bluuebunny/crossref_metadata_2025 huggingface dataset:
Arsenic Species in a Rocky Intertidal Marine Food Chain in NSW, Australia, revisited
Authors: Foster Simon , Maher William , Schmeisser Ernst , Taylor Anne , Krikowa Frank , Apte Simon
Published: September 2006

Environmental Context. The pathways by which arsenic is accumulated, biotransformed and transferred in aquatic ecosystems are relatively unknown. Examination of whole marine ecosystems rather than individual organisms provides greater insights into the biogeochemical cycling of arsenic. Rocky intertidal zones, which have a high abundance of organisms but low ecological diversity, are an important marine habitat. This study examines the cycling of arsenic within intertidal ecosystems to further understand its distribution and transfer.
Abstract. The present study reports total arsenic and arsenic species in a short rocky intertidal marine food chain in NSW, Australia. Total mean arsenic concentrations increased up the food chain in the following order: 4 ± 2 µg g–1 in attached rock microalgae, 31 ± 14 µg g–1 in Bembicium nanum Lamarck, 45 ± 14 µg g–1 in Cellana tramoserica Sowerby, 58 ± 14 µg g–1 in Nerita atramentosa Reeve, 75 ± 15 µg g–1 in Austrocochlea constrica Lamarck (a herbivore) and 476 ± 285 µg g–1 in the carnivore Morula marginalba Blainville. Significant differences in arsenic concentrations of B. nanum, N. atramentosa and M. marginalba were found among locations and may be related to food availability, spawning or differences in age and/or size classes of individuals. Significant differences in arsenic concentrations were also found within locations among species, and increased in the order: rock microalgae < B. nanum < C. tramoserica < N. atramentosa < A. constricta < M. marginalba. Although small differences in total arsenic concentrations were found among locations for some gastropod species, arsenic species proportions were very consistent within gastropod species across locations. The majority of arsenic in Homosira banksii (macroalgae) was oxo-arsenoribosides, with thio-arsenoribosides making up ~10% of the total methanol–water extractable arsenic. The rock microalgae contained arsenobetaine (AB) (59 ± 5%) and arsenoribosides (36 ± 15%). The AB content of the herbivores B. nanum, N. atramentosa and A. constricta ranged from 71 to 95%, and that of the carnivore M. marginalba was 98%. Most gastropods contained thio-arsenosugars (up to 13 ± 3% of total extractable arsenic), with C. tramoserica containing higher proportions of thio-phosphate arsenoriboside (7 ± 2%) and lower proportions of AB (69 ± 4%). Glycerol trimethylarsonioribosides (1.4 ± 0.1%) were also found in most of the herbivorous gastropods. Oxo-dimethylarsinoylethanol (oxo-DMAE) was found in N. atramentosa (<1%).
Stable Carbon Isotope Analysis of Anthropogenic Volatile Halogenated C1 and C2 Organic Compounds
Authors: Auer Nicole R. , Schulz-Bull Detlef E.
Published: September 2006

Environmental Context.Volatile halogenated organic compounds (VHOCs), ubiquitous trace gases of natural or man-made origin, have gained increasing attention due to their adverse health effects on humans and wildlife, and their potential for catalytic ozone destruction. However, it is difficult to confront VHOC emission budgets as the processes responsible for the formation and degradation of these compounds are complex, and their emission and persistence are affected by variations in the environment and climate. In order to understand VHOCs and reduce their environmental impact, it is necessary to study the isotopic composition of VHOCs produced by different sources, in addition to their concentrations and fluxes in the environment. In this paper, the determination of the carbon isotope range of VHOCs produced by human activities adds useful basic information for future studies of their environmental fate.

Abstract. This paper presents the C13/C12 determination of 27 industrial volatile halogenated organic compounds (VHOCs) from different suppliers via gas chromatography combustion isotope-ratio mass spectrometry (GC-C-IRMS). A total of 60 samples, containing one or two carbon atoms, plus chlorine, bromine and iodine substituents, were analyzed to provide a basis for their further comparison with naturally produced VHOC δ13C values. The results indicate a wide range in the carbon isotope signature (–62‰ and –5‰). For chloroiodomethane alone, positive carbon isotope values of 33‰ (Fluka) and 59‰ (VWR International) were found. Each C1 and C2 compound has a distinctive carbon isotope composition, depending on the individual manufacturing reactions, the use of different carbon sources, differences in the composition of the same type of raw material and/or conditions during the manufacturing process. The last two factors are probably responsible for the δ13C discrepancies of ~5‰ found between manufacturers of the same compound. Larger deviations are mainly associated with different carbon isotope signatures of the reactant. Therefore, it is suggested that the reporting of a stable carbon isotope ratio for an anthropogenic VHOC include details of the manufacturing process or alternatively the supplier.
Gaseous and Particulate Products from the Atmospheric Ozonolysis of a Biogenic Hydrocarbon, Sabinene
Authors: Chiappini Laura , Carrasco Nathalie , Temine Brice , Picquet-Varrault Benedicte , Durand-Jolibois Régine , Wenger John C. , Doussin Jean-François
Published: September 2006

