bluuebunny/crossref_metadata_2025 huggingface dataset:
The Paradox of the Lesbian Worker
Authors: Peplau Letitia Anne , Fingerhut Adam
Published: November 2004

Common sense might suggest that lesbian workers are doubly disadvantaged due to their gender and their stigmatized sexual orientation. But empirical research documents that lesbian workers earn more than their heterosexual women peers. This article considers two reasons for the economic advantage of lesbian workers. First, because lesbians must provide for themselves and their children, they may pursue nontraditional, higher‐paying jobs and show increased work motivation. Second, stereotypes may depict lesbians, including lesbian mothers, as competent and committed workers. A review of available research is augmented with data from a study of 162 college students. Results indicate that motherhood detracts from the perceived work commitment and competence of heterosexual mothers but not lesbian mothers. Directions for future research are considered.
Processes of Change in Work/Home Incompatibilities: Employed Mothers 1986–1999
Authors: Tiedje Linda Beth
Published: November 2004

This study examined multi‐level change processes occurring in the lives of employed mothers in response to work and family incompatibilities. Data were collected from 158 professional women in seven waves of data spanning 13 years. The data were subjected to qualitative analysis following Colaizzi's (1978) method. Seven themes emerged: (a) individual mutabilities, (b) James Baldwin's paradox, (c) time enough (d) coping, (e) incremental change, (f) new occasions teach new duties, and (g) strength from others.
Gender aspects of the use of English on a South African university campus
Authors: De Kadt Elizabeth
Published: November 2004

Abstract:  This paper seeks an explanation for the current tendency of female students at the University of KwaZulu‐Natal, Durban, South Africa, to select English rather than their L1, isiZulu, for social interactions with Zulu peers. I draw on Labov’s (2001) findings on the prominent role of women in language change, recent work on language shift and changing conceptualizations of gender. I take as given macro factors and instead explore gendered self‐perceptions which might predispose speakers to select one language over the other. I draw on qualitative perception and attitudinal data collected by myself and Zulu research assistants, by means of interviews and focus groups. After discussing labels commonly used, in several languages, for men and women on campus, I consider interactional goals which may be underlying the choice of English: the desire to express politeness and respect, to embody ‘campus style’, to negotiate changing relations with parents, and finally, to negotiate equitable relationships with male students on campus. I conclude that this instance of growing use of English is linked to continued gender inequity in South Africa, and does not necessarily imply impending language shift.
Obstruent voicing and devoicing in the English of Cantonese speakers from Hong Kong
Authors: Peng Long , Ann Jean
Published: November 2004

Abstract:  This study offers a description and analysis of consonant voicing and devoicing in the L2 English of Cantonese speakers from Hong Kong. Focusing on stem‐final voiced obstruents in distinct structural environments, we find that the rates of voicing and devoicing vary with the environment. Stem‐final obstruents are more likely to devoice in prevoiceless and word‐final positions than in prevocalic and pre‐sonorant positions. Our analysis reveals a systematic pattern, expressible by three ranked constraints: IdOn(Lar)»*Lar» Id(Lar). This ranking retains to a large extent the ranking relations of the constraints in Cantonese. Our finding suggests that transfer plays a significant role in shaping the L2 English ranking. The comparison with L1 English shows that the two varieties are distinct, providing further evidence for a distinct Hong Kong English accent (Hung, 2000) and for the emergence of a distinct variety of English with unique sound structures (Peng and Setter, 2000).
Biology of IL‐21 and the IL‐21 receptor
Authors: Mehta Devangi S. , Wurster Andrea L. , Grusby Michael J.
Published: November 2004

Summary:  Interleukin‐21 (IL‐21) is the newest member of the common γ‐chain family of cytokines, which includes IL‐2, IL‐4, IL‐7, IL‐9, IL‐13, and IL‐15. Its private receptor, IL‐21R, has been shown to activate the Janus kinase/signal transducers and activators of transcription signaling pathway upon ligand binding. Initial studies have demonstrated that IL‐21 has pleiotropic effects on the proliferation, differentiation, and effector functions of B, T, natural killer, and dendritic cells. More recently, the potential therapeutic capacity of IL‐21 in the treatment of cancers has been widely investigated. The biological role of IL‐21 in the immune system is complex, as IL‐21 has been shown to have the ability to both promote and inhibit immune responses. Overall, the current data point to IL‐21 being a novel immunomodulatory cytokine, whose regulation of any given immune response is highly dependent on the surrounding environmental context.
Natural antibody response to Plasmodium falciparum Exp‐1, MSP‐3 and GLURP long synthetic peptides and association with protection
Authors: Meraldi V. , Nebié I. , Tiono A. B. , Diallo D. , Sanogo E. , Theisen M. , Druilhe P. , Corradin G. , Moret R. , Sirima B. S.
Published: November 2004

A longitudinal study was undertaken in Burkina Faso among 293 children aged 6 months to 9 years in order to determine the correlation between an antibody response to several individual malarial antigens and malarial infection. It was found that the presence of a positive antibody response at the beginning of the rainy season to three long synthetic peptides corresponding to Plasmodium falciparum Exp‐1 101–162, MSP‐3 154–249 and GLURP 801–920 but not to CSP 274–375 correlated with a statistically significant decrease in malarial infection during the ongoing transmission season. The simultaneous presence of an antibody response to more than one antigen is indicative of a lower frequency of malarial infection. This gives scientific credibility to the notion that a successful malaria vaccine should contain multiple antigens.
Research on Divorce, Separation and Family Change: Messages for Practitioners
Authors: Douglas Gillian , Davies Máire Messenger , Doughty Julie
Published: November 2004

