bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Prenatal Lipopolysaccharide Exposure on Epithelial Development and Function in Newborn Rat Intestine
Authors: Giannone Peter J. , Schanbacher Brandon L. , Bauer John A. , Reber Kristina M.
Published: September 2006

Background:

Maternal infection during pregnancy is associated with several neonatal morbidities, including periventricular leukomalacia and lung maldevelopment and injury.

Objective:

To test the hypothesis that responses to prenatal maternal exposure to lipopolysaccharide (LPS) alter intestinal epithelial development and function in newborn rats.

Design/Methods:

Timed‐pregnancy female Sprague‐Dawley rats were administered either 2 mg LPS or an equal volume of isotonic saline by intraperitoneal injection at E16 and allowed to deliver naturally. Pups were weighed and then killed at days of life (DOL) 0, 3, 7 and 14. Morphometric parameters were measured on standard hematoxylin and eosin‐stained sections using ImagePro software. Immunohistochemistry was performed with antibody specific for inducible nitric oxide synthase (iNOS) and 3‐nitrotyrosine on distal ileal intestinal samples analyzed at each time point. Optical density was determined and quantified for site‐specific regions of intestinal sections. On DOL 14, in vivo mucosal permeability was measured by feeding rats fluorescein isothiocyanate (FITC) via orogastric tube; and then serum FITC was measured.

Results:

There were no significant differences in pup weights. Mucosal thicknesses were significantly less in the distal ileum from pups born to LPS‐exposed dams on DOL 0, 3 and 7 (P < 0.001). On DOL 0, iNOS protein concentrations in the prenatal LPS treatment group were significantly greater than iNOS protein concentrations in the distal villus (P < 0.001), proximal villus/crypts (P < 0.01), submucosa (P < 0.001) and muscularis (P < 0.01) in the distal small intestine of the control group. On DOL 3, 7 and 14, significant differences were observed in iNOS protein concentrations in the distal villus and submucosal regions between groups (P < 0.001). On DOL 0, 3, 7 and 14, 3‐nitrotyrosine immunostaining was significantly elevated in the prenatal LPS‐exposed pups in the distal villus on (P < 0.001) as well as in the submucosa on DOL 3 (P < 0.001). Serum FITC measurement was significantly greater in prenatal LPS exposure group at DOL 14 (P < 0.001).

Conclusions:

Maternal exposure to LPS during pregnancy alters intestinal growth and regulation of iNOS in the newborn rat intestine.
Relationship Between Viral Load and Genotypes of Hepatitis B Virus in Children With Chronic Hepatitis B
Authors: Oommen Prasad T. , Wirth Stefan , Wintermeyer Philip , Gerner Patrick
Published: September 2006

Objective:

We evaluated the prevalence and clinical significance of hepatitis B virus (HBV) genotypes in children with chronic hepatitis B.

Methods:

Hepatitis B virus genomes of 249 hepatitis Be antigen‐positive chronic hepatitis B surface antigen carriers were genotyped based on restriction fragment length polymorphism. Genotypes were correlated with corresponding values for alanine aminotransferase levels, quantitative HBV DNA and histological findings.

Results:

One hundred and sixty‐two boys and 87 girls (mean age, 7.2 years) were studied. Ninety‐six percent were attributed to HBV genotypes A (32.5%) or D (63.5%). The remaining were classified as genotypes B, C, E and F. There was no significant difference in both alanine aminotransferase levels and histological findings among different genotypes. However, there was a clear association between very high HBV DNA levels and individuals with genotype D (P = 0.006). Mean time follow‐up of 3.6 years showed later anti‐HBe seroconversion in patients with genotype D than in those with genotype A (58% vs 37%).

Conclusions:

Compared with children with genotype A, children with genotype D showed a significantly higher viral load. Inasmuch as a relationship exists between viral load and response to treatment in children infected through vertical transmission, children with genotype D have to be carefully monitored. Long‐term studies are needed to determine whether these patients are at risk of a poorer outcome.
Paternity loss in contrasting mammalian societies
Authors: Clutton-Brock T.H , Isvaran K
Published: September 2006

Recent genetic analyses show that, in social mammals, loss of paternity by breeding males varies with strategies of mate guarding rather than with the degree of polygyny.
Material properties of brachiopod shell ultrastructure by nanoindentation
Authors: Pérez-Huerta Alberto , Cusack Maggie , Zhu Wenzhong , England Jennifer , Hughes John
Published: September 2006

Mineral-producing organisms exert exquisite control on all aspects of biomineral production. Among shell-bearing organisms, a wide range of mineral fabrics are developed reflecting diverse modes of life that require different material properties. Our knowledge of how biomineral structures relate to material properties is still limited because it requires the determination of these properties on a detailed scale. Nanoindentation, mostly applied in engineering and materials science, is used here to assess, at the microstructural level, material properties of two calcite brachiopods living in the same environment but with different modes of life and shell ultrastructure. Values of hardness (H) and the Young modulus of elasticity (E) are determined by nanoindentation. In brachiopod shells, calcite semi-nacre provides a harder and stiffer structure (H∼3–6 GPa;E=60–110/120 GPa) than calcite fibres (H=0–3 GPa;E=20–60/80 GPa). Thus, brachiopods with calcite semi-nacre can cement to a substrate and remain immobile during their adult life cycle. This correlation between mode of life and material properties, as a consequence of ultrastructure, begins to explain why organisms produce a wide range of structures using the same chemical components, such as calcium carbonate.
Neutral fitness landscapes in signalling networks
Authors: Fernández Pau , Solé Ricard V
Published: September 2006