Environmental Context. Volatile organic compounds (VOCs) are a source of ozone and secondary organic aerosols, which have significant effects in the lower troposphere and on human health. The emission rate of VOCs from plants exceeds anthropogenic emissions by a factor of ten. In order to understand how these plant-derived compounds influence global ozone budgets, studies into the atmospheric reactions of these compounds are needed. This study investigates the ozonolysis of sabinene, a VOC abundantly emitted by trees in Europe.
Abstract. This work investigates both the gaseous and particulate phase products from the ozonolysis of sabinene in smog chamber experiments. The gaseous phase was analyzed in situ by FTIR. The particulate phase was analyzed after sampling with a supercritical fluid extraction technique directly coupled to gas chromatography and mass spectrometry (SFE-GC-MS) and to an in situ derivatization method. Sabinaketone, formaldehyde, and formic acid have been detected in the gaseous phase. More than 30 products have been observed in the secondary organic aerosol formed from sabinene oxidation and among them 10 have been identified as compounds containing carbonyl, hydroxyl and carboxyl groups. Hypotheses concerning reaction formation pathways have been proposed for each identified product in gaseous and particulate phases.
Feature-selective attention enhances color signals in early visual areas of the human brain
Authors: Müller M. M. , Andersen S. , Trujillo N. J. , Valdés-Sosa P. , Malinowski P. , Hillyard S. A.
Published: September 2006

We used an electrophysiological measure of selective stimulus processing (the steady-state visual evoked potential, SSVEP) to investigate feature-specific attention to color cues. Subjects viewed a display consisting of spatially intermingled red and blue dots that continually shifted their positions at random. The red and blue dots flickered at different frequencies and thereby elicited distinguishable SSVEP signals in the visual cortex. Paying attention selectively to either the red or blue dot population produced an enhanced amplitude of its frequency-tagged SSVEP, which was localized by source modeling to early levels of the visual cortex. A control experiment showed that this selection was based on color rather than flicker frequency cues. This signal amplification of attended color items provides an empirical basis for the rapid identification of feature conjunctions during visual search, as proposed by “guided search” models.
Presbycusis: A Human Temporal Bone Study of Individuals With Downward Sloping Audiometric Patterns of Hearing Loss and Review of the Literature
Authors: Nelson Erik G. , Hinojosa Raul
Published: September 2006

Objective: The purpose of this retrospective case review was to identify patterns of cochlear element degeneration in individuals with presbycusis exhibiting downward sloping audiometric patterns of hearing loss and to correlate these findings with those reported in the literature to clarify conflicting concepts regarding the association between hearing loss and morphologic abnormalities.

Methods: Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for downward‐sloping audiometric thresholds. Twenty‐one temporal bones that met these criteria were identified and compared with 10 temporal bones from individuals with normal hearing. The stria vascularis volumes, spiral ganglion cell populations, inner hair cells, and outer hair cells were quantitatively evaluated. The relationship between the severity of hearing loss and the degeneration of cochlear elements was analyzed using univariate linear regression models.

Results: Outer hair cell loss and ganglion cell loss was observed in all individuals with presbycusis. Inner hair cell loss was observed in 18 of the 21 individuals with presbycusis and stria vascularis loss was observed in 10 of the 21 individuals with presbycusis. The extent of degeneration of all four of the cochlear elements evaluated was highly associated with the severity of hearing loss based on audiometric thresholds at 8,000 Hz and the pure‐tone average at 500, 1,000, and 2,000 Hz. The extent of ganglion cell degeneration was associated with the slope of the audiogram.

Conclusions: Individuals with downward‐sloping audiometric patterns of presbycusis exhibit degeneration of the stria vascularis, spiral ganglion cells, inner hair cells, and outer hair cells that is associated with the severity of hearing loss. This association has not been previously reported in studies that did not use quantitative methodologies for evaluating the cochlear elements and strict audiometric criteria for selecting cases.
Laryngeal Cancer in the United States: Changes in Demographics, Patterns of Care, and Survival
Authors: Hoffman Henry T. , Porter Kimberly , Karnell Lucy H. , Cooper Jay S. , Weber Randall S. , Langer Corey J. , Ang Kie‐Kian , Gay Greer , Stewart Andrew , Robinson Robert A.
Published: September 2006

Background: Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer.

Objective: The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival.

Study Design: The authors conducted a retrospective, longitudinal study of laryngeal cancer cases.

Methods: Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications.

Results: This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid‐1980s to mid‐1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5‐year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced‐stage glottic cancer, early‐stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5‐year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5‐year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation.

Conclusions: The decreased survival recorded for patients with laryngeal cancer in the mid‐1990s may be related to changes in patterns of management. Future studies are warranted to further evaluate these associations.
Gastrointestinal Tract as a Target Organ for Orally Administered Insulin
Authors: Shehadeh Naim , Sukhotnik Igor , Shamir Raanan
Published: September 2006

The intestine is not considered to be a classic target tissue for insulin. Recent in vitro and in vivo experiments suggest that intestinal as well as systemic effects are observed following oral administration of insulin. Local effects include enhancement of intestinal growth, cell maturation, enzyme expression, gut adaptation after intestinal resection and reduction of intestinal permeability. Systemic effects, at least in animal models, include favorable effects on blood glucose and lipid profile and on the prevention of autoimmunity and attenuating the atherosclerosic process.
Breast‐feeding in Athens, Greece
Authors: Theofilogiannakou Melina , Skouroliakou Maria , Gounaris Antonis , Panagiotakos Demosthenis , Markantonis Sophia L.
Published: September 2006

Objectives:

To determine the prevalence, examine the influence of hospital practices and investigate potential determinants of breast‐feeding in Athens.

