bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: biological drugs in Crohn's disease
Authors: KAMM M. A.
Published: August 2006

Biological drugs have opened new therapeutic horizons for treating Crohn's disease (CD), but have also brought with them issues related to immunogenicity, long‐term efficacy, safety and cost.

At present, inhibitors tumour necrosis factor and adhesion molecules are the most advanced in use and development.

When treating luminal disease with infliximab, two‐thirds of patients respond initially. The ACCENT 1 study demonstrated that 28% of initial responders are in remission for 1 year. Infliximab has also had a major impact on the management of Crohn's anorectal fistulas. The ACCENT 2 study demonstrated initial response in two‐thirds of patients. One‐fifth of all treated patients were healed at 1 year. Infliximab diminished the need for further surgery.

Magnetic resonance imaging scanning allows the extent of deep healing to be assessed and may influence the duration of treatment. The Mayo Clinic experience in 500 patients demonstrated 6% serious adverse events related to infliximab. The TREAT registry will provide long‐term safety data on a larger group of patients. Concurrent immunosuppressive drugs and pre‐infusion steroids can decrease antibody formation to infliximab. Screening for tuberculosis (TB) diminishes the rate of TB activation.

Biological drugs can offer great therapeutic benefit, but their use must be considered in context.
Oral V2 receptor antagonist (RWJ‐351647) in patients with cirrhosis and ascites: a randomized, double‐blind, placebo‐controlled, single ascending dose study
Authors: THULUVATH P. J. , MAHESHWARI A. , WONG F. , YOO H. W. , SCHRIER R. W. , PARIKH C. , STEARE S. , KORULA J.
Published: August 2006

Background

RWJ‐351647 is a selective V2 receptor antagonist that inhibits vasopressin‐induced water reabsorption in the kidney.

Aim

To investigate the safety and tolerability of RWJ‐351647 compared with placebo after single oral dose administration to patients with cirrhosis and ascites, on a stable treatment with furosemide and spironolactone.

Methods

Single oral doses of 1, 2 and 5 mg of RWJ‐351647 were administered to 24 patients with ascites on stable concomitant diuretic treatment.

Results

RWJ‐351647 had a tmax of 1 to 1.1 h and mean half‐life of 10.4–17.4 h. There was no affect on the pharmacokinetics of concomitant diuretics. Increases in cumulative urine volume and free water excretion, and a decrease in urine osmolality were noted in a dose‐dependent manner reaching the statistical significance at the 5‐mg dose. Four patients exhibited a decrease of >2 kg in weight in the 24 h after dosing. RWJ‐351647 was well tolerated, with no evidence of a dose‐related increase in adverse events when compared with placebo. No changes in either serum chemistry or plasma AVP (arginine vasopressin) and renin levels were observed despite the observed aquaresis.

Conclusion

RWJ‐351647 is an effective aquaretic causing dose‐dependent increases in urine output and free water clearance, when co‐administered with conventional diuretics in patients with cirrhosis and ascites.
Alterations in peripheral blood lymphocyte cytokine expression in obesity
Authors: O'Rourke R W , Kay T , Lyle E A , Traxler S A , Deveney C W , Jobe B A , Roberts C T , Marks D , Rosenbaum J T
Published: August 2006

Obesity is characterized by alterations in immune and inflammatory function. In order to evaluate the potential role of cytokine expression by peripheral blood mononuclear cells (PBMC) in obesity-associated inflammation, we studied serum protein levels and mRNA levels in PBMC of interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α and IL-1Ra in nine lean and 10 obese subjects. Serum IL-1β was undetectable, IL-1Ra serum levels were elevated, serum levels of TNF-α were decreased and serum levels of IL-6 were similar in obese subjects compared to lean subjects, while transcript levels of IL-6, IL-1β and TNF-α, but not IL-1Ra, were decreased in PBMC from obese subjects. PBMC from obese subjects did, however, up-regulate cytokine expression in response to leptin. Thus, obesity-associated changes in IL-1Ra serum levels and IL-6 mRNA levels were not correlated with changes in cognate mRNA and serum levels, respectively, while TNF-α serum levels and PBMC mRNA levels were both decreased in obese patients. While immune alterations in obesity are manifest in peripheral blood lymphocytes, the general lack of correlation between altered serum levels and altered PBMC gene expression suggests that PBMC may not be the source of aberrant serum cytokine levels in obesity.
Coincidence of different structures of mucosa-associated lymphoid tissue (MALT) in the respiratory tract of children: no indications for enhanced mucosal immunostimulation in sudden infant death syndrome (SIDS)
Authors: Debertin A S , Tschernig T , Schürmann A , Bajanowski T , Brinkmann B , Pabst R
Published: August 2006

