bluuebunny/crossref_metadata_2025 huggingface dataset:
An expanding family of archaeal transcriptional activators
Authors: Ouhammouch Mohamed , Geiduschek E. Peter
Published: October 2005

Transcriptional regulation in the archaea involves a mosaic of DNA-binding proteins frequently (although not exclusively) of bacterial type, modulating a eukaryal-type core transcription apparatus.
Methanocaldococcus jannaschii
(
Mja
) Ptr2, a homologue of the Lrp/AsnC family of bacterial transcription regulators that are among the most widely disseminated archaeal DNA-binding proteins, has been shown to activate transcription by its conjugate hyperthermophilic RNA polymerase. Here, two
in vitro
systems have been exploited to show that Ptr2 and a Lrp homologue from the thermophile
Methanothermococcus thermolithotrophicus
(
Mth
) activate transcription over a ≈40°C range, in conjunction with their cognate TATA-binding proteins (TBPs) and with heterologous TBPs. A closely related homologue from the mesophile
Methanococcus maripaludis
(
Mma
) is nearly inert as a transcriptional activator, but a cluster of mutations that converts a surface patch of
Mma
Lrp to identity with Ptr2 confers transcriptional activity.
Mja
,
Mth
, and
Mma
TBPs are interchangeable for basal transcription, but their ability to support Lrp-mediated transcriptional activation varies widely, with
Mja
TBP the most active and
Mth
TBP the least active partner. The implications of this finding for understanding the roles of TBP paralogues in supporting the gene-regulatory repertoires of archaeal genomes are briefly noted.
Recombination protein Tid1p controls resolution of cohesin-dependent linkages in meiosis in Saccharomyces cerevisiae
Authors: Kateneva Anna V. , Konovchenko Anton A. , Guacci Vincent , Dresser Michael E.
Published: October 2005

Sister chromatid cohesion and interhomologue recombination are coordinated to promote the segregation of homologous chromosomes instead of sister chromatids at the first meiotic division. During meiotic prophase in Saccharomyces cerevisiae, the meiosis-specific cohesin Rec8p localizes along chromosome axes and mediates most of the cohesion. The mitotic cohesin Mcd1p/Scc1p localizes to discrete spots along chromosome arms, and its function is not clear. In cells lacking Tid1p, which is a member of the SWI2/SNF2 family of helicase-like proteins that are involved in chromatin remodeling, Mcd1p and Rec8p persist abnormally through both meiotic divisions, and chromosome segregation fails in the majority of cells. Genetic results indicate that the primary defect in these cells is a failure to resolve Mcd1p-mediated connections. Tid1p interacts with recombination enzymes Dmc1p and Rad51p and has an established role in recombination repair. We propose that Tid1p remodels Mcd1p-mediated cohesion early in meiotic prophase to facilitate interhomologue recombination and the subsequent segregation of homologous chromosomes.
Defining the Retinoid Binding Site in the Rod Cyclic Nucleotide-gated Channel
Authors: Horrigan Diana M. , Tetreault Michelle L. , Tsomaia Natia , Vasileiou Chrysoula , Borhan Babak , Mierke Dale F. , Crouch Rosalie K. , Zimmerman Anita L.
Published: October 2005

Rod vision is initiated when 11-cis-retinal, bound within rhodopsin, absorbs a photon and isomerizes to all-trans-retinal (ATR). This triggers an enzyme cascade that lowers cGMP, thereby closing cyclic nucleotide-gated (CNG) channels. ATR then dissociates from rhodopsin, with bright light releasing millimolar levels of ATR. We have recently shown that ATR is a potent closed-state inhibitor of the rod CNG channel, and that it requires access to the cytosolic face of the channel (McCabe, S.L., D.M. Pelosi, M. Tetreault, A. Miri, W. Nguitragool, P. Kovithvathanaphong, R. Mahajan, and A.L. Zimmerman. 2004. J. Gen. Physiol. 123:521–531). However, the details of the interaction between the channel and ATR have not been resolved. Here, we explore the nature of this interaction by taking advantage of specific retinoids and retinoid analogues, namely, β-ionone, all-trans-C15 aldehyde, all-trans-C17 aldehyde, all-trans-C22 aldehyde, all-trans-retinol, all-trans-retinoic acid, and all-trans-retinylidene-n-butylamine. These retinoids differ in polyene chain length, chemical functionality, and charge. Results obtained from patch clamp and NMR studies have allowed us to better define the characteristics of the site of retinoid–channel interaction. We propose that the cytoplasmic face of the channel contains a retinoid binding site. This binding site likely contains a hydrophobic region that allows the ionone ring and polyene tail to sit in an optimal position to promote interaction of the terminal functional group with residues ∼15 Å away from the ionone ring. Based on our functional data with retinoids possessing either a positive or a negative charge, we speculate that these amino acid residues may be polar and/or aromatic.
Tradition and Perspectives of Arab Herbal Medicine: A Review
Authors: Saad Bashar , Azaizeh Hassan , Said Omar
Published: October 2005