The JRF has supported a series of twelve research projects about the effects of divorce and separation. This paper highlights key messages and common themes that emerge for practitioners working with children and their families.
Re‐Emphasizing the Role of Affect in Learning and Teaching
Authors: Le Cornu Rosie , Collins Janet
Published: November 2004

Issues of combating social exclusion are often held to be synonymous with a reduction of truancy and exclusion from schools. In the UK, for example, the Labour Party has expressed a commitment to reducing the number of pupils truanting or excluded from our schools Social Exclusion Unit (SEU) (1998). As this paper will illustrate however, the social exclusion of pupils goes way beyond simple measures of school attendance. Equally important are issues of affect, the external, observable manifestation of emotion and feeling, which are related to the engagement and active participation of pupils in schools. Drawing on years of teaching and research in Australia and the UK, this paper examines the role of affect in learning and teaching. We begin by examining the ways in which pupils' participation and inclusion is related to their perceptions of themselves, the quality of their relationships in school and their feelings about the culture of the classrooms in which they work. We then examine the ways in which teachers' perceptions of themselves and their feelings about the culture of the school in which they work influences how they teach and indeed how they learn. We argue that constructivist approaches to learning provide an opportunity for pupils, and teachers, to feel more included, rather than excluded, from the education process.
Bounding Analysis as an Inadequately Specified Methodology
Authors: Greenland Sander
Published: November 2004

The bounding analysis methodology described by Ha‐Duong et al. (this issue) is logically incomplete and invites serious misuse and misinterpretation, as their own example and interpretation illustrate. A key issue is the extent to which these problems are inherent in their methodology, and resolvable by a logically complete assessment (such as Monte Carlo or Bayesian risk assessment), as opposed to being general problems in any risk‐assessment methodology. I here attempt to apportion the problems between those inherent in the proposed bounding analysis and those that are more general, such as reliance on questionable expert elicitations. I conclude that the specific methodology of Ha‐Duong et al. suffers from logical gaps in the definition and construction of inputs, and hence should not be used in the form proposed. Furthermore, the labor required to do a sound bounding analysis is great enough so that one may as well skip that analysis and carry out a more logically complete probabilistic analysis, one that will better inform the consumer of the appropriate level uncertainty. If analysts insist on carrying out a bounding analysis in place of more thorough assessments, extensive analyses of sensitivity to inputs and assumptions will be essential to display uncertainties, arguably more essential than it would be in full probabilistic analyses.
Pathway Analysis for Population‐Total Health Impacts of Toxic Metal Emissions
Authors: Spadaro Joseph V. , Rabl Ari
Published: November 2004

This article describes a simple model for quantifying the health impacts of toxic metal emissions. In contrast to most traditional models it calculates the expectation value of the total damage (summed over the total population and over all time) for typical emission sites, rather than “worst‐case” estimates for specific sites or episodes. Such a model is needed for the evaluation of many environmental policy measures, e.g., the optimal level of pollution taxes or emission limits. Based on the methodology that has been developed by USEPA for the assessment of multimedia pathways, the equations and parameters are assembled for the assessment of As, Cd, Cr, Hg, Ni, and Pb, and some typical results are presented (the dose from seafood is not included and for Hg the results are extremely uncertain); the model is freely available on the web. The structure of the model is very simple because, as we show, if the parameters can be approximated by time‐independent constants (the case for the USEPA methodology), the total impacts can be calculated with steady‐state models even though the environment is never in steady state. The collective ingestion dose is found to be roughly 2 orders of magnitude larger than the collective dose via inhalation. The uncertainties are large, easily an order of magnitude, the main uncertainties arising from the parameter values of the model, in particular the transfer factors. Using linearized dose‐response functions, estimates are provided for cancers due to As, Cd, Cr, and Ni as well as IQ loss due to Pb emissions in Europe.
The Maximally Exposed Individual—Comparison of Maximum Likelihood Estimation of High Quantiles to an Extreme Value Estimate
Authors: Wilson Machelle D. , McCormick William P. , Hinton T. G.
Published: November 2004

The dose to human and nonhuman individuals inflicted by anthropogenic radiation is an important issue in international and domestic policy. The current paradigm for nonhuman populations asserts that if the dose to the maximally exposed individuals in a population is below a certain criterion (e.g., <10 mGy d−1) then the population is adequately protected. Currently, there is no consensus in the regulatory community as to the best statistical approach. Statistics, currently considered, include the maximum likelihood estimator for the 95th percentile of the sample mean and the sample maximum. Recently, the investigators have proposed the use of the maximum likelihood estimate of a very high quantile as an estimate of dose to the maximally exposed individual. In this study, we compare all of the above‐mentioned statistics to an estimate based on extreme value theory. To determine and compare the bias and variance of these statistics, we use Monte Carlo simulation techniques, in a procedure similar to a parametric bootstrap. Our results show that a statistic based on extreme value theory has the least bias of those considered here, but requires reliable estimates of the population size. We recommend establishing the criterion based on what would be considered acceptable if only a small percentage of the population exceeded the limit, and hence recommend using the maximum likelihood estimator of a high quantile in the case that reliable estimates of the population size are not available.
Addressing Nonlinearity in the Exposure‐Response Relationship for a Genotoxic Carcinogen: Cancer Potency Estimates for Ethylene Oxide
Authors: Kirman C. R. , Sweeney L. M. , Teta M. J. , Sielken R. L. , Valdez‐Flores C. , Albertini R. J. , Gargas M. L.
Published: November 2004