Mucosa-associated lymphoid tissue (MALT) is the principal inductive site for mucosal immune responses that are capable of T and B cell responses and antigen-specific responses. In previous independent studies different structures of MALT, e.g. bronchus-, larynx- and nose-associated lymphoid tissue (BALT, LALT, NALT) have been described separately in various frequencies in the human respiratory tract over life spans. Because upper respiratory tract infections are common in infants, dysregulations of mucosal immune responses might be seriously involved in the aetiology of sudden infant death syndrome (SIDS). In the present study the coincidental occurrence of the three different MALT structures in the respiratory tract within the same patients were studied, and cases of SIDS and children who had died from different traumatic and natural causes of death (non-SIDS) were compared. First, the frequency of BALT and LALT in 46 children (35 SIDS, 11 non-SIDS) with or without NALT were examined. A tendency was found of a coincidence of respiratory MALT structures. In 50 additional cases of infant death (30 SIDS, 20 non-SIDS) from the multi-centric German Study on Sudden Infant Death Syndrome (GeSID) where death had occurred in the first year of life, the coincidence was evaluated. A coincidental occurrence of BALT, LALT and NALT or BALT and LALT (each about 30%) was found in both groups, whereby the coincidence in SIDS and the control patients did not differ. Interestingly, the children with coincidental MALT were strikingly older, supporting the hypothesis of respiratory MALT formation via environmental stimulation over time.
Role of Th1-stimulating cytokines in bacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against mouse bladder cancer MBT-2 cells
Authors: Luo Y , Yamada H , Evanoff D P , Chen X
Published: August 2006

Previously, we have demonstrated that macrophages exhibited cytotoxicity toward mouse bladder cancer MBT-2 cells upon bacille Calmette–Guérin (BCG) stimulation. In this study, we have investigated the role of Th1-stimulating cytokines in BCG-induced macrophage cytotoxicity. Thioglycollate-elicited peritoneal exudate cells (PECs) were used as a conventional source for macrophages and the induction of PEC effector functions (cytolytic activity and cytokine production) by BCG was evaluated in vitro. The BCG-activated PECs showed potent cytotoxicity and killed MBT-2 cells in a dose-dependent manner. Depletion of T cells, natural killer (NK) cells, or both, in PEC preparations exhibited a marginal or small reduction of MBT-2 cell killing, suggesting that macrophages played a primary role in PEC cytotoxicity. Transwell assays indicated that the maximal PEC cytotoxicity required both direct cell–cell contact and soluble factors such as interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Neutralizing endogenous cytokines interleukin (IL)-12, IL-18, IFN-γ or TNF-α reduced PEC cytotoxicity by 38%, 22%, 15% and 94%, respectively. Supplementation of BCG with recombinant (r)IL-2, rIL-12 or rIL-18 increased PEC cytotoxicity by approximately twofold. Compared with control BCG for PEC stimulation, rBCGs expressing IL-2 or IL-18 showed enhanced MBT-2 cell killing by PECs. Increased cytokine production (IFN-γ, TNF-α and IL-6) was also observed in rBCG-stimulated PEC cultures. Taken together, these results suggest that Th1-stimulating cytokines play an important role in BCG-induced macrophage cytotoxicity and that combination of BCG with selected Th1-stimulating cytokines, either supplemented or expressed by BCG, may enhance the effect of BCG in the treatment of bladder cancer patients.
Post-translational modifications of the major linear epitope 169–190aa of Ro60 kDa autoantigen alter the autoantibody binding
Authors: Terzoglou A G , Routsias J G , Moutsopoulos H M , Tzioufas A G
Published: August 2006

Ro60 kDa is a member of the Ro/LaRNP ribonucleoprotein complex and its major linear B cell epitope, corresponding to the region 169–190aa, has been found to be the initial target of the autoimmune response in patients with systemic lupus erythematosus. This sequence contains one serine and two arginine amino acid residues, which can potentially be modified post-translationally by phosphorylation or citrullination, respectively. The aim of this study was to develop an immunoassay for anti-Ro60 kDa epitope antibody detection and to investigate the changes in the antigenicity of the Ro60 kDa epitope when it is post-translationally modified, by either citrullination or phosphorylation. Peptide analogues corresponding to the unmodified form of the epitope, its phosphorylated form, and a form with both arginine residues citrullinated were synthesized. The peptide coating conditions were investigated and it was found that the use of highly hydrophilic surfaces increase the efficiency of the coating, as well as the sensitivity of the method for anti-peptide antibody detection. All peptides were tested by the optimized enzyme-linked immunosorbent assay (ELISA) against 119 sera from patients with primary Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis with anti-Ro/SSA reactivity, 20 sera from patients with systemic diseases without anti-Ro/SSA immune reactivity, as well as against 65 sera from normal individuals. A large proportion of the tested sera reacted against all three peptide analogues, although with a preference for the unmodified form of the epitope. In conclusion, post-translational modifications of the major Ro60 kDa B cell epitope can alter the autoantibody binding.
The role of the cellular prion protein in the immune system
Authors: Isaacs J D , Jackson G S , Altmann D M
Published: August 2006

Prion protein (PrP) plays a key role in the pathogenesis of prion diseases. However, the normal function of the protein remains unclear. The cellular isoform (PrPC) is expressed widely in the immune system, in haematopoietic stem cells and mature lymphoid and myeloid compartments in addition to cells of the central nervous system. It is up-regulated in T cell activation and may be expressed at higher levels by specialized classes of lymphocyte. Furthermore, antibody cross-linking of surface PrP modulates T cell activation and leads to rearrangements of lipid raft constituents and increased phosphorylation of signalling proteins. These findings appear to indicate an important but, as yet, ill-defined role in T cell function. Although PrP–/– mice have been reported to have only minor alterations in immune function, recent work has suggested that PrP is required for self-renewal of haematopoietic stem cells. Here, we consider the evidence for a distinctive role for PrPC in the immune system and what the effects of anti-prion therapeutics may be on immune function.
Methionine‐rich storage protein gene in the rice stem borer, Chilo suppressalis, is expressed during diapause in response to cold acclimation
Authors: Sonoda S. , Fukumoto K. , Izumi Y. , Ashfaq M. , Yoshida H. , Tsumuki H.
Published: August 2006