Biological and technological systems process information by means of cascades of signals. Be they interacting genes, spiking neurons or electronic transistors, information travels across these systems, producing, for each set of external conditions, an appropriate response. In technology, circuits performing specific complex tasks are designed by humans. In biology, however, design has to be ruled out, confronting us with the question of how these systems could have arisen by accumulation of small changes. The key factor is the genotype–phenotype map. With the exception of RNA folding, not much is known about the exact nature of this mapping. Here, we show that structure of the genotype–phenotype map of simple feed-forward circuits is very close to the ones found in RNA; they have a large degree of neutrality, by which a circuit can be completely rewired keeping its input–output function intact, and there is a relatively small neighbourhood of a given circuit containing almost all the phenotypes.
Escalated conflict in a social hierarchy
Authors: Cant M.A , English S , Reeve H.K , Field J
Published: September 2006

Animals that live in cooperative societies form hierarchies in which dominant individuals reap disproportionate benefits from group cooperation. The stability of these societies requires subordinates to accept their inferior status rather than engage in escalated conflict with dominants over rank. Applying the logic of animal contests to these cases predicts that escalated conflict is more likely where subordinates are reproductively suppressed, where group productivity is high, relatedness is low, and where subordinates are relatively strong. We tested these four predictions in the field on co-foundress associations of the paper waspPolistes dominulusby inducing contests over dominance rank experimentally. Subordinates with lower levels of ovarian development, and those in larger, more productive groups, were more likely to escalate in conflict with their dominant, as predicted. Neither genetic relatedness nor relative body size had significant effects on the probability of escalation. The original dominant emerged as the winner in all except one escalated contest. The results provide the first evidence that reproductive suppression of subordinates increases the threat of escalated conflict, and hence that reproductive sharing can promote stability of the dominant–subordinate relationship.
Outcome expectations drive learned behaviour in larval
Drosophila
Authors: Gerber Bertram , Hendel Thomas
Published: September 2006

Why does Pavlov's dog salivate? In response to the tone, or in expectation of food? While in vertebrates behaviour can be driven by expected outcomes, it is unknown whether this is true for non-vertebrates as well. We find that, in the
Drosophila
larva, odour memories are expressed behaviourally only if animals can expect a positive outcome from doing so. The expected outcome of tracking down an odour is determined by comparing the value of the current situation with the value of the memory for that odour. Memory is expressed behaviourally only if the expected outcome is positive. This uncovers a hitherto unrecognized evaluative processing step between an activated memory trace and behaviour control, and argues that learned behaviour reflects the pursuit of its expected outcome. Shown in a system with a simple brain, an apparently cognitive process like representing the expected outcome of behaviour seems to be a basic feature of behaviour control.
An experimental test of the contributions and condition dependence of microstructure and carotenoids in yellow plumage coloration
Authors: Shawkey Matthew D , Hill Geoffrey E , McGraw Kevin J , Hood Wendy R , Huggins Kristal
Published: September 2006

A combination of structural and pigmentary components is responsible for many of the colour displays of animals. Despite the ubiquity of this type of coloration, neither the relative contribution of structures and pigments to variation in such colour displays nor the relative effects of extrinsic factors on the structural and pigment-based components of such colour has been determined. Understanding the sources of colour variation is important because structures and pigments may convey different information to conspecifics. In an experiment on captive American goldfinchesCarduelis tristis, we manipulated two parameters, carotenoid availability and food availability, known to affect the expression of carotenoid pigments in a full-factorial design. Yellow feathers from these birds were then analysed in two ways. First, we used full-spectrum spectrometry and high-performance liquid chromatography to examine the extent to which variation in white structural colour and total carotenoid content was associated with variation in colour properties of feathers. The carotenoid content of yellow feathers predicted two colour parameters (principal component 1—representing high values of ultraviolet and yellow chroma and low values of violet–blue chroma—and hue). Two different colour parameters (violet–blue and yellow chroma) from white de-pigmented feathers, as well as carotenoid content, predicted reflectance measurements from yellow feathers. Second, we determined the relative effects of our experimental manipulations on white structural colour and yellow colour. Carotenoid availability directly affected yellow colour, while food availability affected it only in combination with carotenoid availability. None of our manipulations had significant effects on the expression of white structural colour. Our results suggest that the contribution of microstructures to variation in the expression of yellow coloration is less than the contribution of carotenoid content, and that carotenoid deposition is more dependent on extrinsic variability than is the production of white structural colour.
Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven families with erythropoietic protoporphyria
Authors: SARUWATARI Hiroshi , UEKI Yuri , YOTSUMOTO Shinichi , SHIMADA Tokihiko , FUKUMARU Seita , KANEKURA Takuro , KANZAKI Tamotsu
Published: September 2006

