bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving human capital inside the production boundary
Authors: Aulin‐Ahmavaara Pirkko
Published: May 2004

Moving human capital inside the production boundary requires human capital and its services to be treated as outputs of production processes. The primary input of labor ceases to exist, and it is necessary to redirect goods and services consumed by it as inputs in the industries that now produce human capital and its services, i.e. human time. A description of the total production system, which includes these industries, is given. This description is formalized by means of the dynamic input‐output model. The potential uses of this approach are discussed. Two well‐known approaches to include human capital in national accounts are discussed against this background. They lead to exceptionally high rates of return on inputs in human capital and, logically, also leave substantial resources available to net additions to the stocks of human capital.
Path dependence of the general price level: A value theoretic analysis
Authors: Reich Utz‐Peter
Published: May 2004

The paper examines path dependence of price indexes, a problem that has become acute after international adoption of chain indexes for price and volume changes in the SNA93. Path dependence is an old issue of index numbers, and has been in the way of using chain indexes ever since their invention. The paper accepts chaining at its start, and tries to develop a sound deflation procedure from there. In this analysis path dependence is less an issue of appropriate formalization of a given concept, the traditional approach in index number theory, but rather a problem of developing an interpretation to a given and now worldwide recommended statistical practice. The key issue is found in the fact that money is not only the standard means of payment, concerning central banks, but also the standard of value in an economy, a feature that bears directly on the compilation of price indexes and national accounts. As a result, a chained weighted index is shown to be path independent, if it is interpreted as a change not of prices, but of the unit of account in which prices are expressed.
The system of national accounts for the new economy: What should change?
Authors: Moulton Brent R.
Published: May 2004

The publication of the 1993 System of National Accounts served as a major milestone in creating international standards for compiling a fully integrated set of accounts measuring a nation's production, income, and wealth. While statistical agencies continue to make progress toward full implementation of the 1993 SNA, attention is now turning to perceived deficiencies of the system and areas for possible improvement. This paper discusses several suggestions for possible changes in the national accounts, including inclusion of multifactor productivity measures in the production account, changes to the definition of output for certain financial services, expanded coverage of intangible assets, capitalization of military equipment, inclusion of consumer durable goods in measures of saving, imputation of a rate of return to fixed assets used for nonmarket production, reconsideration of sectoral boundaries, and modification of the definition of capital transfers for capital gains taxes.
PLEASURE AS THE STANDARD OF VIRTUE IN HUME's MORAL PHILOSOPHY1
Authors: DRIVER JULIA
Published: May 2004

Abstract:  David Hume provides several accounts of moral virtue, all of which tie virtue to the experience of pleasure in the spectator. Hume believed that the appropriate pleasure for determinations of virtue was pleasure corrected by “the general point of view.” I argue that common ways of spelling this out leave the account open to the charge that it cannot account adequately for mistaken judgments of virtue. I argue that we need to see Hume as offering both a metaphysics and an epistemology of virtue, and that Hume's account of virtue can adequately account for mistakes if he is understood as offering a definition of virtue tied to pleasure, but pleasure understood externally.
The New Men's History and the Peculiar Absence of Gendered Power: Some Remedies from Early American Gender History
Authors: Ditz Toby L.
Published: May 2004

Historians with feminist commitments have expressed reservations about men's history and men's studies. This unease has existed more or less from the first appearance of men's history as a specialised area of inquiry, and shows no signs of abating. The first part of this article explores the sources of this unease. It discusses several guiding premises of men's history and shows that they tend to lead to the occlusion of men's gendered power over women. Nonetheless, the scrutiny of the gender of men is the logical outgrowth of several decades of theoretical and empirical work on gender–witness the many historians of women and gender who have recently turned their attention to the systematic study of manliness and masculinity. With the help of examples drawn from the scholarship on the history of the British colonies in America and the early United States, the second part of this article enumerates several strategies for successfully highlighting men's gendered power in histories of manliness and masculinity.
Comment
Authors: Pedersen Jean Elisabeth
Published: May 2004

This comment responds to Hibba Abugadeiri's ‘The Scientisation of Culture: Colonial Medicine's Construction of Egyptian Womanhood, 1893–1929’ and Laura Bier's ‘Modernity and the Other Woman’: Gender and Citizenship in the Egyptian Press, 1952–1970’. Both articles contribute to our understandings of the connections between constructions of gender identity, national identity, and imperial identity. After directing some questions to each author individually, this comment examines the ways in which the two articles combine to raise questions about the power of the press in an emerging public sphere, the importance of claims to modernity in assertions of national independence and the complexity of identity formation in periods of intense political change.
A Vision of Mount Holyoke in the Ottoman Balkans: American Cultural Transfer, Bulgarian Nation‐Building and Women's Educational Reform, 1858–1870
Authors: Reeves‐Ellington Barbara
Published: May 2004

American missionaries introduced a project of female educational reform among Bulgarian Orthodox Christians in their attempt to promote a Protestant reformation in the Ottoman Balkans. This case study of American‐Bulgarian interactions in the town of Eski Zaǧora (Stara Zagora) illuminates a hitherto unexplored projection of American culture abroad and highlights the connections between women's education, religion, and national identity. In the face of Ottoman secular reform and American religious reform, Bulgarian women appropriated American educational ideals to demand improved schooling for Orthodox girls in the name of national progress. Ironically, by promoting female education, missionaries ensured the failure of their Protestant reformation and inadvertently contributed to shaping a Bulgarian national discourse during a period of increasing Balkan nationalism.
(Homo)sex in the City Only? Finding Continuity and Change in the Gay Past
Authors: Healey Dan
Published: May 2004