Gene expressions of acclimatized and non‐acclimatized diapausing larvae were examined in Chilo suppressalis using a subtraction technique. A gene encoding a methionine‐rich storage protein, CsSP1, was cloned and its complete cDNA sequence was determined. Potentially, CsSP1 encoded a 758‐amino acid protein, with a calculated molecular weight of 88.8 kDa. The expression level of CsSP1 was higher in nondiapausing larvae than in diapausing ones. The CsSP1 expression was up‐regulated in diapausing larvae when the temperature of cold acclimation was shifted to 5 °C. The up‐regulated level was maintained at 40 days after incubation at 5 °C. In nondiapausing larvae, CsSP1 expression was down‐regulated when the temperature was below developmental zero. Involvement of CsSP1 in diapause, cold tolerance acquisition and postdiapause development in C. suppressalis is discussed.
Rehydration properties of dried plant tissues
Authors: Witrowa‐Rajchert Dorota , Lewicki Piotr P.
Published: August 2006

Apples, carrots and potatoes cut in cubes were dried by convection and then subjected to rehydration in water at room temperature. Mass and volume changes were followed during rehydration. A minimal displacement gauge was used to record changes of height of individual cubes during wetting. Porosity of the dried material was calculated and its changes during rehydration were observed. Comparing volume increase with mass gain during rehydration it was found that the mechanism of water imbibing is strongly influenced by porosity and chemical composition of the dried material. Dried apple was very porous, hence its mass gain was much faster than the volume increase. On the other hand, gelatinised starch in dried potato strongly absorbed water and the volume increase outpaced the mass gain. Recording changes of height of the dried cubes upon rehydration evidenced phase changes and injury incurred to the tissue structure by dehydration. In apple a collapse of structure was observed, while potato cubes swelled from the very beginning of the wetting process. In carrot instantaneous changes of height of the cube were observed, which could be due to relaxation of shrinkage stresses and displacements of injured tissue structures.
Drying characteristics of textured soy protein
Authors: Cassini Aline S. , Marczak Ligia D. F. , Noreña Caciano P. Z.
Published: August 2006

Textured soy proteins (TSPs) are commonly used as a functional ingredient in several food applications; its process involves a drying step which is one of the most relevant and challenging processes in the food industry. The drying curves of two commercial types of TSPs were determined in a pilot air‐dryer operated at three different drying air temperatures and velocities, with two different heights of product layer. The results showed that drying air temperature significantly influenced all the experimental curves. The height of the product layer influenced only the drying curves of TSP Type I. The effect of drying air velocity was found to be lower. A two‐constant exponential model and a ten‐constant mathematical model were used in the development of a unified model capable of predicting the drying curves of these types of TSP. The experimental curves were successfully predicted in the range of humidity of industrial interest.
Evaluation of electrolysed water as an agent for reducing methamidophos and dimethoate concentrations in vegetables
Authors: Lin Chyi‐Shen , Tsai Pi‐Jen , Wu Christ , Yeh Jui‐Yueh , Saalia Firibu K.
Published: August 2006

In a model system, mixing strong acidic electrolysed oxidising (AC) water with either methamidophos or dimethoate reduced the initial concentrations by more than 99%. Using NaOH solution (pH 11.24) or strong alkaline electrolysed (AK) water resulted in a 98% of methamidophos in 10 min. In contrast, the alkaline solutions only reduced dimethoate concentrations by 35–40%. In food systems, vegetables were soaked in tested pesticide solutions and air‐dried. They were then shaken or ultrasonicated in deionised water, AC water and/or AK water for specified time periods. AK water reduced methamidophos and dimethoate concentrations in leafy cabbage by 33.8% and 31.6%, respectively, and in green pepper by 17.0% and 28.7%, respectively. Continuously changing electrolysed water further decreased the methamidophos and dimethoate concentrations in leafy cabbage by 79.3% and 89.3%, respectively. Electrolysed water was more effective in leafy vegetables than in fruit vegetables because of the pH and the oxidation effect as well as the continuous changing of test solutions.
Nickel homeostasis in Escherichia coli	– the rcnR‐rcnA efflux pathway and its linkage to NikR function
Authors: Iwig Jeffrey S. , Rowe Jessica L. , Chivers Peter T.
Published: August 2006

The nickel physiology of Escherichia coli is dominated by its Ni‐Fe hydrogenase isozymes, which are expressed under anaerobic growth conditions. Hydrogenase activity in E. coli requires the NikABCDE nickel transporter, which is transcriptionally repressed by NikR in the presence of excess nickel. Recently, a nickel and cobalt‐efflux protein, RcnA, was identified in E. coli. This study examines the effect of RcnA on nickel homeostasis in E. coli. Under nickel‐limiting conditions, deletion of rcnA increased NikR activity in vivo. Nickel and cobalt‐dependent regulation of rcnA expression required the newly identified transcriptional repressor RcnR (formerly YohL). Deletion of rcnR results in constitutive rcnA expression and a corresponding decrease in NikR activity. Purified RcnR binds directly to the rcnA promoter DNA fragment and this interaction is inhibited by nickel and cobalt. Nickel accumulation is affected differently among deletion strains with impaired nickel homeostasis. Surprisingly, in low nickel growth conditions rcnA expression is required for nickel import via NikABCDE. The data support a model with two distinct pools of nickel ions in E. coli. NikR bridges these two pools by controlling the levels of the hydrogenase‐associated pool based on the nickel levels in the second pool.
Role of protein phosphatases 2C on tolerance to lithium toxicity in the yeast Saccharomyces cerevisiae
Authors: Ruiz Amparo , González Asier , García‐Salcedo Raúl , Ramos José , Ariño Joaquín
Published: August 2006