Patients and Methods:

Three hundred twelve mothers provided information regarding feeding practices at certain maternity hospitals in Athens, at 40 days and 6 months postpartum. Multiple logistic regression analysis was performed to evaluate the association between the initiation and maintenance of breast‐feeding and potential risk factors.

Results:

Although almost 90% of newborn infants were given a breast milk substitute one or more times during the first 2 days at the maternity hospital, the exclusive breast‐feeding percentage on the last day of hospital stay reached 85%. Breast‐feeding and exclusive breast‐feeding percentages dropped to 55% and 35%, respectively, at 40 days postpartum and to 16% and 12%, respectively, at 6 months postpartum. While in the hospital, 3% of mothers initiated breast‐feeding within 1 hour of labor, only 34% were informed about the advantages of breast‐feeding by health professionals and 42% were trained to breast‐feed by the midwives. “Rooming‐in” was not practiced in the private hospitals. The educational level was positively associated with the initiation of breast‐feeding [odds ratio (OR):1.36, confidence interval (CI):1.02‐1.81], the mother's body mass index was negatively associated with the maintenance of breast‐feeding for 40 days (OR:0.56, CI:0.32‐0.98) and 6 months (OR:0.28, CI:0.06‐1.26) and a caesarean section was negatively associated with the initiation (OR:0.24, CI:0.11‐0.49) and maintenance of breast‐feeding (OR:0.42, CI:0.20‐0.89).

Conclusions:

Breast‐feeding is not appropriately supported in certain maternity hospitals in Athens, and this is probably the cause of observed low breast‐feeding prevalence.
Abnormal Fatty Acid Pattern in Intestinal Mucosa of Children With Celiac Disease Is Not Reflected in Serum Phospholipids
Authors: Steel Daniella M. , Ryd Walter , Ascher Henry , Strandvik Birgitta
Published: September 2006

Objective:

Celiac disease (CD) is characterized by chronic inflammation of the small intestinal mucosa with disturbed epithelial transport. The fatty acid (FA) composition of intestinal membranes is important for epithelial function, and disturbances may contribute to the pathophysiology of the disease. We aimed to evaluate whether the intestinal mucosal FA status was reflected in serum phospholipids of patients with CD.

Patients and Methods:

Samples were obtained from 7 pediatric patients with active CD showing mucosal atrophy, 6 pediatric patients with CD in remission, and 11 control pediatric patients with morphologically healthy intestinal mucosa. Small intestinal biopsies were obtained using a Watson biopsy capsule under fluoroscopic control. Blood samples were collected on the same morning after an overnight fast. Tissue phospholipids were isolated by high‐performance liquid chromatography, and FAs were analyzed by capillary gas‐liquid chromatography.

Results:

Serum phospholipid FA showed marginal differences between the patients with CD and the controls. Significant differences were observed in mucosa with active CD compared with controls. Linoleic acid (18:2n‐6) level was decreased, whereas those of its derivatives were elevated, indicating increased transformation of n‐6 FA. Mead acid (20:3n‐9) level was increased, with an increased ratio of Mead acid to arachidonic acid (20:4n‐6) levels, suggesting essential fatty acid deficiency. The n‐3 FA levels were not significantly changed. During remission, the FA pattern of the intestinal mucosa was mainly similar to that in controls.

Conclusions:

The FA abnormality of intestinal mucosa in patients with active CD was not reflected in serum values. Altered FA content may contribute to the pathophysiology of the disease because FAs are important for enzymes and for the transport and receptor functions of epithelial membranes.
Oligosaccharides in Colostrum of Italian and Burkinabe Women
Authors: Musumeci Maria , Simpore Jacques , D'Agata Alfonsina , Sotgiu Stefano , Musumeci Salvatore
Published: September 2006

Human milk contains a large number of compounds to provide nutrition and defense for the newborn. Among these, oligosaccharides are present in concentrations up to 12 g/L, and their composition varies during lactation. Colostrum from 53 Burkinabe women were collected at the maternity department of St Camille Medical Centre in Ouagadougou (Burkina Faso, West Africa). Colostrum from 50 Italian women were collected at the maternity department of St Bambino Hospital in Catania (Catania, East Sicily, Italy). All mothers spontaneously delivered at term. Italian mothers received an injection of the ergot derivative ergotamine after delivery. Ergotamine, notoriously, delays breastfeeding initiation up to 2 to 3 days. Chromatographic separation of colostrum from both Burkinabe and Italian women showed a progressive appearance of oligosaccharides in the first 3 days. Burkinabe women showed high concentrations of 2‐fucosyllactose and lower concentrations of lacto‐N‐fucopentaose I. By contrast, Italian women showed inverted behaviour. A comparable percentage of the secretor genotype for the Lewis blood group phenotype in both Burkinabe and Italian women was found. According to the different ethnicity, different milk oligosaccharide profiles were documented in the present study. 2‐Fucosyllactose in milk should be biologically significant for Burkinabe infants because of the high levels found in their mothers' colostrum after the second day of lactation.
Evolution of Thiopurine Use in Pediatric Inflammatory Bowel Disease in an Academic Center
Authors: Banerjee Sanjoy , Bishop Warren P.
Published: September 2006

Objectives:

We evaluated how our use of thiopurines was altered by determination of thiopurine methyltransferase (TPMT) level and drug dose adjustment guided by a 6‐mercaptopurine metabolite assay. We further examined whether these resulted in better selection of the drug dose, improved control of disease, and decreased corticosteroid use in pediatric inflammatory bowel disease (IBD).