A decrease in the activity of ferrochelatase (FECH; EC 4.99.1.1), the terminal enzyme of the heme biosynthetic pathway, results in erythropoietic protoporphyria (EPP; MIM 177000). We analyzed the FECHgene in eight Japanese EPP patients from seven non‐consanguineous families and found two distinct genomic DNA abnormalities. In six patients from five families, there was a G‐to‐A point‐mutation at the first position of the intron 9 donor site; it resulted in aberrant splicing and skipping of exon 9 in FECH mRNA. In one patient, we found an A‐to‐G point‐mutation 4 bases from the 3" terminus of intron 4 that led to the in‐frame insertion of 3 bases in mRNA. No allelic anomalies, except for 3 single nucleotide polymorphisms were detected in another patient. We analyzed intron polymorphism at IVS3‐48, known to be associated with the phenotypic expression of EPP, in these eight patients and 152 healthy Japanese volunteers. All patients were C/C homozygous for IVS3‐48. The allelic frequency of IVS3‐48C polymorphism in the healthy Japanese volunteers was 67.8% (103/152).
Differential expression of matrix metalloproteinase‐2 by fibroblasts in co‐cultures with keratinocytes, basal cell carcinoma and melanoma
Authors: CHEN Gwo‐Shing , LU Mei‐Pao , WU Meng‐Tse
Published: September 2006

To address whether matrix metalloproteinase (MMP)‐2 expression by mesenchymal fibroblasts may be differentially modulated by interactions with normal or malignant epidermal cells, we set up a fibroblast co‐culture model separately with keratinocytes, basal cell carcinoma cells and melanoma cells. Real‐time reverse transcription polymerase chain reaction (RT–PCR) and gelatin zymography were used to detect and quantify the expression of MMP‐2 by these different kinds of cells. In independent cultures, MMP‐2 was highly expressed by fibroblasts and melanoma cells constitutively, but barely expressed by keratinocytes and basal cell carcinoma (BCC) cells. MMP‐2 expression by fibroblasts was downregulated in co‐cultures with keratinocytes or BCC cells, but not with melanoma cells. These results indicate that epidermal–mesenchymal interactions are important modulators for MMP‐2 expression by cutaneous cells and suggest a host‐defense mechanism against the tumor progression of BCC.
Chronic pulmonary complications associated with toxic epidermal necrolysis: Report of a severe case with anti‐Ro/SS‐A and a review of the published work
Authors: KAMADA Noriaki , KINOSHITA Kyoko , TOGAWA Yaei , KOBAYASHI Takashi , MATSUBARA Hiroshi , KOHNO Masakazu , IGARI Hidetoshi , KURIYAMA Takayuki , NAKAMURA Masataka , HIRASAWA Hiroyuki , SHINKAI Hiroshi
Published: September 2006

Patients with toxic epidermal necrolysis (TEN) have been known to have various complications. Though pulmonary complications are often observed, they usually show an acute form; however, chronic complications are quite rare and little is known about either their incidences or clinical manifestations. We herein report a 33‐year‐old man who presented with chronic pulmonary complications after a recovery from TEN. At the onset of TEN, he had severe respiratory failure and artificial ventilation was instituted. Despite being extubated successfully, respiratory failure reappeared 1 month later. A diagnosis of chronic bronchitis with severe obstructive ventilatory impairment and bronchiectasis was made and he was treated with steroids, bronchodilators and antibiotics, however, he died 1.5 years after the onset of TEN. There have been 13 reported cases of chronic pulmonary complications with TEN or Stevens–Johnson syndrome (SJS) in the English published work. Such cases are usually classified into chronic bronchitis/bronchiolitis with obstructive change (including bronchiolitis obliterans and bronchiolitis obliterans organizing pneumonia), respiratory tract obstruction and bronchiectasis. Approximately 40% of all such patients die while the surviving continue to suffer from these complications because no curative therapy yet exists. As a result, the prognosis seems to be poor. The relationship between TEN and these chronic pulmonary complications remains to be elucidated. Interestingly, our patient was asymptomatically anti‐Ro/SS‐A positive at the onset of TEN. In addition, eccrine gland involvement and an extremely high level of serum salivary amylase were observed at the onset of TEN, furthermore, Sjögren‐like symptoms occurred after recovery from TEN. These findings suggested that the Sjögren‐like autoimmune abnormalities induced by anti‐Ro/SS‐A correlated with the development of chronic pulmonary complications in our patient.
Clinical trial of a laser device called fractional photothermolysis system for acne scars
Authors: HASEGAWA Toshio , MATSUKURA Tomoyuki , MIZUNO Yuki , SUGA Yasushi , OGAWA Hideoki , IKEDA Shigaku
Published: September 2006

Ablative laser resurfacing is an effective treatment for acne scars. However, edema and prolonged erythema are common. Additionally, scarring and hyperpigmentation are often induced. A new concept of laser called fractional photothermolysis has been designed to create microscopic thermal wounds to achieve skin rejuvenation without significant side‐effects. We treated 10 patients with acne scars using this laser system (Reliant Fraxel SR Laser). All the patients were successfully treated with minimal adverse effects. The fractional photothermolysis system represents an optional method for the treatment of acne scars.
Segmental neurofibromatosis: Report of two cases
Authors: SEZER Engin , SENAYLI Atilla , SEZER Taner , BICAKCI Unal
Published: September 2006