Complementary and Alternative Medicine (CAM), including herbal medicine, are popular in the general population worldwide. Parallel to the increasing interest in ‘modern’ CAM therapies and the historical importance of Arab medicine, there is also a similar trend in research activities dealing with the efficacy and safety of medicinal plants in our region. Historical and current studies and surveys indicate that the Eastern region of the Mediterranean has been distinguished throughout the generations with a rich inventory of natural medicinal herbs. It is well documented that indigenous Arab medicine has contributed greatly to the development of modern medicine in Europe and remains one of the closest forms of original European medicine. The rapid increase in consumption of herbal remedies worldwide has been stimulated by several factors, including the notion that all herbal products are safe and effective. This article presents a systematic review on traditional Arab medicine including historical background, medical innovations introduced by Arab physicians in the field of safety and efficacy of herbal medicine and a state‐of‐the‐art description of traditional Arab herbal medicine in the Mediterranean region.
Iodination of murine thyroglobulin enhances autoimmune reactivity in the NOD.H2h4 mouse
Authors: Barin J G , Talor M V , Sharma R B , Rose N R , Burek C L
Published: October 2005

Autoimmune thyroiditis in humans has been linked to excess iodine intake. A causative relationship between dietary iodine and thyroiditis has been clearly established in animal models of thyroiditis, including the NOD.H2h4 mouse strain, which develops enhanced thyroiditis spontaneously after supplementation of drinking water with sodium iodide. To assess the mechanisms by which iodine may contribute to disease pathogenesis, we have purified hypoiodinated thyroglobulin (Lo-I Tg) from the thyroids of mice fed methimazole and potassium perchlorate. This preparation contained only a trace of iodine and was poorly reactive to monoclonal antibody 42C3, which has been shown previously to distinguish hypoiodinated from normal Tg. A cloned T cell line 2D11 from a diseased NOD.H2h4 mouse proliferated in response to normal Tg, but not to Lo-I Tg. Serum antibodies from NOD.H2h4 mice with thyroiditis were poorly reactive to Lo-I Tg. To determine that these changes were due specifically to iodine content, Lo-I Tg was reiodinated in vitro. Reiodination of Lo-I Tg partially re-established the reactivity of NOD.H2h4 serum antibodies. The data demonstrate that the reactivity of thyroglobulin-specific antibodies and certain T cells are dependent on the iodine content of thyroglobulin. These findings suggest that iodine contributes to autoimmune thyroiditis in the NOD.H2h4 mouse by directly enhancing the antigenicity of thyroglobulin.
The natural killer T lymphocyte: a player in the complex regulation of autoimmune diabetes in non-obese diabetic mice
Authors: Cardell S L
Published: October 2005

Manipulation of the immune response to specifically prevent autoaggression requires an understanding of the complex interactions that occur during the pathogenesis of autoimmunity. Much attention has been paid to conventional T lymphocytes recognizing peptide antigens presented by classical major histocompatibility complex (MHC) class I and II molecules, as key players in the destructive autoreactive process. A pivotal role for different types of regulatory T lymphocytes in modulating the development of disease is also well established. Lately, CD1d-restricted natural killer T (NKT) lymphocytes have been the subject of intense investigation because of their ability to regulate a diversity of immune responses. The non-classical antigen presenting molecule CD1d presents lipids and glycolipids to this highly specialized subset of T lymphocytes found in both humans and mice. From experimental models of autoimmunity, evidence is accumulating that NKT cells can protect from disease. One of the best studied is the murine type 1 diabetes model, the non-obese diabetic (NOD) mouse. While the NKT cell population was first recognized to be deficient in NOD mice, augmenting NKT cell activity has been shown to suppress the development of autoimmune disease in this strain. The mechanism by which CD1d-restricted T cells exert this function is still described incompletely, but investigations in NOD mice are starting to unravel specific effects of NKT cell regulation. This review focuses on the role of CD1d-restricted NKT cells in the control of autoimmune diabetes.
The glycans deficiencies of macromolecular IgA1 is a contributory factor of variable pathological phenotypes of IgA nephropathy
Authors: Xu L-X , Yan Y , Zhang J-J , Zhang Y , Zhao M-H
Published: October 2005