Protein phosphatases 2C are a family of conserved enzymes involved in many aspects of the cell biology. We reported that, in the yeast Saccharomyces cerevisiae, overexpression of the Ptc3p isoform resulted in increased lithium tolerance in the hypersensitive hal3 background. We have found that the tolerance induced by PTC3 overexpression is also observed in wild‐type cells and that this is most probably the result of increased expression of the ENA1 Na+‐ATPase mediated by the Hog1 MAP kinase pathway. This effect does not require a catalytically active protein. Surprisingly, deletion of PTC3 (similarly to that of PTC2, PTC4 or PTC5) does not confer a lithium‐sensitive phenotype, but mutation of PTC1 does. Lack of PTC1 in an ena1–4 background did not result in additive lithium sensitivity and the ptc1 mutant showed a decreased expression of the ENA1 gene in cells stressed with LiCl. In agreement, under these conditions, the ptc1 mutant was less effective in extruding Li+ and accumulated higher concentrations of this cation. Deletion of PTC1 in a hal3 background did not exacerbate the halosensitive phenotype of the hal3 strain. In addition, induction from the ENA1 promoter under LiCl stress decreased similarly (50%) in hal3, ptc1 and ptc1 hal3 mutants. Finally, mutation of PTC1 virtually abolishes the increased tolerance to toxic cations provided by overexpression of Hal3p. These results indicate that Ptc1p modulates the function of Ena1p by regulating the Hal3/Ppz1,2 pathway. In conclusion, overexpression of PTC3 and lack of PTC1 affect lithium tolerance in yeast, although through different mechanisms.
The Campylobacter jejuni PhosS/PhosR operon represents a non‐classical phosphate‐sensitive two‐component system
Authors: Wösten Marc M. S. M. , Parker Craig T. , Van Mourik Andries , Guilhabert Magalie R. , Van Dijk Linda , Van Putten Jos P. M.
Published: August 2006

The bacterial pathogen Campylobacter jejuni carries several putative two‐component signal transduction systems of unknown function. Here we report that the PhosS (Cj0889) and PhosR (Cj0890) proteins constitute a two‐component system that is activated by phosphate limitation. Microarray analysis, real‐time RT‐PCR, and primer extension experiments indicated that this system regulates 12 genes (including the pstSCAB genes) present in three transcriptional units. Gel shift assays confirmed that recombinant PhosR protein bound DNA fragments containing the promoter regions upstream of these three transcriptional units. Although functionally similar, the PhosS/PhosR does not exhibit sequence homology with the classical PhoBR systems, has a different pho box (5′‐GTTTCNAAAANGTTTC‐3′) recognized by the C. jejuni response regulator, and is not autoregulated. Because of these atypical properties, we designated the Cj0889‐Cj0890 operon as the C. jejuni PhosS/PhosR system (phosphate sensor/phosphate response regulator) and the phosphate‐regulated genes as the pho regulon of C. jejuni.
AtEXO70A1, a member of a family of putative exocyst subunits specifically expanded in land plants, is important for polar growth and plant development
Authors: Synek Lukáš , Schlager Nicole , Eliáš Marek , Quentin Michaël , Hauser Marie‐Theres , Žárský Viktor
Published: August 2006

The exocyst is a hetero‐oligomeric protein complex involved in exocytosis and has been extensively studied in yeast and animal cells. Evidence is now accumulating that the exocyst is also present in plants. Bioinformatic analysis of genes encoding plant homologs of the exocyst subunit, Exo70, revealed that three Exo70 subgroups are evolutionarily conserved among angiosperms, lycophytes and mosses. Arabidopsis and rice contain 22 and approximately 39 EXO70 genes, respectively, which can be classified into nine clusters considered to be ancient in angiosperms (one has been lost in Arabidopsis). We characterized two independent T‐DNA insertional mutants of the AtEXO70A1 gene (exo70A1‐1 and exo70A1‐2). Heterozygous EXO70A1/exo70A1 plants appear to be normal and segregate in a 1:2:1 ratio, suggesting that neither male nor female gametophytes are affected by the EXO70A1 disruption. However, both exo70A1‐1 and exo70A1‐2 homozygotes exhibit an array of phenotypic defects. The polar growth of root hairs and stigmatic papillae is disturbed. Organs are generally smaller, plants show a loss of apical dominance and indeterminate growth where instead of floral meristems new lateral inflorescences are initiated in a reiterative manner. Both exo70A1 mutants have dramatically reduced fertility. These results suggest that the putative exocyst subunit EXO70A1 is involved in cell and organ morphogenesis.
Treatment of lichen sclerosus with antibiotics
Authors: Shelley Walter B. , Shelley E. Dorinda , Amurao Cristine V.
Published: August 2006

Current therapy for lichen sclerosus centers on topical steroids, particularly clobetasol propionate. As some evidence suggests an infectious etiology owing to Borrelia, we studied the effect of penicillin and cephalosporin therapy on patients with lichen sclerosus who had responded poorly to treatment with potent topical corticosteroids.