Neurofibromatosis (NF), or von Recklinghausen's disease is comprised of a heterogeneous group of disorders, primarily affecting the skin, soft tissue, bone and central nervous system. Segmental neurofibromatosis (SN) is a rare form of NF, characterized by “café‐au‐lait” macules, freckles, and/or neurofibromas limited to a body segment. There are approximately 150 cases reported in the English published work. Bilateral segmental neurofibromatosis is a rare subtype of SN, manifesting with bilateral involvement of the body segments. Herein, we report two patients with SN; one associated with pectus excavatum, and the other case diagnosed as bilateral segmental neurofibromatosis. Asymmetry of the skull and thorax, kyphoscoliosis and segmental bone hypertrophy of the leg are skeletal abnormalities previously reported with SN. To the best of our knowledge, this is the first case of SN in association with pectus excavatum.
Diagnostic utility of aberrant methylation of tissue factor pathway inhibitor 2 in pure pancreatic juice for pancreatic carcinoma
Authors: Jiang PeiHong , Watanabe Hiroyuki , Okada Gensaku , Ohtsubo Koushiro , Mouri Hisatsugu , Tsuchiyama Tomoya , Yao Fan , Sawabu Norio
Published: September 2006

The tissue factor pathway inhibitor 2 (TFPI‐2) is a Kunitz‐type serine proteinase inhibitor. Recently, the aberrant methylation of TFPI‐2 was detected frequently in pancreatic carcinoma (PCa) tissues but not in normal pancreatic tissues. We analyzed the aberrant methylation of TFPI‐2 in the pure pancreatic juice (PPJ) aspirated endoscopically from patients with various pancreatic diseases. Using the highly sensitive methylation‐specific polymerase chain reaction (MSP) and quantitative MSP (Q‐MSP) assay, we investigated the aberrant methylation of TFPI‐2 in nine human PCa cell lines and in the PPJ from patients with PCa, intraductal papillary mucinous neoplasms (IPMN) and chronic pancreatitis (CP). The incidence of aberrant TFPI‐2 methylation was seven (77.8%) of nine PCa cell lines by Q‐MSP. In cell lines, the expression of TFPI‐2 mRNA by quantitative reverse transcription–polymerase chain reaction showed an inverse correlation to the aberrant methylation of TFPI‐2. The incidence of aberrant TFPI‐2 methylation in the PPJ was 21 (58.3%) of 36 PCa patients, three (17.6%) of 17 IPMN and one (4.8%) of 21 CP by MSP assay. Using a suitable cut‐off value of 2.5 according to the receiver operating characteristic curve, the incidence of aberrant TFPI‐2 methylation in the PPJ by real‐time MSP was 18 (62.1%) of 29 PCa patients, one (5.1%) of 17 IPMN and three (14.3%) of 21 CP, respectively. The incidence of quantitative TFPI‐2 hypermethylation in the PPJ with PCa was significantly higher than that with IPMN (P < 0.001) or CP (P < 0.001). Moreover, the aberrant methylation rate of TFPI‐2 in the PPJ was 100%, as observed (6/6) in the PCa patients with liver metastasis, and 86.7% (26/30) in stages IVa + IVb of PCa by Q‐MSP assay. These results suggest that promoter methylation of TFPI‐2 in the PPJ may be a useful marker in the diagnosis and progression of PCa using an endoscopically feasible approach. (Cancer Sci 2006; 97: 1267–1273)
EphA4 receptor, overexpressed in pancreatic ductal adenocarcinoma, promotes cancer cell growth
Authors: Iiizumi Megumi , Hosokawa Masayo , Takehara Akio , Chung Suyoun , Nakamura Toru , Katagiri Toyomasa , Eguchi Hidetoshi , Ohigashi Hiroaki , Ishikawa Osamu , Nakamura Yusuke , Nakagawa Hidewaki
Published: September 2006

To isolate novel diagnostic markers and drug targets for pancreatic ductal adenocarcinoma (PDAC), we previously performed expression profile analysis of PDAC cells using a genome‐wide cDNA microarray combined with laser microdissection. Among dozens of up‐regulated genes identified in PDAC cells, we herein focused on one tyrosine kinase receptor, Eph receptor A4 (EphA4), as a molecular target for PDAC therapy. Immunohistochemical analysis validated EphA4 overexpression in approximately half of the PDAC tissues. To investigate its biological function in PDAC cells, we knocked down EphA4 expression by siRNA, which drastically attenuated PDAC cell viability. In concordance with the siRNA experiment, PDAC‐derivative cells that were designed to constitutively express exogenous EphA4 showed a more rapid growth rate than cells transfected with mock vector, suggesting a growth‐promoting effect of EphA4 on PDAC cells. Furthermore, the expression analysis for ephrin ligand family members indicated the coexistence of ephrinA3 ligand in PDAC cells with EphA4 receptor, and knockdown of ephrinA3 by siRNA also attenuated PDAC cell viability. These results suggest that the EphA4–ephrinA3 pathway is likely to be a promising molecular target for pancreatic cancer therapy. (Cancer Sci 2006; 97: 1211–1216)
The global nitrogen regulator, FNR1, regulates fungal nutrition‐genes and fitness during Fusarium oxysporum pathogenesis
Authors: DIVON HEGE HVATTUM , ZIV CARMIT , DAVYDOV OLGA , YARDEN ODED , FLUHR ROBERT
Published: September 2006