Books reviewed in this article:

Glenn Burger and Steven F. Kruger (eds), Queering the Middle Ages

John Howard, Men Like That: A Southern Queer History

Stephen O. Murray, Homosexualities
About Understanding across Time and Space
Authors: Blom Ida
Published: May 2004

Book reviewed in this article:

Anna Lindberg, Experience and Identity: A Historical Account of Class, Caste and Gender among the Cashew Workers of Kerala, 1930–2000
The promoter of the Arabidopsis thaliana Cel1 endo‐1,4‐β glucanase gene is differentially expressed in plant feeding cells induced by root‐knot and cyst nematodes
Authors: Mitchum Melissa G. , Sukno Serenella , Wang Xiaohong , Shani Ziv , Tsabary Galit , Shoseyov Oded , Davis Eric L.
Published: May 2004

Transgenic tobacco and Arabidopsis thaliana carrying the Arabidopsis endo‐1,4‐β‐glucanase (EC 3.2.1.4) Cel1 promoter fused to the β‐glucuronidase (GUS) reporter gene were infected with the root‐knot nematode, Meloidogyne incognita, and either the tobacco cyst nematode, Globodera tabacum (tobacco), or beet cyst nematode, Heterodera schachtii (Arabidopsis). Cel1‐driven GUS expression was detected in cell elongation zones of noninfected plants and within feeding sites (giant‐cells) induced in roots of both plant hosts by M. incognita. The first detectable signs of Cel1 expression within developing giant‐cells occurred at the onset of giant‐cell formation and continued throughout the M. incognita life cycle. UidA (Gus) transcripts were detectable within giant‐cells induced in tobacco roots at 11–13 days postinoculation with M. incognita as determined by in situ mRNA hybridization. By contrast, expression of the Cel1 promoter was not detected within developing syncytia induced in tobacco or Arabidopsis roots by G. tabacum and H. schachtii, respectively, at any time point. The results demonstrate specific regulation of cell wall‐degrading enzymes that may be required for cell wall modifications during feeding cell formation by sedentary endoparasitic nematodes. Differential expression of Cel1 by cyst and root‐knot nematodes further supports underlying mechanistic differences in giant‐cell and syncytium formation.
Black currant reversion virus, a mite‐transmitted nepovirus
Authors: Susi Petri
Published: May 2004

Taxonomy:
Black currant reversion virus (BRV) is the first identified mite‐transmitted member of the genus Nepovirus (family Comoviridae). A few systematic studies have been performed to compare virus isolates from different geographical locations.

Physical properties: Purified preparations contain two closely sedimenting centrifugal components (B and M for RNA1 and RNA2, respectively) at varying ratios, and occasionally a T component (for satellite RNA). The BRV capsids have a diameter of 27 nm and they are putatively composed of 60 copies of a single species of capsid (coat) protein assembled in an icosahedral lattice. Diluted plant sap loses its infectivity within 1 day at 20 °C and in 4–8 days at 4 °C.

Hosts: The natural host range of BRV is limited; it infects black currant (Ribes nigrum L.) and some related Ribes species. The transmission of the virus is by the eriophyid gall mite of black currant (Cecidophyopsis ribis). A number of herbaceous plants can be infected experimentally. BRV is the agent of black currant reversion disease (BRD), which is economically the most significant virus disease in Ribes species. BRV and BRD occur widely in locations where black currant is cultivated commercially.
Gene expression during infection of wheat roots by the ‘take‐all’ fungus Gaeumannomyces graminis
Authors: Guilleroux M. , Osbourn A.
Published: May 2004

The infection of plants by pathogenic microbes and the subsequent establishment of disease involves substantial changes in the biochemistry and physiology of both partners. Analysis of genes that are expressed during these interactions represents a powerful strategy to obtain insights into the molecular events underlying these changes. Root diseases have considerable economic impact but have not been characterized extensively at the molecular genetic level. Here we have used two complementary approaches—suppression subtractive hybridization and expressed sequence tag analysis of an unsubtracted cDNA library—to investigate gene expression during the early stages of colonization of wheat roots by the take‐all fungus, Gaeumannomyces graminis.
Use of solid‐phase subtractive hybridization for the identification of parasitism gene candidates from the root‐knot nematode Meloidogyne incognita
Authors: Huang Guozhong , Dong Ruihua , Maier Tom , Allen Rex , Davis Eric L. , Baum Thomas J. , Hussey Richard S.
Published: May 2004