Patients and Methods:

This is a retrospective review of 101 pediatric patients with IBD receiving a stable dose of azathioprine (AZA) for 4 months or longer. The study group (n = 64) consisted of patients who received AZA and had metabolite levels measured. The comparison group (n = 37) consisted of patients who were receiving AZA before the availability of metabolite measurement. The TPMT level was measured in study group patients before starting AZA.

Results:

Patients with normal TPMT level received a higher starting dose of AZA than in patients who were heterozygous for TPMT deficiency (1.7 vs 0.9 mg/[kg·d], P < 0.0001). Study group patients received a higher starting dose (1.6 vs 1.2 mg/[kg·d], P = 0.001) and a higher final dose of AZA (2.4 vs 1.7 mg/[kg·d], P < 0.0001) compared with patients in the comparison group. These patients also had more dose adjustments (0.8 vs 0.4 mg/kg, P < 0.002). The number of disease exacerbations per patient per year was 55% less in the study group (95% CI, 17%‐76%, P < 0.0001). The study group patients received less prednisone (P < 0.0001) and had lower disease activity scores (P < 0.05). There was no difference between groups in infliximab use or surgery rate.

Conclusions:

Azathioprine dose adjustment using a 6‐mercaptopurine metabolite assay was associated with use of higher doses, improved control of disease and decreased corticosteroid use in pediatric patients with IBD.
Evaluation of a Urine‐based Enzyme‐linked Immunosorbent Assay Test for the Detection of Helicobacter pylori Infection Among 3‐ to 5‐Year‐Old Israeli Arab Healthy Children
Authors: Muhsen Khitam , Athamna Abed , Athamna Muhammad , Spungin‐Bialik Anya , Cohen Dani
Published: September 2006

We conducted a community‐based study among 159 healthy Israeli Arab children aged 3 to 5 years old to examine the validity of the HpELISA kit (URINELISA, Otuska Phamaceuticals Co, Ltd, Tokyo, Japan) for detection Helicobacter pylori IgG antibodies in urine. The polyclonal H. pylori stool antigen test (Premier HpSA) served as the gold standard. The sensitivity, specificity, positive and negative predictive values of the URINELISA kit were 34.2%, 96.3%, 90% and 60%, respectively. Using a cutoff value calculated based on the receiver operating characteristic curve (0.066), the corresponding figures were 65.8%, 87.5%, 83% and 72%, respectively. These data indicate that the usefulness of the URINELISA test in epidemiological studies in healthy young children is limited.
Analysis of CFTR, SPINK1, PRSS1 and AAT Mutations in Children With Acute or Chronic Pancreatitis
Authors: Sobczyńska‐Tomaszewska Agnieszka , Bąk Daniel , Oralewska Beata , Oracz Grzegorz , Norek Aleksandra , Czerska Kamila , Mazurczak Tadeusz , Teisseyre Mikołaj , Socha Jerzy , Zagulski Marek , Bal Jerzy
Published: September 2006

Objectives:

Defects of PRSS1, SPINK1, CFTR and AAT are considered causative or predisposing to pancreatitis. The aim of this study was to evaluate the impact of these defects into molecular pathology of chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP).

Methods:

Ninety‐two children with CP or ARP, 55 family members and 50 controls were investigated. The subjects were screened for PRSS1 mutations: R122H, R122C, A16V, N29I; SPINK1 N34S variant; panel of 14 CFTR defects: INNOLiPA CFTR12, CFTRdele2,3 and IVS8‐T variant or panel of 3 CFTR defects‐F508del, CFTRdele2,3 and IVS8‐T; AAT mutations: E264V, E342K.

Results:

We identified 1 mutated allele in at least 1 of 4 genes in 31 of 92 patients and 12 of 50 controls (P = 0.157). Mutations in SPINK1 and PRSS1 were most frequent. PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34S SPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768). The frequency of mutations in CFTR alleles was similar to controls (4.9% vs 5%, P = 0.587). Overall frequency of AAT mutations was lower than in the controls. Family studies showed that defects in the examined genes did not always segregate with disease.

Conclusions:

PRSS1 defects seem to be causative for pancreatitis, whereas defects in SPINK1 are suggested to be associated with the disease. No association between CFTR mutations and pancreatitis was observed. The importance of AAT variants remains speculative.
Agroinfection‐based high‐throughput screening reveals specific recognition of INF elicitins in Solanum
Authors: VLEESHOUWERS VIVIANNE G. A. A. , DRIESPRONG JAN‐DAVID , KAMPHUIS LARS G. , TORTO‐ALALIBO TRUDY , VAN'T SLOT KLAAS A. E. , GOVERS FRANCINE , VISSER RICHARD G. F. , JACOBSEN EVERT , KAMOUN SOPHIEN
Published: September 2006