Fusarium oxysporum is a soil‐borne pathogen that infects plants through the roots and uses the vascular system for host ingress. Specialized for this route of infection, F. oxysporum is able to adapt to the scarce nutrient environment in the xylem vessels. Here we report the cloning of the F. oxysporum global nitrogen regulator, Fnr1, and show that it is one of the determinants for fungal fitness during in planta growth. The Fnr1 gene has a single conserved GATA‐type zinc finger domain and is 96% and 48% identical to AREA‐GF from Gibberella fujikuroi, and NIT2 from Neurospora crassa, respectively. Fnr1 cDNA, expressed under a constitutive promoter, was able to complement functionally an N. crassa nit‐2RIP mutant, restoring the ability of the mutant to utilize nitrate. Fnr1 disruption mutants showed high tolerance to chlorate and reduced ability to utilize several secondary nitrogen sources such as amino acids, hypoxanthine and uric acid, whereas growth on favourable nitrogen sources was not affected. Fnr1 disruption also abolished in vitro expression of nutrition genes, normally induced during the early phase of infection. In an infection assay on tomato seedlings, infection rate of disruption mutants was significantly delayed in comparison with the parental strain. Our results indicate that FNR1 mediates adaptation to nitrogen‐poor conditions in planta through the regulation of secondary nitrogen acquisition, and as such acts as a determinant for fungal fitness during infection.
Increased expression of collagen receptors: α1β1 and α2β1 integrins on blood eosinophils in bronchial asthma
Authors: Bazan‐Socha S. , Bukiej A. , Pulka G. , Marcinkiewicz C. , Musial J.
Published: September 2006

Background
Eosinophils are one of the major effector cells in bronchial asthma. Their infiltration of airways correlates with the asthma severity. Recruitment and activation of eosinophils are partially mediated by integrins α4β1 and α4β7. Collagens type I and IV constitute important components of extracellular matrix and vascular basement membrane, respectively. Therefore, collagen‐binding integrins (α1β1 and α2β1) may also play a role in eosinophil lung infiltration.

Objective
To evaluate the possible presence of α1β1 and α2β1 integrins on peripheral blood eosinophils from asthmatic subjects.

Methods
Collagen receptors were studied on eosinophils separated by immunomagnetic CD16‐negative method from healthy donors (n=13) and patients with moderate persistent atopic bronchial asthma (n=15). Surface receptor identification was performed by flow cytometry and cell adhesion assay.

Results
Eosinophils isolated from the patients showed increased expression of both α1β1 and α2β1 integrins as compared with healthy controls. Moreover, adhesive function of eosinophils to collagen type IV was inhibited by snake venom disintegrins: viperistatin and obtustatin. These disintegrins contain KTS active motif and are specific inhibitors of α1β1 integrin.

Conclusion
We demonstrated for the first time that collagen receptors: α1β1 and α2β1 integrins are overexpressed on the surface of peripheral blood eosinophils of asthmatic subjects. Further studies may reveal potential application of KTS‐disintegrins or their structural analogs for therapy of bronchial asthma.
Airborne exposure to wheat allergens: measurement by human immunoglobulin G4 and rabbit immunoglobulin G immunoassays
Authors: Bogdanovic J. , Wouters I. M. , Sander I. , Raulf‐Heimsoth M. , Elms J. , Rodrigo M. J. , Heederik D. J. J. , Doekes G.
Published: September 2006

Background: Exposure to airborne wheat allergens in the bakery trade is associated with a high risk of occupational allergy and asthma. Control and reduction of allergen exposure require relatively simple but reliable monitoring techniques. We developed new rabbit IgG‐based enzyme immunoassays (EIA) for wheat allergens, which might be a convenient alternative for the thus far used human IgG4 inhibition assay.

Methods: The reactivity and specificity of rabbit antibodies were assessed by EIA and immunoblotting, and compared with those of IgE from wheat‐sensitized bakers, and with the antibodies used in the IgG4 inhibition EIA. An IgG inhibition and a sandwich EIA were developed for analysis of airborne dust samples.

Results: Human IgG4 and rabbit IgG inhibition EIAs had comparable sensitivities, with limits of detection (LOD) between 18 and 88 ng/mL, while the sandwich EIA was much more sensitive (LOD<0.2 ng/mL). Human IgG4 and rabbit IgG reacted in immunoblotting with most of the IgE‐binding wheat proteins, although with quantitative differences. All three assays showed a strong reaction with wheat proteins, and some cross‐reactivity with rye and barley, but were further highly specific for cereal flour proteins. Concentrations measured with the three EIAs in 432 airborne dust samples were highly correlated (r>0.95) and their absolute values showed less than 10–20% differences.

Conclusion: The rabbit IgG EIAs are valid substitutes for the human IgG4 inhibition EIA, with important practical advantages. The inhibition EIA is recommended for routine wheat allergen measurements. The sandwich EIA may be used to measure low allergen levels, as in short task‐related exposure measurements or in subfractions of airborne dust samples.
Relationship between neurokinin 2 receptor gene polymorphisms and serum vascular endothelial growth factor levels in patients with toluene diisocyanate‐induced asthma
Authors: Ye Y.‐M. , Kang Y.‐M. , Kim S.‐H. , Kim C.‐W. , Kim H.‐R. , Hong C.‐S. , Park C.‐S. , Kim H.‐M. , Nahm D.‐H. , Park H.‐S.
Published: September 2006

Background
Among the various pathogenic mechanisms of toluene diisocyanate (TDI)‐induced asthma, a contribution from neurogenic inflammation has been suggested.

Objective
To evaluate neurokinin 2 receptor (NK2R) gene polymorphisms in association with the clinical phenotype of TDI‐induced asthma, 70 TDI‐induced occupational asthma (TDI‐OA)patients, 59 asymptomatic exposed controls (AEC), and 93 unexposed healthy controls (NC) were enrolled in the study.