Ethylene oxide (EO) has been identified as a carcinogen in laboratory animals. Although the precise mechanism of action is not known, tumors in animals exposed to EO are presumed to result from its genotoxicity. The overall weight of evidence for carcinogenicity from a large body of epidemiological data in the published literature remains limited. There is some evidence for an association between EO exposure and lympho/hematopoietic cancer mortality. Of these cancers, the evidence provided by two large cohorts with the longest follow‐up is most consistent for leukemia. Together with what is known about human leukemia and EO at the molecular level, there is a body of evidence that supports a plausible mode of action for EO as a potential leukemogen. Based on a consideration of the mode of action, the events leading from EO exposure to the development of leukemia (and therefore risk) are expected to be proportional to the square of the dose. In support of this hypothesis, a quadratic dose‐response model provided the best overall fit to the epidemiology data in the range of observation. Cancer dose‐response assessments based on human and animal data are presented using three different assumptions for extrapolating to low doses: (1) risk is linearly proportionate to dose; (2) there is no appreciable risk at low doses (margin‐of‐exposure or reference dose approach); and (3) risk below the point of departure continues to be proportionate to the square of the dose. The weight of evidence for EO supports the use of a nonlinear assessment. Therefore, exposures to concentrations below 37 μg/m3 are not likely to pose an appreciable risk of leukemia in human populations. However, if quantitative estimates of risk at low doses are desired and the mode of action for EO is considered, these risks are best quantified using the quadratic estimates of cancer potency, which are approximately 3.2‐ to 32‐fold lower, using alternative points of departure, than the linear estimates of cancer potency for EO. An approach is described for linking the selection of an appropriate point of departure to the confidence in the proposed mode of action. Despite high confidence in the proposed mode of action, a small linear component for the dose‐response relationship at low concentrations cannot be ruled out conclusively. Accordingly, a unit risk value of 4.5 × 10−8 (μg/m3)−1 was derived for EO, with a range of unit risk values of 1.4 × 10−8 to 1.4 × 10−7 (μg/m3)−1 reflecting the uncertainty associated with a theoretical linear term at low concentrations.
Some Bayesian Experimental Design Theory for Risk Reduction in Extrapolation
Authors: LuValle Michael J.
Published: November 2004

Decision problems depending on extrapolation promise to become increasingly important. The key problem is determining if the model being used for extrapolation is going to give reasonable results, or err in a dangerous manner. Ideally, as one proceeds from investigation to decision, some guidance should be present based on the goal as to which investigation will reduce the risk the most given the cost. In this report, a very simple version of the problem is formalized and examined. The result is, interestingly, that the best evidence in support of the favored model is a null result in the experiment most likely to raise doubt over that model. The theory is applied to a simple example drawn from accelerated testing.
Expert and Public Perception of Risk from Biotechnology
Authors: Savadori Lucia , Savio Stefania , Nicotra Eraldo , Rumiati Rino , Finucane Melissa , Slovic Paul
Published: November 2004

Risk perceptions of a series of biotechnology applications were examined in a public (nonexpert) sample and an expert sample. Compared with the experts, the public perceived all biotechnology applications as more risky. Both groups perceived food‐related applications to be riskier than medical applications. Compared with the public, experts perceived both food and medical applications as less harmful and more useful. Experts also judged the risks posed from medical biotechnology applications as more familiar and acknowledged by people and science. Lay estimates of the risk of food applications were predicted by potential harm, potential benefits, science knowledge, and familiarity; experts' estimates were predicted only by harm and benefits. Lay estimates of the risk of medical applications were predicted by potential harm; experts' estimates were predicted by potential benefits, number and type of people exposed, and science knowledge. We discuss the implications of the results for risk communication about and management of different types of biotechnologies.
Intended Message Versus Message Received in Hypothetical Physician Risk Communications: Exploring the Gap
Authors: Gurmankin Andrea D. , Baron Jonathan , Armstrong Katrina
Published: November 2004

We examined the risk perception that is derived from hypothetical physician risk communications. Subjects (n= 217) completed a questionnaire on the Web for $3. Subjects were presented with four hypothetical cancer risk scenarios that included a physician risk communication in one of three risk communication formats: verbal only, verbal plus numeric probability as a percent, and verbal plus numeric probability as a fraction. In each scenario, subjects were asked to imagine themselves as the patient described and to state their perceived personal susceptibility to the cancer (i.e., risk perception) on a 0 to 100 scale, as well as responses to other measures. Subjects' risk perceptions were highly variable, spanning nearly the entire probability scale for each scenario, and the degree of variation was only slightly less in the risk communication formats in which a numeric statement of risk was provided. Subjects were more likely to overestimate than underestimate their risk relative to the stated risk in the numeric versions, and overestimation was associated with the belief that the physician minimized the risk so they wouldn't worry, innumeracy, and worry, as well as decisions about testing for the cancer. These results demonstrate significant gaps between the intended message and the message received in physician risk communications. Implications for medical decisions, patient distress, and future research are discussed.
Effects of Context and Feelings on Perceptions of Genetically Modified Food
Authors: Townsend Ellen , Clarke David D. , Travis Betsy
Published: November 2004