Fifteen patients with lichen sclerosus were treated for 3–21 months with either penicillin or cephalosporins in an observational study. Thirteen patients (nine women, four men) received penicillin, including intramuscular penicillin G benzathine suspension and/or oral penicillin V potassium, amoxicillin, or amoxicillin/clavulanate potassium. Two additional men received cephalosporins, either intramuscular ceftriaxone sodium or oral cefadroxil monohydrate.

All patients showed a significant response, evident within a few weeks. Most striking was the rapid relief of pain, pruritus and burning. Four patients cleared completely, four experienced marked improvement, and the remaining seven had a favorable improvement of symptoms with incomplete clearing of lesions.

We recommend treatment of lichen sclerosus with either intramuscular ceftriaxone every 3 weeks or intramuscular penicillin every 2–3 weeks. The addition of oral penicillin or cephalosporin presumably helps maintain antibiotic blood levels and may be a sufficient treatment in some cases.
The importance of IgE antibody levels in anti‐IgE treatment
Authors: Johansson S. G. O. , Öman H. , Nopp A. , Pettersson S.
Published: August 2006

Background:  Dosages of anti‐immunoglobulin (Ig)E in treatment of allergic asthma is based on total IgE body pool assuming that IgE antibodies responsible for the disease are evenly distributed among patients. This assumption was evaluated.

Methods:  Median and quartile concentrations of IgE and IgE antibodies to cat and mite in 6461 sera submitted to an allergy laboratory during 2003–2005 were calculated and expressed in groups of different IgE levels.

Results:  Of 3872 (60%) samples from adults with a serum IgE level of 30–700 kU/l, 22.2% had IgE antibodies (≥0.35 kUA/l) to mite, 36.0% to cat and 8.1% to both. The relative concentration of IgE antibody of IgE decreased with increasing IgE, indicating a more specific response in patients with slightly elevated serum IgE. At a hypothetical serum IgE level of 10 kU/l, the threshold recommended for anti‐IgE treatment, 25% of the originally mite‐ and/or cat‐positive population in the <75 kU/l IgE group still would have detectable IgE antibodies.

Conclusions:  Sera from patients sensitized to mite and cat with moderate serum IgE levels have a high proportion of IgE antibodies; in the 30–74 kU/l group, as much as 10% of the IgE could be specific to one allergen. An increase of the anti‐IgE dosage given to such patients should be considered, especially because IgE antibodies with different, relevant specificities have an additive effect in triggering inflammatory cells.
Bronchial responsiveness to bakery‐derived allergens is strongly dependent on specific skin sensitivity
Authors: Quirce S. , Fernández‐Nieto M. , Escudero C. , Cuesta J. , De Las Heras M. , Sastre J.
Published: August 2006

Background:  Quantitative relationships between immunological reactivity, non‐specific bronchial responsiveness and bronchial responsiveness to allergens have scarcely been investigated in occupational asthma.

Methods:  We assessed the above relationships in 24 subjects with baker's asthma. The skin endpoint titration to bakery allergens as a measure of immunological reactivity, together with the methacholine PC20 and allergen PC20 during early asthmatic reaction were determined.

Results:  All patients had positive skin tests to some bakery allergens (wheat and rye flour, soybean flour, fungal enzymes and egg white proteins) and bronchial hyperresponsiveness to methacholine. Specific inhalation challenge (SIC) tests were performed with aqueous allergen extracts of cereal flour (n = 14), soybean (n = 8), baking enzymes (n = 12), and egg white proteins (n = 8) in sensitized workers. A positive asthmatic reaction was observed in 84% of the inhalation challenges. SIC elicited isolated early asthmatic reactions in 62%, dual reactions in 32% and isolated late reactions in 5%. Multiple linear regression analysis showed allergen PC20 as a function of skin sensitivity to allergen and methacholine PC20, yielding the following highly significant regression formula: log‐allergen PC20 = 0.18 + 0.99 log(skin sensitivity) + 0.343 log(methacholine PC20) (r = 0.89, P < 0.001). This formula predicted allergen PC20 to within one double concentration in 67%, to within two double concentrations in 85% and within three double concentrations in 97%.

Conclusion:  The main determinant of bronchial responsiveness to allergen in patients with baker's asthma is the degree of sensitization to occupational allergens as determined by skin reactivity, modulated to a lesser extent by non‐specific bronchial hyperresponsiveness.
The future of immunotherapy. Report of a National Institute of Allergy and Infectious Diseases (NIAID), Division of Allergy, Immunology and Transplantation (DAIT) Workshop
Authors: Sawyer R. T. , Gergen P. J. , Minnicozzi M. , Plaut M. , Dong G. , Schwaninger J. M. , Fenton M. J.
Published: August 2006

Recent advances in the molecular sciences make possible new and innovative immunotherapeutic approaches to the treatment of human asthma and allergic disorders. In 2005, the National Institute of Allergy and Infectious Diseases, Division of Allergy, Immunology and Transplantation, sponsored a workshop entitled Immunological Basis of Antigen‐specific Asthma/Allergies Therapeutic Strategies Meeting. International experts in the field of asthma and allergy immunotherapy discussed the current state of immunotherapy, and made recommendations for future areas of research aimed at advancing our knowledge and understanding of immunotherapy for asthma and allergic diseases. The workshop recommendations are presented herein.
Detection of clinical unilateral T3a prostate cancer – by digital rectal examination or transrectal ultrasonography?
Authors: Hsu Chao‐Yu , Joniau Steven , Oyen Raymond , Roskams Tania , Van Poppel Hein
Published: August 2006

OBJECTIVE

To assess, in a retrospective study, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of digital rectal examination (DRE), transrectal ultrasonography (TRUS) and the combination of both in unilateral clinical T3a (cT3a) prostate cancer.