Methods
Two single‐nucleotide polymorphisms (SNPs) of NK2R, 7853G>A (Gly231Glu) and 11 424G>A (Arg375His), were genotyped using a single base extension method. The levels of PC20 methacholine, specific IgE and IgG to TDI–human serum albumin conjugate, and serum vascular endothelial growth factor (VEGF), matrix metalloproteinase‐9, and TGF‐β1 were compared according to the NK2R genotypes of the subjects with TDI‐OA and AEC.

Results
No significant differences in allele, genotype, or haplotype frequencies of these two SNPs were noted among the three groups (P>0.05, respectively). Moreover, subjects with the NK2R 7853GG genotype had higher serum VEGF levels than those with GA or AA among the TDI‐exposed workers (P=0.040).

Conclusion
The NK2R 7853GG genotype may contribute to increased serum VEGF levels, which result in airway inflammation after TDI exposure.
Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters
Authors: Pasquali M. , Baiardini I. , Rogkakou A. , Riccio A.M. , Gamalero C. , Descalzi D. , Folli C. , Passalacqua G. , Canonica G.W.
Published: September 2006

Background
Levocetirizine (LCZ) has been shown to be effective in allergic rhinitis. We evaluated its clinical efficacy, antinflammatory actions and its effects on quality of life (QoL) with a specific instrument in the asthma–rhinitis comorbidity.

Methods
Fifty adult patients with persistent rhinitis with/without asthma were enrolled. After a 1‐week run‐in for baseline evaluation, they were randomized to LCZ or placebo for 8 weeks. Cromolyn and salbutamol were permitted on demand. Rhinoconjunctivitis and asthma symptoms were evaluated by diary cards. QoL was assessed by the specific Rhinasthma questionnaire and the generic SF‐36 at different time‐points. Nasal scrapings and lavages were also performed for inflammatory cell count and mediator assessment.

Results
Ten patients dropped out for unrelated reasons and the remaining completed the study with no side‐effect. Symptoms began to decrease in the active group at the second week of treatment when the difference with the placebo group became significant (0.05) and so remained until the end of the trial. Starting from 2 weeks of therapy, there was a significant decrease vs. baseline in all the four components of the Rhinasthma questionnaire only in the active group. The intergroup comparison became significant (P<0.05) at 4 weeks. The SF‐36 detected only sporadic differences between groups. Eosinophils and neutrophils in nasal scraping were significantly decreased in the LCZ group vs. baseline at all times. Nasal mediators were under the detection limits and no analysis could be performed. In the active group, only two patients used rescue medications compared with 13 patients in the placebo group.

Conclusions
LCZ is clinically effective and capable of improving the rhinitis–asthma‐related QoL.
Airway hyper‐responsiveness in allergic asthma in guinea‐pigs is mediated by nerve growth factor via the induction of substance P: a potential role for trkA
Authors: De Vries A. , Engels F. , Henricks P. A. J. , Leusink‐Muis T. , McGregor G. P. , Braun A. , Groneberg D. A. , Dessing M. C. , Nijkamp F. P. , Fischer A.
Published: September 2006

Background: The neurotrophin nerve growth factor (NGF) has been implicated as a mediator in allergic asthma. Direct evidence that inhibition of NGF‐induced activation of neurotrophin receptors leads to improvement of airway symptoms is lacking. We therefore studied the effects of inhibitors of NGF signal transduction on the development of airway hyper‐responsiveness (AHR) and pulmonary inflammation in a guinea‐pig model for allergic asthma.

Methods: Airway responsiveness to the contractile agonist histamine was measured in vivo in guinea‐pigs that were sensitized and challenged with ovalbumin (OVA). Inflammatory cell influx and NGF levels were determined in bronchoalveolar lavage fluid (BALF). Substance P, a key mediator of inflammation, was measured in lung tissue by radioimmunoassay, while substance P immunoreactive neurons in nodose ganglia were measured by immunohistochemistry.

Results: OVA challenge induced an AHR after 24 h in OVA‐sensitized guinea‐pigs. This coincided with an increase in the amount of NGF in BALF. Simultaneously, an increase in the percentage of substance P immunoreactive neurons in the nodose ganglia and an increase in the amount of substance P in lung tissue were found. We used tyrosine kinase inhibitors to block the signal transduction of the high‐affinity NGF receptor, tyrosine kinase A (trkA). Treatment with the tyrosine kinase inhibitors (K252a or tyrphostin AG879) both inhibited the development of AHR, and prevented the increase in substance P in the nodose ganglia and lung tissue completely whereas both inhibitors had no effect on baseline airway resistance. Neither treatment with K252a or tyrphostin AG879 changed the influx of inflammatory cells in the BALF due to allergen challenge.

Conclusions: We conclude that substance P plays a role in the induction of AHR in our model for allergic asthma which is most likely mediated by NGF. As both tyrosine kinase inhibitors AG879 and K252a show a similar inhibitory effect on airway function after allergen challenge, although both tyrosine kinase inhibitors exhibit different non‐specific inhibitory effects on targets other than trkA tyrosine kinases, it is likely that the induction of substance P derived from sensory nerves is mediated by NGF via its high‐affinity receptor trkA.
Association of interferon‐γ and interferon regulatory factor 1 polymorphisms with asthma in a family‐based association study in Taiwan
Authors: Wang T.‐N. , Chu Y.‐T. , Chen W.‐Y. , Feng W.‐W. , Shih N.‐H. , Hsiang C.‐H. , Ko Y.‐C.
Published: September 2006

Background
Asthma is a multi‐factorial disorder caused by complex interactions between genetic and environmental factors. IFN‐γ and IFN regulatory factor 1 (IRF‐1) affect Th1/Th2 cytokine balance, and influence the differentiation of Th2 cells, which influence the development of asthma.

