence intervals)] (P < 0.001) from normobaric to hypobaric environment. At the same time, SpO2 at decreased from 94.4 (92.2–96.6) to 85.6% (82.8–88.4) (P < 0.001).

Conclusions:  A barometric pressure corresponding to altitude of 2500 m did not increase EIB in subjects with asthma. The reduction in is most probably due to the lower SpO2 in hypobaric environment.
Discrepancies in upper and lower limb patterning in split hand foot malformation
Authors: Elliott AM , Reed MH , Roscioli T , Evans JA
Published: August 2005

Split hand foot malformation (SHFM) is genetically heterogeneous with five loci mapped to date. Highly variable in presentation, it can occur as an isolated finding or with other anomalies. The genetic heterogeneity and clinical variability make genetic counselling of SHFM families challenging. By establishing genotype/phenotype correlations, one can provide insight into responsible developmental genes and help to direct mapping efforts and target genetic testing, ultimately providing more accurate information for family members. Preaxial involvement of the upper extremities was a significant discriminating limb‐specific variable in our analysis of genetically mapped SHFM cases. This finding, which was originally identified through descriptive epidemiology, was subsequently confirmed by discriminant function analysis (p < 0.0001) to be a significant locus discriminator. Preaxial involvement of the upper extremities was most commonly seen at the SHFM3 locus mapped to chromosome 10q24 (OMIM 600095) and consisted of proximally placed thumbs and/or triphalangeal thumbs (TPT), preaxial polydactyly and/or absence of the first ray. These patients' feet, however, tended to show a classical central longitudinal deficiency without a significant preaxial component. This article discusses this discrepant clefting pattern between the upper and lower extremities and proposes potential mechanisms.
Recurrent trisomy 21: four cases in three generations
Authors: Gair JL , Arbour L , Rupps R , Jiang R , Bruyère H , Robinson WP
Published: August 2005

While gonadal mosaicism can lead to recurrence of trisomy 21 (T21) for a single couple, the recurrence of free T21 in multiple members of a single pedigree has rarely been reported. We present an unusual pedigree with four cases of Down syndrome (DS) with free T21 were born to four separate women related through three generations of one family. The mothers were aged 18, 21, 29, and approximately 30 years at the time of the births. Using microsatellite markers, we excluded most of chromosome 21, excepting two small regions within 21q11.1 and 21q22.3, as being shared among the mothers of the DS children. However, two members of the pedigree, including one DS mother with a normal G‐banded karyotype, carried supernumerary alleles at markers 2503J9TG, D21S369, and D21S215, which span the region from 21pter to 21q11.1. Fluorescence in situ hybridization using a centromeric probe hybridizing to chromosomes 13 and 21 did not reveal a novel location, ruling out a cryptic centromeric translocation between chromosome 21 and any chromosome other than chromosome 13. The level of meiotic recombination on chromosome 21 was unusually high in this family as well. We hypothesize that a cryptic rearrangement within the highly repetitive region of 21q11.1 is present in this family, disrupting pairing and leading to an increased risk of non‐disjunction of chromosome 21 in this family.
Functional assessment of immune markers of graft rejection: a comprehensive study in live‐related donor renal transplantation
Authors: Panigrahi A , Deka R , Bhowmik D , Dash SC , Tiwari SC , Guleria S , Mehta SN , Mehra NK
Published: September 2005

Abstract:  A better understanding of the immunobiological processes and predictors of graft rejection holds promise for the development of potential therapeutic strategies and also individualization of immunosuppression. The objective of this study is to analyze the clinical relevance of immune parameters such as antidonor antihuman leukocyte antigen (anti‐HLA) antibodies, monitoring of cytokines and their receptors on the graft outcome following live‐related donor renal transplantation. Flow cytometry‐based methods were used to detect antidonor antibodies (flow cytometry crossmatch, FCXM) and intracellular cytokines. Enzyme‐linked immunosorbent assay (ELISA) methods were employed to detect anti‐HLA class I and class II antibodies and quantitative serum‐soluble interleukin‐2 receptor (sIL‐2R) levels. The data revealed that patients with HLA class I‐specific IgG antibody experienced higher acute rejection (AR) episodes at 1 yr in comparison to the antibody negative group (82% vs. 56%, p = 0.01). On the contrary, donor‐specific class II antibodies (B+) did not have any influence on the graft survival. However, 15 recipients having both T‐ and B‐cell antidonor antibodies (T+B+) had significantly poor graft survival (60%) as compared to the antibody‐negative group (T−B−, 82%, p = 0.05). Additionally, patients having non‐donor but HLA‐specific antibodies (FCXM−/ELISA+) had poor graft survival as compared to the antibody‐negative group (64% vs. 88%, p < 0.05). Further, patients undergoing AR episodes had significantly higher expression of IFN‐γ‐producing T cells (19.16 ± 7.4% median 17.50) as compared to their pre‐transplant levels (5.68 ± 1.63%, Median 5.20) and the non‐rejecter group (5.97 ± 4.39%, median 4.3, p = 0.0004). Similarly sIL‐2 was significantly increased in AR episodes during the first month of transplantation (292 ± 131.5 pmol/L) as compared to those with well‐functioning grafts (p = 0.01) and healthy controls (p = 0.001). Evaluation of antidonor antibodies by flow cytometry is found to be relatively more sensitive and a better predictor of graft outcome. Further monitoring of cytokine expression profile of primed peripheral T‐helper cells and quantitative analysis of sIL‐2R offer additional valuable diagnostic and prognostic tools for follow‐up of transplant subjects and a better alternative for functional assessment of immunosuppression.
The impact of donor spontaneous intracranial haemorrhage vs. other donors on long‐term renal graft and patient survival
Authors: Johnston Olwyn , O'Kelly Patrick , Spencer Susan , Cunningham Phyllis , Dorman Anthony , Donohoe John , Walshe Joseph J , Hickey David , Little Dilly M , Conlon Peter J
Published: September 2005

Abstract:  Background:  Donor cause of death has a significant impact on transplant survival in heart transplants recipients. The objective of this study was to determine if long‐term renal allograft and patient survival differed between grafts donated by donors who died of spontaneous intracranial haemorrhage (SIH) compared with those with other causes of death (OCOD).