A solid‐phase subtractive strategy was used to clone parasitism gene candidates (PGCs) expressed in the oesophageal gland cells of Meloidogyne incognita. Nematode intestinal first‐strand cDNA was synthesized directly on magnetic beads and used to enrich for gland‐specific sequences by high stringency hybridization to gland‐cell mRNA. A gland‐specific cDNA library was created from the nonhybridizing gland‐cell mRNA by long‐distance reverse transcription polymerase chain reaction. Subtraction of the gland cDNA library (1000 clones) with previously cloned M. incognita parasitism genes removed 89 cDNA clones and promoted efficient identification of new PGCs. Sequencing of 711 cDNA clones from the subtracted library revealed that deduced protein sequences of 67 cDNAs were preceded by a signal peptide for secretion, a key criterion for parasitism genes. In situ hybridization with probes from the cDNA clones encoding signal peptides showed that seven cDNA clones were specifically expressed in the subventral gland cells and four in the dorsal gland cell of M. incognita. BLASTP analyses revealed the predicted proteins of five cDNAs to be novel sequences. The six PGCs with similarities to known proteins included a pectate lyase, three beta‐1,4‐endoglucanases and two chorismate mutases. This subtractive protocol provides an efficient and reliable approach for identifying PGCs encoding oesophageal gland cell secretory proteins that may have a role in M. incognita parasitism of plants.
The Uromyces fabae UfAAT3 gene encodes a general amino acid permease that prefers uptake of in planta scarce amino acids
Authors: STRUCK CHRISTINE , MUELLER ELENA , MARTIN HOLGER , LOHAUS GERTRUD
Published: May 2004

The obligately biotrophic rust fungi are dependent on nutrient supply from their host plants. A cDNA library of infection structures of the rust fungus Uromyces fabae was used to identify a gene (UfAAT3) that encodes a protein with a high degree of sequence similarity to fungal amino acid permeases. The expression profile revealed by RT‐PCR shows an up‐regulation very early during rust development, with the highest level in haustoria and infected leaves. Heterologous expression of UfAAT3p in Xenopus oocytes revealed an amino acid permease energized by co‐transport with protons and exhibiting a broad substrate specificity. Compared to the previously described U. fabae amino acid transporter (AAT1), which represented the highest transport activities for lysine and histidine, electrophysiological measurements with cRNA of UfAAT3‐injected oocytes showed substrate preferences for leucine and the sulphur containing amino acids methionine and cysteine. The unique contribution of the amino acid permeases and their substrate affinities might be connected with the availability of amino acids in the leaf tissue. Thus, in order to compare the substrate profiles of AAT1p and UfAAT3p with the natural environment of U. fabae we analysed the amino acid concentration in the apoplastic space, in addition to that in extracts of Vicia faba leaves. The predominant free amino acids were asparagine, alanine, glutamine and glutamate. However, most amino acids were present at low concentrations (between 0.02 and 0.16 mm), including the preferred substrates of the U. fabae amino acid permeases AAT1p and UfAAT3p.
Awake craniotomy for glioblastoma in a 9‐year‐old child
Authors: Klimek M. , Verbrugge S. J. C. , Roubos S. , van der Most E. , Vincent A. J. , Klein J.
Published: May 2004

We report the pre‐operative preparation and anaesthetic management for resection of an intracerebral tumour during awake craniotomy in a 9‐year‐old boy. We believe this is the youngest patient reported to have undergone this procedure. The challenges of sedation and psychological care throughout the procedure are discussed. We conclude that the procedure can be performed safely and that it seems unacceptable to uphold an age restriction. We believe that it is the individual level of development of the child that determines suitability for this type of surgery.
Production of compound A and carbon monoxide in circle systems: an in vitro comparison of two carbon dioxide absorbents*
Authors: Struys M. M. R. F. , Bouche M. P. L. A. , Rolly G. , Vandevivere Y. D. I. , Dyzers D. , Goeteyn W. , Versichelen L. F. M. , Van Bocxlaer J. F. P. , Mortier E. P.
Published: May 2004

Two new generation carbon dioxide absorbents, DrägerSorb® Free and Amsorb® Plus, were studied in vitro for formation of compound A or carbon monoxide, during minimal gas flow (500 ml.min−1) with sevoflurane or desflurane. Compound A was assessed by gas chromatography/mass spectrometry and carbon monoxide with continuous infrared spectrometry. Fresh and dehydrated absorbents were studied. Mean (SD) time till exhaustion (inspiratory carbon dioxide concentration ≥ 1 kPa) with fresh absorbents was longer with DrägerSorb® Free (1233 (55) min) than with Amsorb® Plus (1025 (55) min; p < 0.01). For both absorbents, values of compound A were < 1 ppm and therefore below clinically significant levels, but were up to 0.25 ppm higher with DrägerSorb® Free than with Amsorb® Plus. Using dehydrated absorbents, values of compound A were about 50% lower than with fresh absorbents and were identical for DrägerSorb® Free and Amsorb® Plus. With dehydrated absorbents, no detectable carbon monoxide was found with desflurane.
Effect of chronic β‐blockade on peri‐operative outcome in patients undergoing non‐cardiac surgery: an analysis of observational and case control studies*
Authors: Giles J. W. , Sear J. W. , Foëx P.
Published: May 2004

Little is known about the effect of chronic β‐adrenoceptor antagonist therapy during the peri‐operative period in patients undergoing non‐cardiac surgery. We conducted a literature review to identify studies examining the relationship between chronic therapy and adverse peri‐operative outcome. Eighteen studies were identified in which it was possible to ascertain the incidence of adverse cardiac outcomes in those patients who were and were not receiving chronic β‐blocker therapy. None of the studies demonstrated a protective effect of chronic β‐blockade. The results of these studies were then combined and a cumulative odds ratio calculated for the likelihood of myocardial infarction, cardiac death and major cardiac complications. Patients receiving chronic β‐blocker therapy were more likely to suffer a myocardial infarction (p < 0.05). These findings differ from the published effects of acute β‐blockade. Reasons for this discrepancy are considered.
A prospective, randomised, single‐blind pilot study to determine the effect of anaesthetic technique on troponin T release after off‐pump coronary artery surgery
Authors: Kendall J. B. , Russell G. N. , Scawn N. D. A. , Akrofi M. , Cowan C. M. , Fox M. A.
Published: May 2004