We adapted and optimized the use of the Agrobacterium tumefaciens binary PVX expression system (PVX agroinfection) to screen Solanum plants for response to pathogen elicitors and applied the assay to identify a total of 11 clones of Solanum huancabambense and Solanum microdontum, out of 31 species tested, that respond to the elicitins INF1, INF2A and INF2B of Phytophthora infestans. Prior to this study, response to INF elicitins was only known in Nicotiana spp. within the Solanaceae. The identified S. huancabambense and S. microdontum clones also exhibited hypersensitivity‐like cell death following infiltration with purified recombinant INF1, INF2A and INF2B, thereby validating the screening protocol. Comparison of INF elicitin activity revealed that Nicotiana plants responded to significantly lower concentrations than Solanum, suggesting variable levels of sensitivity to INF elicitins. We exploited natural variation in response to INF elicitins in the identified Solanum accessions to evaluate the relationship between INF recognition and late blight resistance. Interestingly, several INF‐responsive Solanum plants were susceptible to P. infestans. Also, an S. microdontum ×Solanum tuberosum (potato) population that segregates for INF response was generated but failed to identify a measurable contribution of INF response to resistance. These results suggest that in Solanum, INF elicitins are recognized as general elicitors and do not have a measurable contribution to disease resistance.
Modern diagnosis and management of the porphyrias
Authors: Sassa Shigeru
Published: September 2006

Recent advances in the molecular understanding of the porphyrias now offer specific diagnosis and precise definition of the types of genetic mutations involved in the disease. Molecular diagnostic testing is powerful and very useful in kindred evaluation and genetic counselling when a disease‐responsible mutation has been identified in the family. It is also the only way to properly screen asymptomatic gene carriers, facilitating correct treatment and appropriate genetic counselling of family members at risk. However, it should be noted that DNA‐based testing is for the diagnosis of the gene carrier status, but not for the diagnosis of clinical syndrome or severity of the disease, e.g. an acute attack. For the diagnosis of clinically expressed porphyrias, a logical stepwise approach including the analysis of porphyrins and their precursors should not be underestimated, as it is still very useful, and is often the best from the cost‐effective point of view.
Gö6976 is a potent inhibitor of the JAK 2 and FLT3 tyrosine kinases with significant activity in primary acute myeloid leukaemia cells
Authors: Grandage Victoria L. , Everington Tamara , Linch David C. , Khwaja Asim
Published: September 2006

Aberrant activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling is implicated in a number of haematological malignancies and effective JAK inhibitors may be therapeutically useful. We found that Gö6976, an indolocarbazole inhibitor of the calcium‐dependent isozymes of protein kinase C (PKC), inhibited interleukin 3/granulocyte‐macrophage colony‐stimulating factor‐induced signalling, proliferation and survival whereas Gö6983, a broad spectrum PKC inhibitor, had no such effects. Gö6976 was found to be a direct and potent inhibitor of JAK2 in vitro. Gö6976 also inhibited signalling, survival and proliferation in cells expressing the leukaemia‐associated TEL–JAK2 fusion protein and the myeloproliferative disorder (MPD)‐associated JAK2 V617F mutant. In primary acute myeloid leukaemia (AML) cells, incubation with Gö6976 reduced constitutive STAT activity in all cases studied. In addition, Akt and mitogen‐activated protein kinase phosphorylation were reduced in 4/5 FLT3‐internal tandem duplication (ITD) positive AML cases and 7/13 FLT3‐wild‐type (WT) cases. Expression of FLT3‐WT, ITD and D835Y in 32D cells showed that Gö6976 is also a potent inhibitor of WT and mutant FLT3. In AML cells, Gö6976 reduced the survival to 55 ± 5% of control in FLT3‐ITD cases and to 69 ± 5% in FLT3‐WT samples. These data may help identify clinically useful compounds based on the structure of Gö6976, which can be employed for the treatment of MPDs as well as AML.
An amplified sandwich EIA for the measurement of soy aeroallergens
Authors: Gómez‐Ollés S. , Cruz M. J. , Renström A. , Doekes G. , Morell F. , Rodrigo M. J.
Published: September 2006

Background
Soy hull low‐molecular‐weight (SHLMW) allergens were responsible for the soy asthma epidemics in Barcelona, with one 7.5 kDa protein (Gly m 1) being the main IgE‐binding component. The aims of this study were to develop a sensitive sandwich enzyme immunoassay (EIA) using rabbit polyclonal antibodies to measure low levels of SHLMW allergens, and to compare this method with the previously described human IgE EIA‐inhibition technique.

Methods
IgG was isolated from serum of rabbits immunized with a chromatographically purified SHLMW extract (SHLMWE). Antibody‐binding profiles were compared with those of human IgE anti‐soy protein antibodies by Western blot analysis. An amplified sandwich EIA was developed using the purified SHLMWE as a calibration standard. Results were expressed in nanograms per millilitre. To compare the two assays, 54 air samples were analysed by both methods.

Results
SDS‐PAGE of the SHLMWE revealed four bands of 6, 8, 15 and 17 kDa. Gly m 1 in the SHLMWE was identified by fingerprinting. The detection limit of the assay was 40 pg/mL. The two methods correlated well (r=0.89; P<0.001). The allergen concentration was detected in all 54 (100%) samples by the sandwich EIA but in only 37 (68.5%) by the EIA inhibition.