Recently, there has been a surge of interest in the role of feelings in framing perceptions and decisions about risk, yet no study has specifically examined the impact of feelings on perceptions/judgments about biotechnology. This exploratory study investigated current perceptions of genetically modified (GM) food to examine (1) the effects of context (making judgments about GM food at the same time as rating other current areas of concern), and (2) the effect of feelings of dread (integral affect) and background feelings of stress (negative incidental affect) on risk judgments about GM food. An established psychometric method (semantic differential task) used with a sample of 126 adults (recruited “topic‐blind,” mostly from a student population) showed that, when rated in the context of other current concerns such as human cloning and Creutzfeldt‐Jakob disease (CJD), there was less concern about GM food than might have been anticipated. Participants were recruited “topic‐blind” in order to ensure that they were unaware that the focus of the research was on GM food specifically (and thus preventing biased recruitment to the study). Relative to 19 other current concerns GM food was “not dreaded,” not viewed as “unethical,” was judged as “controllable,” and was seen as the least “risky” of all the issues studied. GM food was viewed as a “hot topic,” a new risk, and as relatively unnatural (although it was not the highest rated concern on this scale). Ratings of risks across concerns by individuals experiencing high levels of negative incidental affect (stress) did not differ significantly from those reporting low stress.
Evaluation of the Allergenicity and Antigenicity of Bovine‐Milk αs1‐Casein Using Extensively Purified Synthetic Peptides
Authors: Elsayed S. , Hill D. J. , Do T. V.
Published: November 2004

αs1‐Casein (CAS1_BOVIN), the major allergen of cow's milk (CM), is widely used as hydrolysates in infant diet formulae and additive to other processed food items. To date, most of the reported B‐cell epitope mapping were performed on polyethylene pins or cellulose‐derivative membrane. We sought to locate the motifs critical for human‐specific IgE and rabbit polyclonal IgG binding using extensively purified CAS1_BOVIN, synthetic peptides and derivatives. Thirteen overlapping peptides covering the whole CAS1_BOVIN encompassing 17 : 20 amino acid (AA) were synthesized by f‐moc AA solid‐phase polyamide peptide synthesis. In addition, six cyanogen bromide (CNBr) cleavage fragments were prepared. Limited hydrolysis, oxidized and reduced/alkylated derivatives were also produced. The preparations were purified by ion exchange, gel filtration chromatography, reversed phase and high‐performance liquid chromatography. The homogeneity was visualized by sodium dodecyl sulfate (SDS) and poly acryl amide gel electrophoresis (PAGE) followed by IgE and IgG immunoblotting. IgE binding was measured by Biotin Streptavidin (Bio/strep) fluoro enzyme immuno assay (FEIA) or ELISA‐inhibition. Eighteen CM allergy (CMA) sera from 45 clinically examined children (Melbourne) and five adults (Bergen) were selected. Individual sera and pools were used for mapping IgE‐binding epitopes. Rabbit IgG sera and pools were used for locating the antigenic sites of the molecule. Results indicated that all the individual CMA sera and pools recognized the intact molecule and three of the CNBr fragments as major antibody‐binding allergens. The N‐ and C‐terminal peptides (CAS 16‐35; CAS 136‐155) showed high IgE‐binding affinity. CAS 1‐18 and CAS 181‐199 showed high IgG bindings. Considering the diversity of the antibody specificities, a reasonable agreement between IgE and IgG epitopes were found at the N‐ and C‐terminals of CAS1_BOVIN. Mapping IgE B‐cell epitopes by direct Bio/strep FEIA allowed the development of a sensitive modified technique for detecting unlabelled, casein immune dominant peptides in food products.
Expression of Interleukin‐22 in Murine Carcinoma Cells did not Influence Tumour Growth In Vivo but did Improve Survival of the Inoculated Hosts
Authors: Nagakawa H. , Shimozato O. , Yu L. , Takiguchi Y. , Tatsumi K. , Kuriyama T. , Tagawa M.
Published: November 2004

Interleukin (IL)‐22, a novel cytokine belonging to the IL‐10 family, is secreted from activated T and natural killer cells and is possibly involved in inflammatory responses. We examined whether expression of the IL‐22 gene in murine colon carcinoma Colon 26 cells (Colon 26/IL‐22) could produce any antitumour effects in the inoculated mice. Although growth of Colon 26/IL‐22 tumours in syngeneic mice was not different from that of parent tumours, survival of the mice that were subcutaneously or intraperitoneally inoculated with Colon 26/IL‐22 tumours was significantly prolonged compared with the mice inoculated with parent tumours. Metastasis was not influenced by IL‐22 expressed in tumours. Expression of the IL‐22 receptor‐specific gene, IL‐22R, was not induced in spleen cells stimulated with concanavalin A, anti‐CD3 or anti‐CD40 antibody, despite constitutive expression of the IL‐10R2 gene, which encodes another component of the heterodimeric IL‐22 receptor complex. IL‐22 thereby does not directly act on immunocompetent cells, and IL‐22 expressed in tumours can favour apothanasia of inoculated hosts.
Past Returns and Investment Trust Discounts
Authors: Bleaney Michael
Published: November 2004