Methods:  Between 1990 and 2001, 1526 renal transplants were performed (711 SIH donors and 815 OCOD donors) at our unit. Serum creatinine levels at 1 yr, graft half‐life and annual graft failure rate were measured for both groups. Renal graft and patient survivals between the groups were compared. Relative risk for SIH donors and other confounding variables was measured using Cox proportional hazards models.

Results:  Graft half‐life results were obtained for SIH (8 yr) and OCOD (10.13 yr) recipients. Graft and patient survival at 5 and 10 yr was 68.5% and 39.3% respectively for the SIH group vs. 76.8% and 51.9% respectively for the OCOD group (p < 0.001). However, SIH graft recipients were significantly older with more females. After adjustment for differences in baseline variables between the groups, donor cause of death did not have an independent effect on long‐term graft or patient survival.

Conclusion:  Spontaneous intracranial haemorrhage as a cause of donor death, failed to have a significant independent effect on long‐term allograft and patient survival.
Androgen‐binding Protein is Co‐Expressed with Oxytocin in the Male Reproductive Tract
Authors: Herbert Z. , Weigel S. , Sendemir E. , Marshall A. , Caldwell J. D. , Petrusz P. , Peuckert C. , Jirikowski G. F.
Published: August 2005

Androgen‐binding protein (ABP) and the posterior lobe hormone oxytocin (OT) were co‐localized in male rat reproductive organs. Immunostaining of serial semi‐thin sections revealed a high rate of coexistence of both antigens in Sertoli cells and in the epithelial cells of the prostate. There was a considerably less co‐localization of OT and ABP in epithelial cells of the epididymis, and in the different tissues of the ductus deferens. In situ hybridization with synthetic oligonucleotides complementary to a fragment of ABP mRNA showed specific staining in the same sites that were immunostained for ABP. ABP was isolated by affinity chromatography from homogenates of testis, epididymis, prostate and the content of the prostate lumen. Identical protein patterns could be shown with surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry in all samples except for the epididymis indicating that ABP structure is similar in all these tissues. ABP seems to be expressed in specified cells throughout the male rat reproductive tract. Most of these cells appear to be oxytocinergic. ABP and OT have previously been detected in the ejaculate. The observed epithelial cells are likely to be their source.
Effects of Fusarium toxin‐contaminated wheat grain on nutrient turnover, microbial protein synthesis and metabolism of deoxynivalenol and zearalenone in the rumen of dairy cows
Authors: Dänicke S. , Matthäus K. , Lebzien P. , Valenta H. , Stemme K. , Ueberschär K.‐H. , Razzazi‐Fazeli E. , Böhm J. , Flachowsky G.
Published: August 2005

The aim of the present study was to examine the effects of feeding Fusarium toxin‐contaminated wheat to dairy cows on nutrient utilization in the rumen and on duodenal flow of deoxynivalenol (DON), zearalenone (ZON) and their metabolites. Six dairy cows fitted with a large rumen cannula and a simple T‐shaped cannula at the proximal duodenum was used in two experiments. The experiments included a control period in which the uncontaminated control wheat was fed and a period in which the control wheat was replaced by the Fusarium toxin‐contaminated wheat (8.05 and 7.15 mg DON/kg and 0.26 and 0.1 mg ZON/kg in Expts 1 and 2 respectively). The wheat portion of the daily ration amounted to 50% on a dry matter (DM) basis and rations were completed with hay or grass silage. Five of the six cows were non‐lactating and the total daily DM‐intake ranged between 4 and 12 kg. The pH‐values and the concentration of volatile fatty acids in ruminal fluid were not significantly influenced by feeding the contaminated wheat. In contrast, the postprandial ammonia concentration was consistently higher when the mycotoxin‐contaminated wheat was fed. Moreover, the flow of microbial protein and utilizable protein at the duodenum were reduced at the same time. The concentrations of DON and ZON and of their metabolites in freeze‐dried duodenal digesta were either not detectable or negligible during the control periods whereas distinct concentrations were measured during the periods where the contaminated wheat was fed. DON was nearly completely metabolized to de‐epoxy‐DON and the flow at the duodenum ranged between 4% and 28% of DON‐intake. The ZON metabolites α‐zearalenol (ZOL) and β‐ZOL were recovered at the duodenum beside the parent toxin ZON. Their recovery as a percentage of ZON‐intake ranged between 43% and 132%. In conclusion, feeding of Fusarium toxin‐contaminated wheat altered the ruminal protein utilization. The question of whether this effect was a result of the mycotoxin being present in the rumen or of Fusarium growth‐related structural (cell wall) changes of the wheat grain needs to be clarified. The low recovery of DON at the duodenum would indicate either a nearly complete degradation of the molecule in the rumen or an absorption by the mucosa of the rumen, whereas the higher ZON recovery would suggest a lower degradation of the parent toxin in the rumen and/or recovery of some bile‐originating entero‐hepatic cycling ZON/metabolites.