Objective
This study investigated CA repeats polymorphism of the IFN‐γ gene and GT repeats polymorphism of the IRF‐1 gene, which may predispose individuals to asthma pathogenesis.

Methods
In the present study, we used the transmission/disequilibrium test (TDT) to investigate the relationship between asthma and the IFN‐γ and IRF‐1 polymorphisms by studying 348 subjects composed of 232 parents and 116 asthmatic children.

Results
For global TDT test, IFN‐γ CA repeats and IRF‐1 GT repeat polymorphisms showed a significant association with asthma in children (P=0.009 and 0.017, respectively). We demonstrated that 13 CA repeats (138 bp) of IFN‐γ gene and 11 GT repeats (306 bp) of IRF‐1 gene are significantly preferentially transmitted to asthmatic children (T/NT=89/61, χ2=8.43, P<0.005 and T/NT=75/49, χ2=8.18, P<0.005, respectively). The offspring will have an increased risk of asthma when their parents transmit IFN‐γ 13 CA repeats (OR=1.83, P=0.009) and IRF1 11 GT repeats (OR=1.88, P=0.007) to them. But we observed that the IFN‐γ and IRF‐1 polymorphisms are not associated with IgE concentrations.

Conclusion
These findings provide strong evidence of which IFN‐γ CA repeat and IRF‐1 GT repeat polymorphisms influence the risk of asthma for children in Taiwan.
Identification of key peptide-specific CD4+ T cell responses to human cytomegalovirus: implications for tracking antiviral populations
Authors: Harcourt G C , Scriba T J , Semmo N , Bounds S , Taylor E , Klenerman P
Published: September 2006

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

Background  Iodide (I−) is crucial for foetal thyroid function. Foetal iodide results from maternal circulating iodide and from deiodination of iodothyronines within the placenta. The Na+/I− symporter (NIS) localized in placental cells appears to be involved in iodide exchange. Low NIS expression has been reported in trophoblast cells from the first trimester and pregnancy at term.

Aims  The aim of this study was to examine NIS expression by immunohistochemistry in the major components of human ovular tissue and placenta.

Materials and methods  Formalin‐fixed and paraffin‐embedded specimens of placental tissue from the first trimester and at term were analysed. NIS expression was quantified as percentage of NIS‐positive cells/total cells. NIS expression was also evaluated by real‐time polymerase chain reaction (RT‐PCR) in five first‐trimester and five at‐term placental specimens.

Results  In the first‐trimester specimens heterogeneous NIS immunoreactivity was found in cyto‐syncytiotrophoblast cells, with a range of NIS‐positive cells from 5% to 80% (mean ± SD 21·85 ± 23·95), in mesenchymal and endothelial cells from 1% to 40% (14·5 ± 11·16), in decidual cells from 5% to 40% (10·38 ± 11·98) and in endometrial glands from 3% to 40% (21·86 ± 13·93). In specimens from placenta at term, NIS‐positive cyto‐syncytiotrophoblast cells were between 5% and 40% (mean 17·85 ± 18·15), mesenchymal and endothelial cells between 1% and 40% (13·67 ± 12·16), decidual tissue between 5% and 30% (16·43 ± 9·08), and endometrial glands between 3% and 40% (16·67 ± 15·27). No significant differences in NIS expression were observed between the first trimester and placenta at term. A similar level of mRNA expression for the NIS gene was obtained by RT‐PCR both in ovular material of the first trimester and in placenta at term.

Conclusions  We found NIS to be expressed in various placental and ovular components and its expression to remain constant during pregnancy.
Management of amiodarone‐induced thyrotoxicosis in Latin America: an electronic survey
Authors: Diehl Leandro Arthur , Romaldini João Hamilton , Graf Hans , Bartalena Luigi , Martino Enio , Albino Claudio Cordeiro , Wiersinga Wilmar M.
Published: September 2006

Objective To assess diagnostic and therapeutic approaches to amiodarone‐induced thyrotoxicosis (AIT) among members of the Latin American Thyroid Society (LATS).

Methods LATS members responded to an online questionnaire that presented an index case (a 62‐year‐old man on amiodarone, with thyrotoxic symptoms and a nodular goitre) and a variant (same patient, no goitre).

Results About 25% of invited members responded to the questionnaire. Most respondents lived in iodine‐sufficient areas and observed that amiodarone‐induced hypothyroidism (AIH) is more common than AIT. Nearly all assessed TSH, and the most used combination of tests was TSH and free T4 (37%). Thyroid autoimmunity was assessed by about 90%. Interleukin‐6 (IL‐6) was useful to 80%. Additional tests ordered for the index case were: radioactive iodine uptake (RAIU; 57%), echo‐colour Doppler sonography (ECDS; about 50%) and fine‐needle aspiration biopsy (FNAB; 44%). For the variant, ECDS and RAIU were judged unhelpful by 16%. Most defined the index case as type I AIT and the variant as type II AIT, but 16% in LATS suggested a mixed form in the index case. As initial treatment, nearly all used thionamides in the index case [with potassium perchlorate (KClO4) in one‐third], while glucocorticoids were indicated to the variant by 66%. Only about 5% considered amiodarone withdrawal unnecessary. If initial strategy is ineffective in type I AIT, KClO4(half) or glucocorticoids (a third) are added; in type II, glucocorticoids are indicated by most. Once euthyroidism is restored, ablative therapy is prescribed by a third of respondents for type I AIT.