Abstract:  The relationship between past net asset value returns and the current discount on investment trusts is investigated. The relationship is weaker for the component that is common to all trusts in the same sector, and is significantly stronger for more liquid trusts. The time lag before returns have their full impact on discounts is consistent with the requirements of distinguishing ‘skill’ from noise. Although discounts vary widely even within the same sector, the range of variation appears to be consistent with an arbitrage equilibrium, in which the profits of exploiting apparent pricing anomalies are just insufficient to invite arbitrage trades.
Helping People is a Democratic Process
Authors: King Pauline E.
Published: November 2004

Editor's Note  Deciding when to assist and when to stand back so that individuals may follow their own desires has been a source of much public debate in the last few years with respect to health behaviors, social structures, and also political beliefs. The following short essay, published in the July 1948 issue of the first Public Health Nursing, illustrates, first, that from flawed logic we derive flawed conclusions, but also maybe a modicum of truth. Secondly, it aptly highlights the conundrum of “incentives” and the disillusionment of well‐meaning “givers” when the recipients do not view our “gifts” through the same lens. We do not subscribe to the views of Ms. King, but rather raise the following questions for your consideration, “When we give, how much are we meeting our own needs rather than the needs of others?”“Can a society be empathic without losing its own sense of identity?” Things to ponder in this holiday season …
Number, frequency, self‐renewal, and expansion of osteoprogenitor cells (CFU‐O) in subcultured female rat vertebral cell populations
Authors: Bellows Carlton G. , Pei Weidong , Heersche Johan N.M.
Published: November 2004

The present study was undertaken to determine whether the frequency and/or number of dexamethasone‐ and progesterone‐responsive osteoprogenitors in cell populations derived from vertebrae of 6‐week‐old female rats could be increased relative to that of other progenitors. Frequencies and numbers of both progenitor types were determined for up to six subcultures using continuous subculturing, limiting dilution analysis, and colony assays. In dexamethasone‐containing medium, subculturing resulted in an eightfold increase in the total number of dexamethasone‐responsive osteoprogenitors and a 14‐fold increase in progesterone‐responsive osteoprogenitors in second subculture cells over first subculture cells without a significant increase in the frequency of these progenitors. From the third subculture onward, the frequency of both classes of osteoprogenitors decreased in a linear manner and none were observed after six subcultures. Similar results were obtained in progesterone‐containing medium. Limiting dilution analysis in the presence of dexamethasone indicated that 2.61 % of cells represented a colony forming unit‐fibroblast and 0.28 % represented an osteoprogenitor in first subculture cells, while in second subculture cells, these frequencies increased to 5.56 % and 0.40 %, respectively. Results show that while the frequency of colony forming unit‐osteoprogenitor is not increased in the second subculture over the first, the total number of osteoprogenitors is greatly increased because of expansion of the total progenitor cell pool.
Assessment of signal transducer and activator of transcription 6 as a target of glucocorticoid action in human airway epithelial cells
Authors: Heller N. M. , Matsukura S. , Georas S. N. , Boothby M. R. , Stellato C. , Schleimer R. P.
Published: November 2004

BackgroundActivation of signal transducer and activator of transcription (STAT)6 by IL‐4 and IL‐13 is essential in many key epithelial responses in the asthmatic airway including expression of numerous chemokines, goblet cell differentiation and mucus production and expression of other allergic inflammatory genes. While these responses are all inhibited by glucocorticoids (GC) administered systemically or by inhalation, the inhibitory mechanisms are unknown.

ObjectiveTo test the hypothesis that GC suppress allergic responses by blocking IL‐4‐induced STAT6 signalling in airway epithelial cells.

MethodsWestern blotting and reporter gene assays were used to determine whether GC could inhibit STAT6 production, phosphorylation or nuclear translocation, or whether GC could affect STAT6 transcriptional activity in the BEAS‐2B airway epithelial cell line.

ResultsOur results showed that GC had no inhibitory effect on the total cellular or nuclear levels of STAT6 or phospho‐STAT6. GC did not inhibit transcription from three different STAT6‐driven reporter constructs, indicating that GC also did not inhibit STAT6 function.

ConclusionWe conclude that airway epithelial STAT6 is not the central target of GC in allergic inflammation and that the inhibitory effect of GC on STAT6‐mediated IL‐4‐ and IL‐13‐induced responses is exerted by targeting pathways distinct from STAT6.
Prophylactic management of children at risk for recurrent upper respiratory infections: the Preventia I Study
Authors: Grimfeld A. , Holgate S. T. , Canonica G. W. , Bonini S. , Borres M. P. , Adam D. , Canseco Gonzalez C. , Lobaton P. , Patel P. , Szczeklik A. , Danzig M. R. , Roman I. , Bismut H. , Czarlewski W.
Published: November 2004

Background
Given the morbidity and mortality of asthma and the recent dramatic increase in its prevalence, pharmacologic prophylaxis of this disease in children at risk would represent a major medical advance.