Ischaemic damage to the myocardium inevitably occurs during coronary artery surgery. However, the extent of the damage may be influenced by the anaesthetic technique used. The most sensitive and reliable marker of myocardial damage is currently thought to be troponin T. We conducted a prospective, randomised, single‐blind pilot study to determine the baseline values of troponin T release after off‐pump coronary artery bypass surgery in 30 patients randomly allocated to receive either propofol, isoflurane or isoflurane and high thoracic epidural analgesia. All other treatment was standardised. Patients undergoing emergency surgery and those with unstable angina were excluded. Blood samples were taken at 0, 3, 6, 12, 24 and 48 h after surgery for troponin T analysis. Mean troponin T levels at 24 h were not significantly different between the groups (p = 0.41). These data allows appropriate power calculations for further, large‐scale studies to determine the anaesthetic technique that provides optimal myocardial protection.
The management of patients with morbid obesity in the anaesthetic assessment clinic
Authors: Coe A. J. , Saleh T. , Samuel T. , Edwards R.
Published: May 2004

One hundred and two patients with body mass indices of 37 kg.m−2 or greater were interviewed in an outpatient assessment clinic over an 18‐month period. All had been listed for elective surgery under general anaesthesia. All patients were given an explanation of the problems of morbid obesity in relation to anaesthesia. Three options were then offered to the patients: 1) to proceed with general anaesthesia as planned; 2) to undergo the planned procedure under some form of regional anaesthesia, or 3) to postpone surgery and attempt to lose significant amounts of weight. At this initial consultation, 24 patients chose option 1, 21 patients chose option 2, and 52 patients chose option 3. Four patients decided not to have the planned surgery. One patient decided to have his surgery performed at another hospital under general anaesthesia. Of the 52 patients who opted to lose weight, only eight succeeded in reducing their body mass index (BMI) by 3 or more during the period of the study. Of these eight, only four had reduced their BMI to below 35. In this study, an explanation of the problems of obesity in relation to anaesthesia, in advance of the date of surgery, had a significant effect on the type of anaesthesia chosen by most morbidly obese patients that were interviewed. Unfortunately, of those who decided to try and lose weight, only the occasional patient achieved significant weight loss. Although a laudable and advocated aim, optimization of patients with regard to their weight proved impractical in our study.
THIS ARTICLE HAS BEEN RETRACTED A comparison of nefopam and clonidine for the prevention of postanaesthetic shivering: A comparative, double‐blind and placebo‐controlled dose‐ranging study*
Authors: Piper S. N. , Röhm K. D. , Suttner S. W. , Maleck W. H. , Kranke P. , Boldt J.
Published: May 2004

Postanaesthetic shivering is a frequent complication following general anaesthesia. The aim of this study was to compare the effectiveness of three doses of nefopam with clonidine and placebo in the prevention of postanaesthetic shivering. We studied 371 patients undergoing abdominal or orthopaedic surgery. Patients were allocated to one of five groups: Group A (n = 73) received 0.2 mg.kg−1 nefopam, Group B (n = 75) 0.1 mg.kg−1 nefopam, Group C (n = 76) 0.05 mg.kg−1 nefopam, Group D (n = 73) 1.5 μg.kg−1 clonidine, and Group E (n = 74) saline 0.9% as placebo. We found a significant reduction in the incidence of shivering in Group A compared to Group C and clonidine as well as to the placebo group. All active treatments reduced the incidence and the severity of shivering compared to placebo. At 5 min postoperatively clonidine‐treated patients showed a significant decrease in MAP and a significantly lower Aldrete score compared to all other groups. No haemodynamic or sedative adverse events were observed in the nefopam‐treated patients. The results of our study indicate that nefopam (0.2 mg.kg−1) is superior to clonidine (1.5 μg.kg−1) in the prophylaxis of postanaesthetic shivering and not accompanied by sedative or haemodynamic side‐effects.
The use of bispectral index during a cardiopulmonary arrest: a potential predictor of cerebral perfusion
Authors: Azim N. , Wang C. Y.
Published: May 2004

A 62‐year‐old male underwent off‐pump coronary artery grafting surgery while cerebral function was monitored with bispectral index (BIS). The BIS monitoring was continued into the immediate postoperative period, during which time the patient experienced a cardiopulmonary arrest. The changes in the BIS values helped the resuscitating team in assessing the cerebral response to the cardiopulmonary resuscitation.
Accuracy of the Foldes‐Biro equation for measurement of oxygen uptake during anaesthesia: a laboratory simulation
Authors: Stuart‐Andrews C. , Peyton P. , Robinson G. , Lithgow B.
Published: May 2004