Recent evidence has suggested that IgA1-containing macromolecules and the glycosylation of IgA1 in sera from patients with IgAN might involve the pathogenesis of IgAN. However, whether the different histological phenotypes can be attributed or not to the aberrant glycosylation of macromolecular IgA1 has not yet been elucidated. The aim of the current study is to investigate the glycosylation of IgA1 molecules in serum IgA1-containing macromolecules and their association with pathological phenotypes of IgAN. Sera was collected from 40 patients with IgAN and 20 donors. Twenty patients had mild mesangial proliferative IgAN, the remaining 20 had focal proliferative sclerosing IgAN. Polyethylene glycol 6000 was used to precipitate the macromolecules from sera of patients and controls. Biotinylated lectins were used in an enzyme-linked immunosorbent assay (ELISA) to examine different glycans on IgA1 molecules. The α2,6 sialic acid was detected by elderberry bark lectin (SNA) and the exposure of terminal galactose (Gal) and N-acetylgalactosamine (GalNAc) were detected by Arachis hypogaea (PNA) and Vilsa villosa lectin (VVL), respectively. The IgA1 glycans levels corrected by IgA1 concentrations were compared between patients and controls. Reduced terminal α2,6 sialic acid of IgA1 (79·89 ± 25·17 versus 62·12 ± 24·50, P = 0·034) was demonstrated only in precipitates from sera of patients with focal proliferative sclerosing IgAN, compared with those from controls. Reduced galactosylation of IgA1 molecules in precipitates was demonstrated in patients with both mild mesangial proliferative IgAN and focal proliferative sclerosing IgAN compared with normal controls (24·52 ± 18·71 versus 76·84 ± 32·59 P = 0·000 and 33·48 ± 25·36 versus 76·84 ± 32·59 P = 0·000). However, no significant difference was found in IgA1 glycosylation in the supernatant between patients and normal controls (P > 0·05). The glycosylation deficiency of IgA1 existed only in serum IgA1-containing macromolecules of patients with IgAN, and was associated with the renal pathological phenotypes. This suggests that aberrant glycosylation of IgA1 in serum macromolecules might be a contributory factor in the pathogenesis of IgAN.
Common variable immunodeficiency and the complement system; low mannose-binding lectin levels are associated with bronchiectasis
Authors: Fevang B , Mollnes T E , Holm A M , Ueland T , Heggelund L , Damås J K , Aukrust P , Frøland S S
Published: October 2005

The importance of the innate immune system, including mannose-binding lectin and the complement system, in common variable immunodeficiency is unclear. The objective of this study was to evaluate mannose-binding lectin and the complement system in relation to clinical and immunological parameters in patients with common variable immunodeficiency. Circulating levels of mannose-binding lectin, complement components, complement activation products and functional capacity of complement pathways were correlated to clinical features within 71 patients and compared with 30 healthy controls. The main findings were; the patients had signs of increased complement activation significantly associated with signs of autoimmunity and immunological hyperactivity; there were no signs of deficiencies of the classical and alternative complement pathways in the patient group; the prevalence of lectin pathway deficiency was the same in patients and controls, but patients with increased frequency of lower respiratory tract infections or bronchiectasis had lower capacity of the lectin pathway than patients without these features (P = 0·002 and 0·004, respectively); the serum concentration of mannose-binding lectin was inversely correlated to the frequency of lower respiratory tract infections (P = 0·002) and bronchiectasis (P = 0·01). We conclude that patients with common variable immunodeficiency have no increased frequency of complement deficiencies but signs of increased complement activation. Our findings suggest that mannose-binding lectin and the lectin complement pathway may protect against lower respiratory tract infection and bronhiectasis in patients with common variable immunodeficiency.
The therapeutic dilemma: How to use tadalafil
Authors: CAROSA E. , LOMBARDO F. , MARTINI P. , BRANDETTI F. , JANNINI E. A.
Published: October 2005

Tadalafil, a type 5 phosphodiesterase inhibitor, is a new and effective therapy for erectile dysfunction. It has unique pharmacokinetic properties in its drug class, which also includes sildenafil and vardenafil. It is also well tolerated with few side‐effects, and can be used in difficult patients such as neuropaths or diabetics.
The andrologist from medicine of reproduction to sexual medicine: the Italian experience
Authors: LENZI A. , JANNINI E. A.
Published: October 2005