Conclusions There are several points of disagreement among thyroidologists regarding AIT management, mainly in the radiological evaluation and the approach to the already stabilized patient if amiodarone needs to be restarted.
11β Hydroxysteroid dehydrogenase type 1 is expressed and is biologically active in human skeletal muscle
Authors: Jang Christina , Obeyesekere Varuni R. , Dilley Rodney J. , Alford Frank P. , Inder Warrick J.
Published: September 2006

Objective  No data exist regarding the distribution and oxoreductase enzyme activity of 11β hydroxysteroid dehydrogenase type 1 (11β HSD‐1) in fresh human skeletal muscle. We aimed to investigate the mRNA and protein expression of 11β HSD‐1 in fresh skeletal muscle, confirm its biological activity and determine its relationship with hexose‐6‐phosphate dehydrogenase (H6PDH). We also examined the muscle fibre localization of 11β HSD‐1.

Design  Eleven non‐diabetic community volunteers underwent muscle biopsy of vastus lateralis.

Measurements  (i) 11β HSD‐1 and H6PDH mRNA expression by quantitative reverse transcription polymerase chain reaction (RT‐PCR); (ii) protein localization and fibre type specificity by immunohistochemistry; and (iii) enzyme oxoreductase activity by percentage conversion of 3H cortisone to cortisol.

Results  11β HSD‐1 mRNA was expressed at low levels compared to human liver. Mean ΔCT of skeletal muscle in 11 subjects was 19·57 (range 18·40–20·79) compared to ΔCT of 12·75 in human liver, which equates to an approximate 100‐fold higher level of expression. H6PDH mRNA was also detected with a mean ΔCT of 14·46 (range 13·13–16·60), approximately 35‐fold more abundant than 11β HSD‐1 in skeletal muscle. There was a significant correlation between 11β HSD‐1 and H6PDH (r = 0·67, P = 0·03). 11β HSD‐1 immunostaining was present in all muscle specimens, with similar distribution among fast and slow twitch fibres. 11β HSD‐1 oxoreductase activity was demonstrated, with mean conversion of cortisone to cortisol of 17·7% per 200 mg of muscle per 24 h (range 7·1–29·5%).

Conclusions  11β HSD‐1 mRNA and protein is expressed in fresh human skeletal muscle along with readily demonstrable oxoreductase activity. 11β HSD‐1 localization is not muscle fibre type specific. High levels of skeletal muscle H6PDH should ensure that oxoreductase activity predominates in vivo.
The story of socio‐technical design: reflections on its successes, failures and potential
Authors: Mumford Enid
Published: September 2006

Abstract.  This paper traces the history of socio‐technical design, emphasizing the set of values it embraces, the people espousing its theory and the organizations that practise it. Its role in the implementation of computer systems and its impact in a number of different countries are stressed. It also shows its relationship with action research, as a humanistic set of principles aimed at increasing human knowledge while improving practice in work situations. Its evolution in the 1960s and 1970s evidencing improved working practices and joint agreements between workers and management are contrasted with the much harsher economic climate of the 1980s and 1990s when such principled practices, with one or two notable exceptions, gave way to lean production, downsizing and cost cutting in a global economy, partly reflecting the impact of information and communications technology. Different future scenarios are discussed where socio‐technical principles might return in a different guise to humanize the potential impact of technology in a world of work where consistent organizational and economic change are the norm.
Why do female migratory birds arrive later than males?
Authors: KOKKO HANNA , GUNNARSSON TÓMAS G. , MORRELL LESLEY J. , GILL JENNIFER A.
Published: September 2006

In migratory birds males tend to arrive first on breeding grounds, except in sex‐role reversed species. The two most common explanations are the rank advantage hypothesis, in which male–male competition for breeding sites drives stronger selection for early arrival in males than females, and the mate opportunity hypothesis, which relies on sexual selection, as early arrival improves prospects of mate acquisition more for males than for females.

To date, theoretical work has focused on selection for early arrival within a single sex, usually male. However, if fitness depends on territory quality, selection for early arrival should operate on both sexes. Here we use two independent modelling approaches to explore the evolution of protandry (male‐first arrival) and protogyny (female‐first arrival) under the rank advantage and mate opportunity hypotheses.

The rank advantage hypothesis, when operating alone, fails to produce consistent patterns of protandry, despite our assumption that males must occupy territories before females. This is because an individual of either sex benefits if it out‐competes same‐sex competitors. Rather than promoting protandry, the rank advantage mechanism can sometimes result in protogyny. Female–female competition is stronger than male–male competition early in the season, if females compete for a resource (territories occupied by males) that is initially less common than the resource of interest to males (unoccupied territories).

Our results support the mate opportunity hypothesis as an explanation of why protandry is the norm in migratory systems. Male‐biased adult sex ratios and high levels of sperm competition (modelled as extra‐pair young: EPY) both produce protandry as a result of sexual selection. Protogyny is only observed in our models with female‐biased sex ratios and low EPY production.

We also show that the effects of sex ratio biases are much stronger than those of EPY production, explore the evidence for sex ratio biases and extra‐pair paternity in migratory species and suggest future research directions.