Conclusions
The amplified sandwich EIA for SHLMW components has a high sensitivity and appeared to be a useful tool for the measurement of airborne SHLMW allergens, even at relatively low concentrations. Moreover, the method uses rabbit antibodies at high dilutions and does not require human sera, with limited availability and quantitative and qualitative pool‐to‐pool variability.
Role of interleukin‐17F in chronic inflammatory and allergic lung disease
Authors: Hizawa N. , Kawaguchi M. , Huang S.‐K. , Nishimura M.
Published: September 2006

IL‐17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro‐inflammatory and neutrophil‐mobilizing cytokines. The importance of the IL‐17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL‐17F is a recently discovered member of the IL‐17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL‐17A, the founding member of the IL‐17 family, and IL‐17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL‐17A or IL‐17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case–control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild‐type IL‐17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL‐17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL‐17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures.
Association between air pollution and asthma admission among children in Hong Kong
Authors: Lee S. L. , Wong W. H. S. , Lau Y. L.
Published: September 2006

Objective
To examine the association of air pollutants with hospital admission for childhood asthma in Hong Kong.

Methods
Data on hospital admissions for asthma, influenza and total hospital admissions in children aged 18 years at all Hospital Authority hospitals during 1997–2002 were obtained. Data on daily mean concentrations of particles with aerodynamic diameter <10 μm (i. e. PM10) and <2.5 μm (i. e. PM2.5), nitrogen dioxide (NO2), sulphur dioxide (SO2), and ozone (O3) and data on meteorological variables were associated with asthma hospital admissions using Poisson's regression with generalized additive models for correction of yearly trend, temperature, humidity, day‐of‐week effect, holiday, influenza admissions and total hospital admission. The possibility of a lag effect of each pollutant and the interaction of different pollutants were also examined.

Results
The association between asthma admission with change of NO2, PM10, PM2.5 and O3 levels remained significant after adjustment for multi‐pollutants effect and confounding variables, with increase in asthma admission rate of 5.64% (3.21–8.14) at lag 3 for NO2, 3.67% (1.52–5.86) at lag 4 for PM10, 3.24% (0.93–5.60) at lag 4 for PM2.5 and 2.63% (0.64–4.67) at lag 2 for O3. Effect of SO2 was lost after adjustment.

Conclusion
Ambient levels of PM10, PM2.5, NO2 and O3 are associated with childhood asthma hospital admission in Hong Kong.
Contact with livestock – a protective effect against allergies and asthma?
Authors: Dimich‐Ward H. , Chow Y. , Chung J. , Trask C.
Published: September 2006

Background
A ‘protective farm factor’ possibly related to livestock exposure is hypothesized to reduce the risk for allergic sensitization.

Objective
The purpose of this study was to determine whether 4‐H club youth, who have opportunities for contact with livestock through club activities, have reduced risks of respiratory and allergic symptoms according to residence on a farm or exposure to livestock.

Methods
A cross‐sectional postal survey was completed by British Columbia 4‐H members 8–20 years of age; a subset underwent skin prick testing as well. The association of farm residence and livestock exposure variables with symptoms were evaluated using logistic regression with adjustment for age, sex, cat and/or dog ownership, parental history of allergic disease, parental education, number of older siblings and exposure to smokers at home.

Results
Questionnaires were completed by 1158 participants (response rate 50.3%); of these, a subset of 317 had skin prick tests (SPTs) (response rate 64.4%). Current residence on a farm was associated with a lower prevalence of ever having wheeze and asthma, as well as symptoms of atopic dermatitis. Variables relating to residence in a farm or rural area with livestock were more strongly associated with respiratory and allergic symptoms than were the livestock exposure variables such as frequency of contact and hours of barn use. The adjusted odds ratios for living in a farm residence in comparison with a rural non‐livestock area were 0.49 (95% confidence interval (CI) 0.27–0.89) for diagnosed asthma, 0.51 (95% CI 0.30–0.85) for allergic rhinitis and 0.45 (95% CI 0.24–0.84) for atopic dermatitis.

Conclusion
Our findings suggest that some aspects of the farm environment, not just attributable to contact with livestock, were protective for respiratory and allergic conditions among 4‐H youth.
Killed Mycobacterium vaccae suspension in children with moderate‐to‐severe atopic dermatitis: a randomized, double‐blind, placebo‐controlled trial
Authors: Berth‐Jones J. , Arkwright P. D. , Marasovic D. , Savani N. , Aldridge C. R. , Leech S. N. , Morgan C. , Clark S. M. , Ogilvie S. , Chopra S. , Harper J. I. , Smith C. H. , Rook G. A. W. , Friedmann P.S.
Published: September 2006

Background
The hygiene hypothesis is often proposed to explain the high prevalence of atopy in the western world. Dysregulation of the immune system may result from inadequate exposure to micro‐organisms such as mycobacteria. A small trial suggested that a killed extract of Mycobacterium vaccae ameliorates atopic dermatitis (AD).

Objectives
To confirm in a large clinical trial whether killed M. vaccae ameliorates AD in 5–16‐year‐old children.

Methods
This was a randomized, placebo‐controlled, double‐blind, multi‐centre study of the effect of intradermal injection of killed M. vaccae (0.1 or 1 mg) on patients, aged 5–16, with moderate‐to‐severe AD. Patients were followed up for 24 weeks. The primary end point was the change in severity of AD at 12 weeks, assessed using the six area, six‐sign, atopic dermatitis (SASSAD) score. Secondary end points included changes in disease extent, patient's global assessment and children's dermatology life quality index.