Laboratory benchtop testing was conducted of the Biro method for measurement of oxygen uptake from an anaesthetic breathing system by patients during low flow anaesthesia. A high precision flow and gas concentration measurement system was employed in conjunction with a physical gas exchange simulation model to test the theoretical basis of the method under controlled conditions. Simulated oxygen uptake values between 200 and 350 ml.min−1 were modelled. The Biro‐derived measurement of simulated O2 uptake significantly underestimated the target value (mean difference −88.5 ml.min−1, or −31.7%). The bias was directly proportional to the simulated O2 uptake. The Biro method has a systematic bias that cannot be explained by random measurement imprecision.
Anaesthetists' intentions to violate safety guidelines
Authors: Beatty P. C. W. , Beatty S. F.
Published: May 2004

The Theory of Planned Behaviour has been used to investigate the likelihood that anaesthetists will routinely perform three violations of safety guidelines. The three violations were: failing to visit patients before surgery, failure to perform pre‐anaesthetic equipment checks and the silencing of alarms during anaesthesia. These suggested violations arose from discussions with the Medical Defence Union. In forming the intention not to perform these violations, anaesthetists are most influenced by their normative beliefs about the violation, i.e. the opinion they believe a group of peers and other significant other people would hold about them performing the violation. The next most influential factor is their personal norms, i.e. beliefs that the individual has about whether the violation is really right or wrong, followed by behavioural beliefs, i.e. beliefs about the consequences of performing the violation, and control beliefs, i.e. beliefs about how much control they have over performing the violation. The results show that the more intense the anaesthetists' belief that the violations were important, the less likely they were to violate, except for the case of alarm silencing. This result suggests that there may be a basic lack of confidence in the reliability of audible alarms that undermines their utility.
Extra‐cellular matrix in vascular networks
Authors: Bou‐Gharios George , Ponticos Markella , Rajkumar Vineeth , Abraham David
Published: May 2004

Abstract.  The vascular network is a series of linked conduits of blood vessels composed of the endothelium, a monolayer of cells that adorn the vessel lumen and surrounding layer(s) of mesenchymal cells (vascular smooth muscle, pericytes and fibroblasts). In addition to providing structural support, the mesenchymal cells are essential for vessel contractility. The extracellular matrix is a major constituent of blood vessels and provides a framework in which these various cell types are attached and embedded. The composition and organization of vascular extracellular matrix is primarily controlled by the mesenchymal cells, and is also responsible for the mechanical properties of the vessel wall, forming complex networks of structural proteins which are highly regulated. The extracellular matrix also plays a central role in cellular adhesion, differentiation and proliferation. This review examines the cellular and extracellular matrix components of vessels, with specific emphasis on the regulation of collagen type I and implications in vascular disease.
Cytotoxicity of lavender oil and its major components to human skin cells
Authors: Prashar A. , Locke I. C. , Evans C. S.
Published: May 2004

Abstract.  Lavender (Lavandula angustifolia) oil, chiefly composed of linalyl acetate (51%) and linalool (35%), is considered to be one of the mildest of known plant essential oils and has a history in wound healing. Concerns are building about the potential for irritant or allergenic skin reactions with the use of lavender oil. This study has demonstrated that lavender oil is cytotoxic to human skin cells in vitro (endothelial cells and fibroblasts) at a concentration of 0.25% (v/v) in all cell types tested (HMEC‐1, HNDF and 153BR). The major components of the oil, linalyl acetate and linalool, were also assayed under similar conditions for their cytotoxicity. The activity of linalool reflected that of the whole oil, indicating that linalool may be the active component of lavender oil. Linalyl acetate cytotoxicity was higher than that of the oil itself, suggesting suppression of its activity by an unknown factor in the oil. Membrane damage is proposed as the possible mechanism of action.
The influence of antisense oligonucleotides against STAT5 on the regulation of normal haematopoiesis in a bone marrow model
Authors: Baśkiewicz‐Masiuk M. , Paczkowski M. , Machaliński B.
Published: May 2004

Abstract.  Cytokines and growth factors that take part in the regulation of haematopoietic cell development activate many signalling pathways in target cells. The STAT5 (signal transducers and activators of transcription) proteins are members of a family of signal transducers and activators of transcription that can be activated after cytokine stimulation. Their binding to promoters of different genes influences cell proliferation, differentiation and survival. It is suggested that they play an important role in haematopoiesis, however, the question of the real function of STAT5 proteins requires further examination. The aim of our study was to investigate the role of STAT5 in the proliferation and apoptosis of normal haematopoietic bone marrow cells derived from heparinized cadaveric organ donors (HCOD). We applied antisense oligodeoxynucleotides (ODNs) to block STAT5A and STAT5B at the mRNA level and the reverse transcription polymerase chain reaction method to study STAT5 mRNA expression in the cells after incubation with ODNs. Moreover, we performed Western blot analysis of the STAT5A protein after exposure to antisense STAT5A. We analysed the clonogenicity of the colony‐forming unit of granulocytes–macrophages and the burst‐forming unit of erythrocytes in methylcellulose cultures according to the type and the dose of ODNs. We also examined apoptosis induced in bone marrow mononuclear and CD34+ cells by employing annexin V staining and the TUNEL method using flow cytometry (FACScan). We found that the perturbation of STAT5 expression decreased the clonogenicity of bone marrow haematopoietic cells. However, we did not observe any significant increase in the percentage of apoptotic cells after incubation with antisense ODNs. It was concluded that the STAT5 proteins play a significant role in the proliferation of human bone marrow cells harvested from HCOD. These proteins might be critical in the regulation of haematopoiesis, especially under stress conditions.
Influence of tissue origins and external microenvironment on porcine foetal fibroblast growth, proliferative life span and genome stability
Authors: Zhu H. , Tamot B. , Quinton M. , Walton J. , Hacker R. R. , Li J.
Published: May 2004