PATIENTS AND METHODS

The long‐term outcome of surgical treatment for locally advanced prostate cancer is very good and surpasses that for radiotherapy outcomes, so it is anticipated that surgical management for cT3a disease will become more important, but staging methods for cT3a disease are not well studied. Between 1990 and 2004, 2240 patients had a radical prostatectomy at our institution; 267 were diagnosed as having clinical cT3a prostate cancer either by DRE or TRUS. The final histopathology was compared with the findings of DRE and TRUS. The sensitivity, specificity, PPV and NPV for DRE, TRUS and the combination of both were calculated.

RESULTS

The sensitivity, specificity, PPV and NPV by DRE only was 90.9%, 15.8%, 47.2% and 67.7%, by TRUS only was 80.2%, 25.3%, 47.1% and 60.7%, and by both DRE and TRUS was 71.1%, 41.1%, 50.0% and 63.2%. Although the sensitivity was lower in the combined group, it had the highest specificity (41.1%) and PPV (50.0%). The combination of DRE and TRUS can detect T3a prostate cancer more accurately than either method alone.

CONCLUSION

Until data on staging methods like magnetic resonance imaging become available, the combination of DRE and TRUS is advisable in selecting cT3a patients for primary radical prostatectomy.
Do the Concepts of Grammar and Use in Wittgenstein Articulate a Theory of Language or Meaning?
Authors: Kuusela Oskari
Published: August 2006

The paper elucidates Wittgenstein's later conception of philosophy as devoid of theories or theses, comprehending this as an articulation of a strategy for avoiding dogmatism in philosophy. More specifically, it clarifies Wittgenstein's conception by using what he says about the concepts of meaning and language as an example and by developing an interpretation that purports to make plain that what Wittgenstein says about these issues does not constitute a philosophical thesis. Adopting Wittgenstein's approach, we can, arguably, have a richer view of meaning and language than a commitment to philosophical theses allows for. I conclude with remarks on the method of analysis in terms of necessary conditions.
The Origin of Intentions
Authors: Scheer Richard
Published: August 2006

In contemporary discussions of the concept of intention, the assumption is made that an intention results from a person's decision, or resolution, or plan, or the like. And the intention persists, generally, until the appropriate action is carried out.

However, intentions cannot be said to have temporal duration, or beginnings, or endings. And it is not necessary for a person who is intending to do something to have made a decision to do it, or a resolution, or anything else. It may be that a person acquires an intention because of the circumstances that he finds himself in. If one sees that a tricycle is in front of his car, he will move it. No decision is necessary, obviously, because running over it would be contrary to common sense. Or one may gradually come to realise that he is obliged to do something and thereupon acquires the intention to do it.

By focusing on one kind of intention, the “desire‐belief” theories have failed to realise that intentions originate in various ways, and for various reasons.
The European Research Area: On the Way Towards a European Scientific Community?
Authors: De Elera Álvaro
Published: August 2006

Abstract:  The concept of a European Research Area was launched by the Commission in 2000 with the intention of becoming a watershed in European research policy. The aim was to create an ‘internal market of research’, in contrast with previous efforts in research policy that amounted to continued fragmentation. Lack of support from both Member States and the Council, together with the almost exclusive use of the Open Method of Coordination for the design of the Area, meant that the initially high ambitions were not met. The social repercussions of the project were also watered down as a consequence.
A Mediator on the World Stage?—How the EU's Commitment in Foreign Affairs is Portrayed by New Zealand and Australian Media
Authors: Rogahn Maria , Chaban Natalia , Bain Jessica , Stats Katrina
Published: August 2006

Abstract:  ‘European identity’ is as much a contested concept as is the role of the European Union in foreign affairs. This article combines the two concepts and introduces a third variable, ‘the Other’, in order to address the following questions: How do non‐Europeans perceive the EU on the world stage? Is a tentative identity as a mediator in foreign affairs conveyed in the EU's conduct of foreign policy? Analysing 10 newspapers, 4 television bulletins, and 830 public surveys from Australia and New Zealand in the first half of 2004, this article argues that the EU's efforts to further democracy and peace are often marginalised in Australian and New Zealand perceptions. Nevertheless, subtle traces of perceptions of the EU as a potent global actor promoting human rights and environmental sustainability and challenging unilateral US policy courses were detected.
Investor Protection and International Investment Positions: An Empirical Analysis*
Authors: Cyrus Teresa L. , İşcan Talan B. , Starky Sheena
Published: August 2006

Given the recent revival of interest in the institutional determinants of global capital flows, we investigate the relationship between investor protection and international investment positions, using data on 40 countries for the period 1970–98. We find that strong shareholder protection is an important predictor of gross foreign direct investment liabilities, while countries with strong creditor protection tend to have positive stocks of net foreign assets. We conclude that the global pattern of investor protection is a significant determinant of international investment positions.
The microenvironment of vulvar skin in women with symptomatic and asymptomatic herpes simplex virus type 2 (HSV‐2) infection
Authors: Löwhagen G‐B , Bonde E , Forsgren‐Brusk U , Runeman B , Tunbäck P
Published: August 2006

Background  It is not known why some individuals infected with herpes simplex virus type 2 (HSV‐2), experience frequent recurrences, while most of those infected have a completely silent infection.