Objectives
The Preventia I Study was designed to evaluate the efficacy and long‐term safety of loratadine in reducing the number of respiratory infections in children at 24 months. A secondary objective was to investigate the benefit of loratadine treatment in preventing the onset of respiratory exacerbations.

Methods
Preventia I was a randomized placebo‐controlled study involving 22 countries worldwide. The children were 12–30 months of age at enrolment and had experienced at least five episodes of ENT infections, and no more than two episodes of wheezing during the previous 12 months. Phase I was a 12‐month double‐blind period during which the children were treated with loratadine 5 mg/day (2.5 mg/day for children24 months of age) or placebo. Phase II was a double‐blind follow‐up period without study medication.

Results
Of the 412 children enrolled, 342 and 310 completed Phase I and Phase II, respectively. The results showed a significant decrease in the number of infections in the whole population of children. However, no difference was observed between the loratadine and placebo group. When considering secondary end‐points, loratadine was shown to reduce the number of respiratory exacerbations during the treatment phase. None of the 204 children who received loratadine discontinued the study because of drug‐related events. Loratadine treatment was not more sedative than placebo and was not associated with cardiovascular events.

Conclusion
The strong decrease in the rate of infections in the children at risk of recurrent infections, while not being influenced by loratadine treatment, should encourage future reflection in terms of prophylactic management. This study also confirms the long‐term safety of loratadine and its metabolites in young children.
Detection of tryptase−, chymase+ cells in human CD34+ bone marrow progenitors
Authors: Shimizu Y. , Suga T. , Maeno T. , Tsukagoshi H. , Kawata T. , Narita T. , Takahashi T. , Ishikawa S. , Morishita Y. , Nakajima T. , Hara F. , Miura T. , Kurabayashi M.
Published: November 2004

Background
Mast cells (MCs) arise from haematopoietic stem cells. We have recently reported that CD34+ progenitors derived from human bone marrow (BM) develop into tryptase+, chymase+ MCs when cultured in the presence of recombinant human stem cell factor (rhSCF) and recombinant human IL‐6 (rhIL‐6). In an experiment for the expression of chymase during differentiation, chymase+ cells were detected in human BM, but tryptase+ cells were not found.

Objective
The purpose of this study was to show the appearance of chymase+ cells in CD34+ cells with an origin different from MC differentiation.

Methods
CD34+ cells from human BM were sorted with anti‐CD117 monoclonal antibody (mAb), and cytospins of CD34+, CD34+CD117+, or CD34+CD117− were prepared. These cells were cultured with rhSCF+rhIL‐6 for 12 weeks. Some of the cells were subjected to either histological stain with Wright–Giemsa or immunocytochemistry with anti‐chymase mAb. Real‐time RT‐PCR was also performed to compare the transcriptional level of chymase from each cell preparation.

Results
Chymase was expressed in CD34+ cells as well as human MCs by immunocytochemistry. Substantial CD34+CD117− cells, but not CD34+CD117+ cells, were stained immunocytochemically with anti‐chymase mAb. For 1 week culture with rhSCF+rhIL‐6, no cells expressed chymase in any preparation. Real‐time RT‐PCR revealed positivity for chymase mRNA in CD34+ cells, but it reduced at 1 week of culture, and increased as cells developed into MCs. Chymase mRNA in CD34+CD117+ cells was negligible compared with that in CD34+CD117−. Tryptase mRNA was below the detectable level in CD34+ cells, and increased along with MC differentiation. After 12 weeks of culture, CD34+CD117+ developed predominantly into MCs, whereas CD34+CD117− developed into monocytes/macrophages.

Conclusion
Our findings suggested that chymase is present not only in MCs but also in CD34+CD117− BM progenitors, but that its origin is different from the MC lineage.
What impact will the immune tolerance network have on the future treatment of allergic diseases?
Authors: Saxon A.
Published: November 2004

The immune tolerance network (ITN) plans to capitalize on the current state of understanding of immunologic science to solicit, design and implement human trails designed to ‘cure’ allergic diseases. While the ITN can bring tremendous resources to bear, it is actively looking for the participation of innovative physician–scientists worldwide in order to optimize the changes of success and thereby have a major impact on the future treatment of allergic diseases.
The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation
Authors: HARBOE M , ULVUND G , VIEN L , FUNG M , MOLLNES T E
Published: November 2004

Complement activation with formation of biologically potent mediators like C5a and the terminal C5b-9 complex (TCC) contributes essentially to development of inflammation and tissue damage in a number of autoimmune and inflammatory conditions. A particular role for complement in the ischaemia/reperfusion injury of the heart, skeletal muscle, central nervous system, intestine and kidney has been suggested from animal studies. Previous experiments in C3 and C4 knockout mice suggested an important role of the classical or lectin pathway in initiation of complement activation during intestinal ischaemia/reperfusion injury while later use of factor D knockout mice showed the alternative pathway to be critically involved. We hypothesized that alternative pathway amplification might play a more critical role in classical pathway-induced C5 activation than previously recognized and used pathway-selective inhibitory mAbs to further elucidate the role of the alternative pathway. Here we demonstrate that  selective  blockade  of  the  alternative  pathway  by  neutralizing  factor  D  in  human  serum  diluted 1 : 2 with mAb 166–32 inhibited more than 80% of C5a and TCC formation induced by solid phase IgM and solid- and fluid-phase human aggregated IgG via the classical pathway. The findings emphasize the influence of alternative pathway amplification on the effect of initial classical pathway activation and the therapeutic potential of inhibiting the alternative pathway in clinical conditions with excessive and uncontrolled complement activation.
L-ficolin in children with recurrent respiratory infections
Authors: ATKINSON A P M , CEDZYNSKI M , SZEMRAJ J , ST. SWIERZKO A , BAK-ROMANISZYN L , BANASIK M , ZEMAN K , MATSUSHITA M , TURNER M L , KILPATRICK D C
Published: November 2004