Results
There were 166 patients randomized. The mean SASSAD score fell to a similar degree at week 12 in all treatment arms: from 33 to 24, (26%) in the high‐dose group, from 30 to 23 (25%) in the low‐dose group and from 36 to 27 (24%) in the placebo group (P>0.05). Secondary end points followed the same trend. Adverse events were generally those expected to occur in this population. Injection site reactions occurred in 32 patients at week 4.

Conclusions
M. vaccae was no more effective than the placebo in ameliorating the severity of AD.
Most of diaplacentally transferred allergen is retained in the placenta
Authors: Szépfalusi Z. , Loibichler C. , Hänel‐Dekan S. , Dehlink E. , Gerstmayr M. , Pichler J. , Eiwegger T. , Horvat R. , Urbanek R.
Published: September 2006

Background
Transplacental transfer of nutritive and inhalant allergens has been described being potentially responsible for a series of events leading to antigen‐specific immune responses in the fetus. As such, cord blood T cell responses appear ubiquitously. However, studies failed to reveal a consistent dose–response relationship between antenatal allergen exposure and allergen‐specific cellular reactivity in cord blood.

Objective
To examine the transfer process of allergens (ovalbumin (OVA), β‐lactoglobulin (BLG), birch pollen allergen Bet v1) in placental tissue (BeWo cell line, ex vivo placenta model).

Methods
The choriocarcinoma cell line BeWo was used to study the allergen uptake and transfer experiments in vitro. In the ex vivo placenta model the contribution of different placental compartments was evaluated. For this, immuno‐histochemistry, immuno‐electronmicroscopy and ELISA techniques were applied using monoclonal antibodies to Bet v1, OVA and ‐BLG.

Results
In vitro transfer studies on a BeWo cell‐layer revealed an intracellular allergen uptake and a trans‐trophoblastic allergen transfer, which was temperature‐ and concentration dependent, pH sensitive and asymmetric. Allergen‐specific staining of placental tissue after allergen perfusion (BLG) demonstrated bulk of the allergen in the syncytio‐trophoblastic cell layer and minor staining in the villous stroma and in the endothelium of fetal vessels. Immunogold staining revealed an accumulation of the perfused allergen in the trophoblastic basement membrane.

Conclusion
In vitro/ex vivo trans‐trophoblastic and trans‐placental allergen transfer is shown with an accumulation of most of the allergen in placental tissues, potentially explaining the missing direct dose–response relationship between prenatal (maternal) allergen exposure and allergen‐specific cellular reactivity in cord blood.
Expression of T cell receptor variable region families by bone marrowγδT cells in patients with IgA nephropathy
Authors: BUCK K S , FOSTER E M , WATSON D , BARRATT J , PAWLUCZYK I Z A , KNIGHT J F , FEEHALLY J , ALLEN A C
Published: September 2006

IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA (pIgA). Abnormalities of the IgA system include reduced mucosal and increased bone marrow (BM) pIgA production. γδ T cells are regulators of mucosal IgA production and oral tolerance. We have described previously a deficiency of γδ T cells expressing Vγ3 and Vδ3 from the duodenal mucosa in IgAN. Since pIgA production is displaced to the BM, we have now studied BM γδ T cells in IgAN.

Peripheral blood and BM aspirates were obtained from 14 patients with IgAN and 15 controls. Expression of TCR γ and δ V region families was analysed by semiquantitative RT-PCR, and CDR3 spectratyping of Vγ1–4 and Vδ3 genes was performed. We found no difference between IgAN and controls in the V region usage of blood γδ T cells. However, in the BM of patients with IgAN, there was significantly reduced expression of the V region families Vγ3 and Vδ3, with the decrease in Vδ3 being particularly striking. CDR3 spectratyping showed no abnormalities in blood or BM samples. Vγ3 and Vδ3 are underexpressed in the duodenum and the BM in IgAN. The combination of imbalanced mucosal and systemic pIgA production with deficient expression of γδ T cells using Vγ3 and Vδ3 in both sites may imply a role for these γδ T cells in the normal regulation of IgA immune responses, and in the complex immunopathogenesis of IgAN.
Detection of BRAFV600E mutation on fine needle aspiration specimens of thyroid nodule refines cyto‐pathology diagnosis, especially in BRAFV600E mutation‐prevalent area
Authors: Chung Ki‐wook , Yang Sun Kyung , Lee Geon Kook , Kim Eun Young , Kwon Soim , Lee Sang Hyun , Park Do Joon , Lee Hyun Sook , Cho Bo Youn , Lee Eun Sook , Kim Sun Wook
Published: September 2006

Background  Between 10 and 30% of the fine needle aspiration biopsies (FNABs) of thyroid nodules are diagnosed as ‘indeterminate’. A molecular diagnostic method is needed to reduce unnecessary surgery in this group. In Korea, most thyroid cancer is the classic papillary type and the BRAFV600E mutation is highly prevalent.

Aim  To evaluate the role of pre‐operative detection of BRAFV600E mutation in the FNAB specimens of thyroid nodules in a BRAFV600E mutation‐prevalent geographical area.

Patients and methods  In 137 specimens of FNAB (107 papillary thyroid carcinomas (PTC); 3 follicular thyroid carcinomas (FTC); 2 undifferentiated thyroid carcinomas; 25 benign lesions), both direct DNA sequencing and PCR‐RFLP were used for detecting the BRAFV600E mutation. The sensitivity and specificity were calculated. We analysed the association between BRAFV600E mutation and the clinico‐pathological parameters.