Objective  We wanted to study if local factors in the skin could explain this difference.

Design  21 HSV‐2 seropositive patients, 10 with history of >8 clinical recurrences a year (symptomatics) and 11 without symptoms of genital herpes (asymptomatics) were included. All had to answer a questionnaire. With standardised methods, the skin temperature, pH, and the skin barrier function, expressed as transepidermal water loss (TEWL) and skin capacitance, were measured on labium majus and perineum. Culture for bacteria was performed from the same regions.

Results and Conclusion   No significant differences in terms of pH and skin barrier function were registered between symptomatic and asymptomatic patients. Asymptomatic patients had a tendency (0.06) to a higher colonisation with lactobacilli on labium majus than symptomatic patients.
The inflammatory response in drug‐induced acute urticaria: ultrastructural study of the dermal microvascular unit
Authors: Criado PR , Criado RFJ , Valente NYS , Queiroz LB , Martins JEC , Vasconcellos C
Published: August 2006

Background  Drug exposure is one of the main aetiologies of urticaria and represents the second most common cause in acute urticarias. Studies involving the ultrastructural aspects of urticaria are relatively rare in the literature. Most of the articles published report on skin biopsies of experimentally induced urticaria, and acute urticaria has been studied even less from a morphological point of view.

Objectives  The aims of this study were to observe ultrastructural cell characteristics in five patients with drug‐induced acute urticaria and possible aspects of the inflammatory skin response.

Methods  Clinical manifestations, light microscopy and transmission electron microscopy were evaluated.

Results  With light microscopy, a mild perivascular lymphocyte‐monocyte infiltrate was observed with few neutrophils and dermal oedema in skin biopsies of five patients. With electron microscopy, a mild vascular dilatation was observed, with platelets in the lumen and several lymphocytes and dendritic cells close to the superficial dermal vessels. Some mast cells appeared normal, whereas others were granule‐depleted. In some areas, mast cells, lymphocytes and satellite dendritic cells were closely associated, as well as some macrophages. A significant number of plasma cells, eosinophils and polymorphonuclear neutrophils were not observed; however, the presence of lymphocytes and macrophages was significant. The epidermis and the dermal‐epidermal junction were preserved, except for a discrete oedema in keratinocytes.

Conclusions  The ultrastructural aspect of drug‐induced acute urticaria is similar to that observed in urticaria caused by Urtica dioica, intradermal histamine and cold urticaria. The presence of the cellular triad with mast cells, dendritic (or satellite) cells and lymphocytes suggests a functional interaction of these cells. These findings support the possible existence of mechanisms in the dermis that may participate in protective and/or injurious vasocentric immune reactions.
Robert Martin
Authors: Holman Andrew
Published: August 2006

Accessible Summary

Robert Martin has probably done more for the rights of people with learning difficulties than anyone else.

He has been a leader in the self advocacy movement for 25 years.

He travels all over the world talking about his work.

He is now working on the rights of people with learning difficulties and disabled people with the UN (United Nations).
A new movement in an old bureaucracy: the development of self‐advocacy in the Czech Republic
Authors: Šiška Jan
Published: August 2006

Accessible Summary

In this paper I describe how self‐advocacy has grown in the Czech Republic.

First, I talk about how services for people with learning disabilities have begun to change in the last few years. This is because voluntary groups have lobbied and campaigned for change.

I learned about self‐advocacy during a visit to the UK in the 1990s. I went back to the Czech Republic and asked some service users I knew whether they would like to start the country's first self‐advocacy group. They agreed and since then the group has grown and developed new networks.

The group has also received some financial and practical support from the biggest parents’ organization for people with learning disabilities in the Czech Republic.

A number of conferences have been organized by self‐advocates, including one at the Czech Republic Parliament. Other people are now starting to take notice of what self‐advocates are saying.

Support for self‐advocacy is an important issue for its future in the Czech Republic.
Japanese culture and the philosophy of self‐advocacy: the importance of interdependence in community living
Authors: Tsuda Eiji
Published: August 2006

Accessible Summary

In Japan, there is a growing network of self‐advocacy groups. Some groups are involved in campaigning. Other groups are involved in social events and education.

The age of de‐institutionalization is gradually arriving and community living for people with learning difficulties is becoming an urgent political issue.

Self‐advocacy groups can help people to settle and be accepted in the community.

It is important to think about how self‐advocacy ideas will fit with traditional parts of Japanese culture.
Learning about self‐advocacy from life history: a case study from the United States*
Authors: Traustadóttir Rannveig
Published: August 2006

Accessible Summary

Many people with learning difficulties want to tell the stories of their life and have done so in collaboration with academic researchers.

Life histories of people with learning difficulties are a good way to learn about self‐advocacy. Life histories can tell us about how self‐advocacy began and the support people need to be self‐advocates.