The lectin pathway of complement activation is used by a collectin, mannan-binding lectin (MBL), and two ficolins, L-ficolin and H-ficolin, to opsonize microorganisms for phagocytosis. We published evidence recently that MBL insufficiency is associated with recurrent respiratory infections in childhood. We have now measured serum L-ficolin in 313 respiratory infection patients and 74 healthy control children. L-ficolin concentrations below the lower limit of the control group were found in 6% of the patients (P < 0·02) and were associated most strongly with children having co-existing atopic disorders (11%; P = 0·002). We suggest that L-ficolin may have a role in protection from microorganisms complicating allergic disease.
TSH receptor-adenovirus-induced Graves’ hyperthyroidism is attenuated in both interferon-γand interleukin-4 knockout mice; implications for the Th1/Th2 paradigm
Authors: NAGAYAMA Y , SAITOH O , MCLACHLAN S M , RAPOPORT B , KANO H , KUMAZAWA Y
Published: November 2004

The role of the Th1/Th2 balance in the pathogenesis of murine Graves’ hyperthyroidism is controversial. In BALB/c mice injected with adenovirus expressing TSH receptor (TSHR-adeno model), we found that suppression of TSHR-specific Th1 immune responses by exogenous interleukin-4 (IL-4), α-galactosylceramide or helminth (Schistosoma mansoni) infection was associated with inhibition of hyperthyroidism, indicating the critical role for Th1 cytokines. In contrast, BALB/c IL-4 knockout (KO), but not interferon-γ (IFN-γ) KO mice failed to develop Graves’ hyperthyroidism when injected with TSHR-expressing M12 B lymphoma cells (TSHR-M12 model), suggesting the importance of Th2 cytokine IL-4. To reconcile differences in these two models, we used IL-4 KO and IFN-γ KO BALB/c mice in the TSHR-adeno model. Unlike wild-type (wt) BALB/c mice in which 60% developed hyperthyroidism, only 13 and 7% of IL-4 KO and IFN-γ KO mice, respectively, became hyperthyroid. Thyroid stimulating antibodies were positive in most hyperthyroid mice. TSHR antibody titres determined by TSH binding inhibition and ELISA were comparable in all three groups. IgG1 and IgG2a TSHR antibody titres were similar in IFN-γ KO and wt mice, whereas IgG1 TSHR antibody titres and TSHR-specific splenocyte IFN-γ secretion were lower in IL-4 KO than in IFN-γ KO and wt mice, respectively. Our results clearly implicate both IFN-γ and IL-4 in development of hyperthyroidism in the TSHR-adeno model. These data, together with the previous report, also indicate different cytokine requirements in these two Graves’ models, with IFN-γ being more important in the TSHR-adeno than the TSHR-M12 model. Moreover, our previous and present observations indicate a difference in the role of exogenous versus endogenous IL-4 in TSHR-adenovirus induced Graves’ hyperthyroidism.
Antibodies cross-reacting with thyroglobulin and thyroid peroxidase are induced by immunization of rabbits with an immunogenic thyroglobulin 20mer peptide
Authors: THRASYVOULIDES A , LYMBERI P
Published: November 2004

Thyroglobulin (Tg) and thyroid peroxidase (TPO) are two major autoantigens in autoimmune thyroid diseases (AITD). Cross-reactive anti-Tg/TPO antibodies have been identified in patients with AITD and in mice immunized with Tg or TPO. In the present study, we investigated the production of anti-Tg/TPO antibodies in rabbits immunized with human Tg and with a highly immunogenic Tg peptide (namely TgP41, sequence 2651–2670 of human Tg), by noncompetitive and competitive ELISA. TgP41 was found previously to induce intramolecular epitope spreading. We found that Tg-immunized rabbits developed a serological immune response to TPO due to cross-reactivity with Tg, since serum TPO reactivity was inhibited by soluble Tg and affinity-purified anti-Tg antibodies cross-reacted with TPO. Moreover, TgP41-immunized rabbits responded to Tg and TPO. This serological response was attributed to anti-Tg/TPO antibodies, based on the observation that serum TPO reactivity was again inhibited by soluble Tg, and affinity-purified anti-Tg antibodies, induced by TgP41-immunization, cross-reacted with TPO. Purified anti-TgP41 antibodies did not react with TPO, suggesting that a putative common antigenic determinant is not included in the peptide sequence. We propose that intermolecular spreading of reactivity to TPO observed after administration of the Tg-peptide is a result of intramolecular epitope spreading to determinant(s) responsible for Tg/TPO cross-reactivity.
Agronomic factors affecting the yield and quality of forage maize in Ireland: effect of plastic film system and seeding rate
Authors: Keane G. P. , Kelly J. , Lordan S. , Kelly K.
Published: November 2004