Abstract.  One of the challenges of manipulating genes in primary cells is that the cells have a finite proliferation capacity. This, combined with the lower gene targeting efficiency of somatic cells, makes identification of targeted clones very difficult. The objective of this study was to establish a system that allows porcine foetal fibroblasts to reach their maximal proliferation capacity in vitro. The influence of fibroblast origin, stage of foetal development, cell seeding densities and concentration of foetal bovine serum (FBS) on the population doublings, the percentage of β‐galactosidase‐activity‐positive cells and the genome stability of foetal fibroblasts during in vitro culture was investigated. It was found that porcine foetal fibroblasts could be cultured for over 80 population doublings in the appropriate culture system. Fibroblasts from earlier stages of foetal development were better candidate cells than those from the later stages. Cells from the heart were more actively proliferative and more resistant to replicative senescence than those from the liver. Compared to 10% FBS content, 15% FBS provided better homeostatic support, not only to proliferative performance, but also in maintaining a normal karyotype. In addition, the proliferative life span of porcine foetal fibroblasts is also dependent on seeding density of the culture.
In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo‐controlled, crossover trial
Authors: Brown S. G. A. , Haas M. A. , Black J. A. , Parameswaran A. , Woods G. M. , Heddle R. J.
Published: May 2004

Background
In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful.

Objective
We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy.

Methods
During a double‐blind randomized placebo‐controlled crossover trial of Myrmecia pilosula ant VIT the following venom‐specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL‐4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry.

Results
Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL‐4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom‐induced leucocyte IL‐4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected.

Conclusion
The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre‐incubation with IL‐3. None of the tests evaluated appear to be reliable markers of successful VIT.
Syndecan‐4‐dependent migration of human eosinophils
Authors: Feistritzer C. , Kaneider N. C. , Sturn D. H. , Wiedermann C. J.
Published: May 2004

Background
Heparan sulphate proteoglycans (HSPGs) are important participants in cell surface signalling and critical in controlling cell behaviour. They modulate inflammatory cell maturation and activation, leucocyte rolling, adhesion to endothelium as well as extravasation and chemotaxis. Whether eosinophil's function is affected has not yet been reported.

Objective
We investigated the effects of transgenic, recombinant anti‐thrombin III and Kybernin P®, an anti‐thrombin III concentrate, as HSPG ligands on spontaneous and chemokine‐triggered migration of normal eosinophils from human peripheral blood in modified Boyden chamber micropore filter assays.

Methods
Eosinophils from human peripheral blood were purified using magnetic antibody cell sorting. The signalling mechanisms required for anti‐thrombin‐dependent migration were studied using signalling enzyme blockers. Expression of HSPG core protein mRNA was studied by PCR.

Results
Pre‐treatment of eosinophils with anti‐thrombin III inhibited chemotaxis toward optimal concentrations of eotaxin or RANTES (regulated upon activation normal T cell expressed and activated). In the absence of the chemokines, direct exposure to gradients of anti‐thrombin III stimulated eosinophil migration. The effects of anti‐thrombin III were abolished by pre‐treating cells with heparinase‐1, chondroitinase, sodium chlorate and anti‐syndecan‐4 antibodies. Syndecan‐4 gene expression in eosinophils was confirmed in PCR. In the presence of pentasaccharide, anti‐thrombin III lost its effect on the cells. Functional responses were also abrogated by inhibition of protein kinase C, phosphatidylinositol 3‐kinase and phosphodiesterase.

Conclusion
Data indicate that anti‐thrombin III affects eosinophil motility via the effects of its heparin‐binding site on cell surface syndecan‐4. Ligation of syndecan‐4 with anti‐thrombin III induces eosinophil migration and deactivates motility toward chemokines. These observations suggest that syndecan‐4‐dependent signalling may control eosinophil locomotion.
Effect of Mycobacterium tuberculosis chaperonins on bronchial eosinophilia and hyper‐responsiveness in a murine model of allergic inflammation
Authors: Riffo‐Vasquez Y. , Spina D. , Page C. , Tormay P. , Singh M. , Henderson B. , Coates A.
Published: May 2004

Background
Epidemiological evidence suggests that infection with Mycobacterium tuberculosis protects children against asthma. Several laboratories have shown that, in mouse models of allergic inflammation, administration of the whole live tuberculosis vaccine, Mycobacterium bovis bacillus Calmette–Guerin (BCG), prevents ovalbumin (OVA)‐induced pulmonary eosinophilia.

Objective
The aim of this study was to characterize specific M. tuberculosis molecules that are known to modulate immune responses to see if they affected pulmonary eosinophilia and bronchial hyper‐responsiveness.

Methods
C57Bl/6 mice were sensitized to OVA on days 0 and 7 and subsequently challenged with OVA on day 14 over a 3‐day period. Pulmonary eosinophilia and bronchial hyper‐responsiveness were measured 24 h following the last antigen challenge. In some groups, mice were pre‐treated with M. tuberculosis or M. tuberculosis chaperonins (Cpns)60.1, 60.2 and 10, and the effect of this treatment on the allergic inflammatory response to aerosolized OVA was established.