Tom Allen lived in institutions for 60 years. His life history describes how he could speak up about his wishes, the people who helped him speak up and how he was able to move out of the institution.
Challenging the monologue about silent sterilization: implications for self‐advocacy
Authors: Roets Griet , Adams Marie , Hove Geert Van
Published: August 2006

Accessible Summary

This is the story of Marie, a woman with ‘learning difficulties’ who lives in Belgium. It is told by Marie and her advocate, Griet. In 2002, Marie was told she had to have a sterilization. This is the story of what happened:

The professionals told Marie and her mother the operation was essential.

Marie did not know what the operation was because the professionals did not explain what it meant nor did they talk through this difficult issue with her. She discussed it with Griet; Marie did not want it because it was not necessary. They agreed to refuse it.

They conclude that sterilization has to be a choice made by the woman concerned and not forced on someone because they are labelled as having ‘learning difficulties’.
Narrating, writing, reading: life story work as an aid to (self) advocacy
Authors: Meininger Herman P.
Published: August 2006

Accessible Summary

This article is about life story work with people with learning disabilities. It talks about reading and writing stories, and listening to them.

Telling your life story, writing it down and talking about it with others can be an important part of self‐advocacy for people with learning disabilities.

Life stories are helpful when they are told or written in a way that brings back memories that tell you about the real person. They should be written in a clear and honest way. These stories are very important, and other people need to listen to or read them in a careful and respectful way.

Life stories show how each person is special and an individual in their own right, with their own history. This is not the case in the files and records of most service organizations.

Life story work can help people with learning disabilities to feel good about themselves and to understand themselves better.

It also helps support workers and others to see each person with learning disabilities as an individual, to understand important relationships, and the ways in which the person they are working with makes sense of his or her life.
Isoprenoid metabolism and plastid reorganization in arbuscular mycorrhizal roots
Authors: Strack Dieter , Fester Thomas
Published: August 2006

Plant root‐colonizing arbuscular mycorrhizal (AM) fungi activate the methylerythritol phosphate pathway, carotenoid biosynthesis and oxidative carotenoid cleavage in roots, leading to C13 and C14 apocarotenoids, that is, cyclohexenone and mycorradicin derivatives. Mycorradicin causes the characteristic yellow coloration of many AM roots accumulating within a complex mixture of unknown components. The accumulating C13 cyclohexenones exhibit various ring substitutions and different glycosyl moieties. Transcript levels of the first two enzymes of the MEP pathway, 1‐deoxy‐d‐xylulose 5‐phosphate synthase and 1‐deoxy‐d‐xylulose 5‐phosphate reductoisomerase, and of the carotenoid pathway, phytoene desaturase and ζ‐carotene desaturase, along with a carotenoid‐cleaving dioxygenase, are markedly increased in AM roots. This correlates with proliferation and reorganization of root plastids. These results allow at this point only speculation about the significance of apocarotenoid accumulation: participation in the production of signaling molecules and control of fungal colonization or protection against soil‐borne pathogens; protection of root cells against oxidative damage of membranes by reactive oxygen species; and promotion of the symbiotic interactions between plant roots and AM fungi.

Contents

Summary
22

I.
Introduction
23

II.
Mycorradicin
23

III.
Cyclohexenone derivatives
24

IV.
Occurrence of apocarotenoids
24

V.
Biosynthesis of apocarotenoids
25

VI.
Root plastids
27

VII.
Significance of carotenoid metabolism
29

Acknowledgements
32

References
32
Household production of sorghum beer in Benin: technological and socio‐economic aspects
Authors: Kayodé A.P. Polycarpe , Hounhouigan D. Joseph , Nout Martinus J.R. , Niehof Anke
Published: August 2006

This study evaluated the sorghum brewing microenterprises in Benin with emphasis on the beer quality, the social significance of the product as well as the income generated.Tchoukoutou, the Benin opaque sorghum beer, has important social functions as it fosters the cooperative spirit and remains an ancestral beverage widely used for traditional ceremonies. The manufacturing process consists of malting (soaking, germination and sun drying), brewing (mashing, boiling, filtration) and fermentation. The beer is sour with a pH of 3.2 and contains a relatively high but variable level of solids and crude protein. Most of the consumers appreciate an opaque, sour and pink‐coloured beer. The consumers related many of the beer properties to health effects. Participants can link the perceived qualities of the beer to the grain’s functional properties, and this leads to the classification of the farmers’ sorghum as varieties of top, medium and low quality for brewing. The profits fromtchoukoutouproduction range from 2365 to 17 212 fcfa per month (1 euro = 656 fcfa) for the producers, depending on beer yield and quantity of raw grain transformed. The generated income is used for household needs and part of it is invested in children’s education.
Factors affecting Internet shopping behaviour in Singapore: gender and educational issues
Authors: Hui Tak‐Kee , Wan David
Published: August 2006

Despite the increasing number of online users and products that are being offered on the Web, there is relatively little work that specifically examines the role of gender and educational level on the attitudes of Internet users in the Singapore context. Our findings reveal that there is a general consensus amongst Singaporeans that the Internet is a convenient medium for information search or making purchases. The better‐educated respondents seem to be less concerned with security issues. They also perceive that Internet shopping provides better prices and more cost savings. Females indicate a strong dislike for not being able to savour a physically fulfilling shopping experience online.