The objectives were to compare the effects of two plastic film systems [perforated (PP) and complete‐cover (CC) systems] on the yield and quality of forage maize, and to study the effects of seeding rate on maize grown with, and without, plastic film. Between 1995 and 1998 (Experiments 1 and 2), comparisons were made of maize without plastic film systems (NP), sown through clear plastic film (PP) and covered with clear plastic film (CC). In the CC system, the plastic was removed manually from the crop. Two dates of removal (CC1 and CC2) were compared in 1995, while four removal dates (CC1, CC2, CC3 and CC4) were examined in 1996–98. In 1996–98, three sowing dates (early, mid‐April; mid, early‐May; late, mid‐May) were also examined. Four seeding rates (78 200, 93 900, 107 000 and 126 000 seeds ha−1) were examined in two experiments (Experiment 3 in 1996 and Experiment 4 in 1996–98). No plastic was used in Experiment 3, while three plastic treatments (NP, PP and CC) were examined in Experiment 4. In the CC treatment, the plastic film was removed at the six‐ to eight‐leaf stage.

In Experiment 1, the PP treatment gave lower DM yields than the NP treatment due to frost damage which killed 0·30 of the plants in the PP treatment. Plants were undamaged by frost in both CC treatments, and the CC2 treatment (plastic removal at the six‐leaf stage) gave significant increases in DM and grain yields. In Experiment 2, averaged over years and sowing dates, DM yields were significantly increased by all plastic film treatments except CC4. All plastic film treatments gave significantly earlier tassel emergence than the NP treatment, and significantly increased grain yields and contents of DM and grain. The highest yields of DM and grain were obtained from the PP system. Within the CC treatments, leaving the plastic film intact until the ten‐leaf stage (CC4) gave lower yields of DM and grain than removing the plastic film at an earlier stage. Averaged over years, the largest DM yields were obtained from the CC system with early‐sown material, while the yield differences between treatments with late‐sown crops under this system were not significant. Highest DM and grain yields were obtained with early sowing, while late sowing gave lower contents of DM and grain, and later tassel emergence.

In Experiments 3 and 4, DM and grain yields increased as seeding rate increased up to 126 000 seeds ha−1 with NP and CC plastic treatments. With the PP treatment, DM yield reached a plateau at 107 000 seeds ha−1. Seeding rate did not significantly affect DM content in either experiments but grain content declined in both experiments as seeding rate increased.
Simultaneous increase in germ cell apoptosis and oxidative stress under acute unilateral testicular ischaemia in rats
Authors: Chaki S. P. , Ghosh D. , Misro M. M.
Published: November 2004

Ischaemia induced germ cell apoptosis in rat testis was studied in detail to find out (i) spermatogenic stage or seminiferous epithelium region specific involvement of germ cells in apoptosis, (ii) preferential specificity of a particular germ cell type to become apoptotic and (iii) the ratio of live and dead testicular cells isolated in vitro after various period of ischaemic induction. Cell apoptosis, as observed in histological sections increased from 1 to 24 h of ischaemia. Apoptosis was not restricted to any specific germ cell type but was observed simultaneously in all the cell types in the initial hours (1–6 h) of ischaemia. No spermatogenic stage specific preference in apoptotic induction was also observed. However, as the duration of ischaemia progressed, the cell types observed to be most affected in number and morphology were the spermatids followed by spermatocytes. Centrally located tubules of testis were affected first than those located in the periphery. Overexpression of Bax staining was limited to few germ cell nuclei only. More than 95% of the germ cells in the control testis that earlier showed trypan blue dye exclusion were found stained after 12 h of ischaemia. Starting from early hours (1 h), lipid peroxidation rose proportionally with the duration of ischaemia while superoxide dismutase (SOD) and catalase activities were found decreased. Significant (p < 0.05) increase in the activities of glutathion‐s‐transferase and levels of hydrogen peroxide were observed after 6 h of ischaemia. These findings indicate that the physiological processes of oxidative stress have a direct linkage to the extent of germ cell apoptosis in the seminiferous epithelium.
The use of guar and xanthan gums in the production of ‘light’ low fat cakes
Authors: Zambrano Francy , Despinoy P. , Ormenese R. C. S. C. , Faria E. V.
Published: November 2004

The objective of this work was to develop low fat or light cakes by substituting the fat with either guar or xanthan gums. In order to measure the effect of this substitution, the following were evaluated: specific density of the dough, specific volume, moisture content, internal characteristics and the presence of moulds. Cakes with 25 and 50% substitution of the fat were also evaluated with respect to water activity (Aw), firmness and elasticity. The proximate composition analysis was used to determine the reductions in fat content and caloric value. Cakes with 50% substitution with guar and xanthan gums, up to 15 days storage, showed no significant difference (P < 0.05) with respect to firmness and elasticity. Therefore substitution of 50% of the normal fat content with gums allowed the production of cakes that were light with respect to their fat content. It was found that those made with xanthan gum were considered better with respect to overall appreciation and texture in the acceptability test.