Results
We show that M. tuberculosis Cpns inhibit allergen‐induced pulmonary eosinophilia in the mouse. Of the three Cpns produced by M. tuberculosis, Cpn60.1, Cpn10 and Cpn60.2, the first two are effective in preventing eosinophilia when administered by the intra‐tracheal route. Furthermore, the increase in airways sensitivity to inhaled methacholine following OVA challenge of immunized mice was suppressed following treatment with Cpn60.1. The allergic inflammatory response was also characterized by an increase in Th2 cytokines IL‐4 and IL‐5 in bronchoalveolar lavage fluid, which was also suppressed following treatment with Cpn60.1.

Conclusion
These data show that bacterial Cpns can suppress eosinophil recruitment and bronchial hyper‐responsiveness in a murine model of allergic inflammation.
Human leucocyte antigen polymorphisms in nut‐allergic patients in South Wales
Authors: Hand S. , Darke C. , Thompson J. , Stingl C. , Rolf S. , Jones K. P. , Davies B. H.
Published: May 2004

Background
Peanuts and tree nuts are among the most common foods provoking severe allergic reactions including fatal anaphylaxis. However, little is known of the underlying genetic and immunological mechanisms involved.

Objective
Based on findings in other allergic diseases, we have investigated whether specific human leucocyte antigens (HLA) are associated with nut allergy.

Method
Eighty‐four patients presenting at the allergy clinic with symptoms of nut allergy were typed for the HLA Class I (HLA‐A and B) and Class II (HLA‐DRB1 and DQB1) loci by PCR using sequence‐specific primers. Carriage frequencies were compared with 82 atopic non‐nut‐allergic subjects and 1798 random blood donors.

Results
The frequency of HLA‐B*07 (28.57%) and DRB1*11 (15.48%) was increased in the nut‐allergic patients compared to the atopic controls (12.20% and 3.66%, respectively) but not when compared to the blood donors (28.86% and 10.12%). DRB1*13 and DQB1*06 were both increased in frequency in the nut allergy patients over both the atopic and blood donor controls. However, none of these increased frequencies were significant when corrected for the number of comparisons undertaken.

Conclusion
At HLA ‘2‐digit resolution’ and with undifferentiated patients with nut allergy, there are no major disturbances in the frequency of HLA‐A, B, DRB1 or DQB1 types. However, the difference in frequency of HLA‐DRB1*11 between the nut allergy patients and the atopic controls merits further investigation as this may represent an important phenotypic relationship.
Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma
Authors: Jongepier H. , Boezen H. M. , Dijkstra A. , Howard T. D. , Vonk J. M. , Koppelman G. H. , Zheng S. L. , Meyers D. A. , Bleecker E. R. , Postma D. S.
Published: May 2004

Background
Asthma is a genetically complex disease characterized by respiratory symptoms, intermittent airway obstruction and airway hyper‐responsiveness due to airway inflammation and remodelling. The ADAM33 gene is associated with asthma and airway hyper‐responsiveness and is postulated as a gene for airway remodelling.

Objective
To investigate whether polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in patients with asthma.

Methods
In a cohort of 200 asthma patients followed over 20 years, eight single nucleotide polymorphisms of the ADAM33 gene were analysed to estimate their effect on annual FEV1 decline.

Results
The rare allele of the S_2 polymorphism was significantly associated with excess decline in FEV1 (P<0.05).

Conclusion
These findings suggest that a variant in ADAM33 is not only important in the development of asthma but also in disease progression, possibly related to enhanced airway remodelling.
Efficacy of birch‐pollen immunotherapy on cross‐reactive food allergy confirmed by skin tests and double‐blind food challenges
Authors: Bolhaar S. T. H. P. , Tiemessen M. M. , Zuidmeer L. , Van Leeuwen A. , Hoffmann‐Sommergruber K. , Bruijnzeel‐Koomen C. A. F. M. , Taams L. S. , Knol E. F. , Van Hoffen E. , Van Ree R. , Knulst A. C.
Published: May 2004

Background
The effect of birch‐pollen immunotherapy (IT) on cross‐reactive food allergies is controversial.

Objective
The aim of this study was to investigate the effect of birch‐pollen IT on apple allergy and to evaluate recombinant allergens and double‐blind placebo‐controlled food challenges (DBPCFCs) as monitoring tools.

Methods
Twenty‐five adult birch‐pollen‐ and apple‐allergic patients were randomly divided into two groups, either receiving birch‐pollen IT or symptomatic drugs only. IgE and IgG4 antibodies against birch pollen, apple, natural Bet v 1 and Mal d 1 were measured. In addition, skin prick tests (SPT) were performed using recombinant Bet v 1 (rBet v 1) and Mal d 1 (rMal d 1). Clinical outcome was evaluated by DBPCFC. CD4+CD25+ regulatory T cells (Tregs) were isolated from peripheral blood and tested in functional assays.

Results
Birch‐pollen IT resulted in a significant decrease of SPT reactivity for rBet v 1 (30‐fold) and rMal d 1 (10‐fold) already after 3 months. IgG4 antibodies were potently induced against Bet v 1, displaying cross‐reactivity to Mal d 1. Visual analogue scale scores decreased >10‐fold in 9/13 patients of the IT group, with three patients converting to negative. In the control group, no decrease was observed. Birch‐pollen IT did not lead to detectable changes in the number or function of the CD4+CD25+ Tregs.