Results  The BRAFV600E mutation was present in 93 (83%) of 112 thyroid cancers. Direct DNA sequencing showed a sensitivity of 83·0% and a specificity of 96·0%. The sensitivity and specificity of PCR‐RFLP were 78·6% and 80·0%, respectively. Among 25 cases with indeterminate FNAB cytology, 8 patients had malignant lesions (5 PTC and 3 FTC). Three (60%) of 5 PTCs and 1 out of 17 benign lesions had BRAFV600E mutation (only one false positive case and the definitive pathology showed atypical nodular hyperplasia that could be a premalignant lesion). The diagnostic accuracy of this molecular method in only the 25 indeterminate nodules was 76% (19/25). No mutation was found in 3 FTCs. Among 107 PTCs, there was no significant association of the BRAFV600E mutation with the known risk factors.

Conclusion  Detection of the BRAFV600E mutation in FNAB specimens refines the FNAB‐cytology diagnosis, especially in a BRAFV600E mutation‐prevalent area. Direct DNA sequencing was a more reliable method than PCR‐RFLP for detecting the BRAFV600E mutation with a high sensitivity and specificity.
Glucose tolerance and lipid profile in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomised controlled trial
Authors: Heemstra K. A. , Smit J. W. A. , Eustatia‐Rutten C. F. A. , Heijboer A. C. , Frölich M. , Romijn J. A. , Corssmit E. P. M.
Published: September 2006

Objective  The impact of prolonged subclinical hyperthyroidism on glucose and lipid metabolism is unclear. Therefore, we evaluated glucose and lipid metabolism in patients with differentiated thyroid carcinoma (DTC) on TSH suppressive thyroxine therapy as a model for subclinical hyperthyroidism and investigated whether restoration to euthyroidism affects metabolism.

Design  We performed a prospective, single‐blinded, placebo‐controlled, randomised trial of 6 months duration with 2 parallel groups.

Patients  Twenty‐five subjects with a history of differentiated thyroid carcinoma with > 10 years TSH‐suppressive therapy with l‐thyroxine completed the study. l‐thyroxine dose was replaced by study medication containing l‐thyroxine or l‐thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low‐TSH group, 13 patients) and euthyroidism (euthyroidism group, 12 patients).

Measurements  We evaluated glucose metabolism by glucose tolerance test and HOMA (IR) and lipid metabolism by lipid profile. In addition, we measured plasma concentrations of glucoregulatory hormones.

Results  At baseline, glucose tolerance, HOMA (IR), lipid profile and plasma concentrations of glucoregulatory hormones were within the normal range. No significant differences between the low TSH and euthyroidism group were observed. After 6 months, neither glucose nor lipid metabolism in the low TSH group were different from baseline values.

Conclusion In summary, glucose and lipid metabolism in patients with DTC and long‐term subclinical hyperthyroidism in general are not affected. Restoration of euthyroidism in general does not affect glucose and lipid metabolism.
Abnormal expression of PPAR gamma isoforms in the subcutaneous adipose tissue of patients with Cushing's disease
Authors: Bogazzi Fausto , Ultimieri Federica , Raggi Francesco , Russo Dania , Manetti Luca , Cosci Chiara , Sardella Chiara , Costa Aurelio , Santini Ferruccio , Locci Teresa , Bartalena Luigi , Martino Enio
Published: September 2006

Background  Obesity is a clinical feature of patients with Cushing's disease. Peroxisome proliferators‐activated receptor (PPAR)γ is the master regulator of adipogenesis; however, the expression of PPARγ isoforms in the subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown.

Aim and methods  The expression of PPARγ1 and PPARγ2 was evaluated by real‐time reverse transcription polymerase chain reaction (RT‐PCR) and immunofluorescence (PPARγ2 only) in SAT samples of 7 patients with untreated active Cushing's disease (CushingUNTR), 8 with Cushing's disease in remission (CushingREM) after pituitary adenomectomy, 15 normal lean subjects (ControlLEAN), and 15 obese patients (ControlOBE).

Results  ControlLEAN had a higher degree of PPARγ1 than PPARγ2 (PPARγ2/PPARγ1 ratio, 0·55 ± 0·35). PPARγ2/PPARγ1 ratio decreased in CushingUNTR (0·10 ± 0·043, P < 0·03 vs. ControlLEAN and ControlOBE), because of either increased PPARγ1 or reduced PPARγ2 expression. PPARγ2/PPARγ1 ratio was 0·48 ± 0·07 in CushingREM patients (P < 0·04 vs. CushingUNTR, P < 0·03 vs. ControlOBE). PPARγ2/PPARγ1 ratio was higher in ControlOBE 0·90 ± 0·38 than in ControlLEAN (P < 0·005 vs. ControlLEAN, P < 0·03 vs. CushingREM, P < 0·009 vs. CushingUNTR). PPARγ2/PPARγ1 ratio was related to serum cortisol levels only in patients with Cushing'disease (r = 0·688, P < 0·02).

Conclusions  CushingUNTR patients had an abnormal expression of PPARγ isoforms in SAT related to serum cortisol levels. Although further studies are necessary, it is conceivable that variations in the expression of PPARγ isoforms might have a role in the abnormal adipogenesis of patients with Cushing's disease.