Conclusions
This trial supports the claims that birch‐pollen IT also decreases allergy to foods containing Bet v 1‐homologous allergens. Recombinant allergens and DBPCFCs have proven to be useful tools for monitoring the effect of birch‐pollen IT on linked food allergies.
Double‐stranded RNA activates RANTES gene transcription through co‐operation of nuclear factor‐κB and interferon regulatory factors in human airway epithelial cells
Authors: Ieki K. , Matsukura S. , Kokubu F. , Kimura T. , Kuga H. , Kawaguchi M. , Odaka M. , Suzuki S. , Watanabe S. , Takeuchi H. , Schleimer R. P. , Adachi M.
Published: May 2004

Background
Regulated on activation, normal T cells expressed and secreted (RANTES) is a member of the CC chemokine family and contributes to viral‐induced airway inflammation including exacerbations of asthma. Double‐stranded RNA (dsRNA) is known to be synthesized during replication of many viruses and a ligand of Toll‐like receptor 3. We hypothesized that dsRNA may mimic viral infection and induce RANTES expression in airway epithelial cells.

Objective
We first confirmed that dsRNA up‐regulated RANTES mRNA and protein synthesis in the airway epithelial cells. We next focused our studies on the transcriptional regulation of RANTES.

Methods
Airway epithelial cell line BEAS‐2B and normal human bronchial epithelial cells were used in vitro study. Levels of RANTES mRNA and protein expression were determined with RT‐PCR and ELISA. Mechanisms of transcriptional regulation were assessed by electrophoretic mobility shift assay and dual luciferase assay using RANTES promoter‐luciferase reporter plasmids.

Results
Activation of nuclear factor‐κB (NF‐κB) was confirmed by nuclear protein binding to a DNA probe derived from the RANTES promoter. Activity of the RANTES promoter was increased by dsRNA. The stimulation with dsRNA was partially inhibited in plasmids mutated at either of the binding sites for NF‐κB or IFN regulatory factors (IRFs). When both sites were mutated, the activation was totally abrogated.

Conclusion
These results imply that dsRNA activates NF‐κB and IRFs and these transcription factors activate transcription of the RANTES promoter and its protein expression in airway epithelial cells.
Prevalence and associated factors of atopic dermatitis symptoms in rural and urban Ethiopia
Authors: Yemaneberhan H. , Flohr C. , Lewis S. A. , Bekele Z. , Parry E. , Williams H. C. , Britton J. , Venn A.
Published: May 2004

Background
Allergic diseases, including atopic dermatitis (AD), are increasingly becoming a clinical problem in developing countries.

Objective
We investigated the prevalence of AD symptoms and the effects of potential environmental aetiologies in rural and urban areas of Jimma in southwestern Ethiopia.

Methods
Information on allergic disease symptoms and lifestyle factors was gathered in an interviewer‐led cross‐sectional questionnaire‐based population survey of 9844 urban and 3032 rural participants of all ages. A one‐in‐four subsample underwent skin prick testing for hypersensitivity to Dermatophagoides pteronyssinus, mixed threshings, and aspergillus.

Results
Around 95% of those eligible took part in the survey. Lifetime cumulative prevalence of AD symptoms was generally low with an overall prevalence of 1.2%, but was higher in the urban (1.5%) than in the rural area (0.3%; odds ratio (OR)=4.45 [95% CI 2.34–8.47]). AD symptoms were strongly associated with wheeze (adjusted OR=22.03 [15.45–31.42]) and rhinitis symptoms (61.94 [42.66–89.95]). Of several environmental exposures assessed, residence in a house made of brick (rather than mud) walls with wooden (rather than clay) floor, exposure to cigarette smoke as a child, having lived outside of Jimma in the past, and being of the Tigrean ethnic group were associated with an increased risk of AD symptoms.

Conclusion
Although the overall prevalence of AD symptoms was low in this Ethiopian population, a marked urban–rural gradient was evident. Lifestyle factors linked to urbanization were associated with an increased risk of AD symptoms.
Genetic predisposition to wheeze following respiratory syncytial virus bronchiolitis
Authors: Goetghebuer T. , Isles K. , Moore C. , Thomson A. , Kwiatkowski D. , Hull J.
Published: May 2004

Background
The nature of the association between severe respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing remains unknown. In a previous study, we showed that genetic variation in the IL‐8‐promoter region is associated with susceptibility to severe bronchiolitis.

Objective
The purpose of this study was to assess the association between wheezing post‐bronchiolitis and the genetic variant of IL‐8 gene.

Methods
We collected data from 134 children who had suffered from bronchiolitis, enrolled in our previous study. The occurrence of wheezing post‐bronchiolitis was recorded from a questionnaire sent by post. The association between the genotype and wheezing phenotype was assessed by family‐based and case–control approaches.

Results
Family‐based association showed that the IL‐8 variant was transmitted significantly more often than expected in the children who wheezed after the episode of bronchiolitis (transmission=56%, P=0.02). This effect was not observed in the group of children who had bronchiolitis but did not go on to wheeze. Moreover, the variant was significantly more frequent in post‐bronchiolitis wheezers compared with the general population (odds ratio=1.6, 95% confidence interval 1.0–2.6).

Conclusion
These preliminary results suggest that there is a genetic predisposition to wheeze following severe RSV bronchiolitis.