The main andrological areas of interest, male reproductive and – more recently – sexual dysfunctions are most appropriately viewed as symptoms of the couple with medical, psychological and behavioural components that cannot be treated in a mechanical, purely medicinal manner (sexual medicine). The patient and his sexual partner must be active participants in a full continuum of care (medical sexology), the new challenge for the renewed and enriched field of andrology. In this field, the cooperation between basic researchers (such as geneticists, neurophysiologists, pharmacologists, ethologists) and a wide group of clinicians (such as endocrinologists, psychologists and psycho‐sexologists, psychiatrists, urologists and gynaecologists) is of paramount importance for the andrologist at the dawn of the new field of medical sexology, which will be full of scientific gratification in the years to come.
The impotent couple: low desire
Authors: CORONA G. , PETRONE L. , MANNUCCI E. , RICCA V. , BALERCIA G. , GIOMMI R. , FORTI G. , MAGGI M.
Published: October 2005

Hypoactive sexual desire (HSD) is the deficiency of sexual fantasies and desire that should be considered as a disorder if it causes distress to the couple. In the general population, it is the most widespread sexuality‐related problem. It is generally accepted that testosterone and prolactin regulate sexual desire. We recently reported that other psychobiological factors associate with HSD in a sample of almost 500 male patients attending our Outpatient Clinic for sexual dysfunction, by using SIEDY structured interview. We now originally extend investigation to a threefold broader patient sample. Considering marital parameters, perceived partner's libido and climax, patient's partner diseases, conflictual or even prolonged couple relationship were all significantly associated with an impairment of patients’ sexual desire. Moreover, other lifestyle factors as satisfaction at work and/or domestic inhabitant relationship were significantly correlated to hypoactive sexual desire disorder (HSDD). Among hormonal parameters, severe hyperprolactinaemia (>700 mU/L), although rarely diagnosed (<2.0%), seems to play a greater role than the more common (23%) endocrine disease hypogonadism (testosterone < 12 nm) to the pathogenesis of HSD (RR = 7.5 [2.5–22.4] vs. 1.5 [1.1–1.9], respectively). Both mental disorders and use of medication interfering with sexual function were also significantly associated with HSDD, as well as depressive and anxiety symptoms. Finally, HSD was inversely correlated to sexual and masturbation frequency attempts. In conclusion, HSD is associated with several biological, psychological, and relational factors that can be simultaneously identified and quantified using the SIEDY structured interview.
Endocrine causes of erectile dysfunction
Authors: SORAN H. , WU F. C. W.
Published: October 2005

Erectile dysfunction (ED) is one of the commonest disorders of male sexual function. Penile erection depends on a complex interaction of psychological, neural, vascular and endocrine factors. Testosterone has an important role in both central and peripheral domains of this process. In this article we discuss the role of testosterone in male sexual function and endocrine causes of ED.
A turanose‐insensitive mutant suggests a role for WOX5 in auxin homeostasis in Arabidopsis thaliana
Authors: Gonzali Silvia , Novi Giacomo , Loreti Elena , Paolicchi Fabio , Poggi Alessandra , Alpi Amedeo , Perata Pierdomenico
Published: October 2005

Sugars acting as signalling molecules regulate many developmental processes in plants, including lateral and adventitious root production. Turanose, a non‐metabolizable sucrose analogue, profoundly affects the growth pattern of Arabidopsis seedlings. Turanose‐treated seedlings are characterized by a very short primary root and a short hypocotyl showing the production of adventitious roots. A turanose‐insensitive (tin) mutant was identified and characterized. Because of a T‐DNA insertion and a chromosomal translocation, tin expresses a chimeric form of WOX5, a gene known to be expressed in the root quiescent centre. The tin mutation can be complemented by overexpression of WOX5, suggesting it is a loss‐of‐function mutant. We found that WOX5 is both turanose‐ and auxin‐inducible. Moreover, turanose insensitivity is associated with altered auxin homeostasis, as demonstrated by the constitutive activation of indole acetic acid (IAA) conjugation and SUPERROOT2 expression in tin. On the basis of turanose effects on wild‐type seedlings and the tin molecular and hormonal phenotype, we propose a role for WOX5 in the root apical meristem as a negative trigger of IAA homeostatic mechanisms allowing the maintenance of a restricted area of auxin maximum, which is required for a correct root‐formation pattern.
Homologous protein import machineries in chloroplasts and cyanelles1
Authors: Steiner Jürgen M. , Yusa Fumie , Pompe Johannes A. , Löffelhardt Wolfgang
Published: October 2005

The cyanelles of the glaucocystophyte alga Cyanophora paradoxa resemble endosymbiotic cyanobacteria, especially in the presence of a peptidoglycan wall between the inner and outer envelope membranes. However, it is now clear that cyanelles are in fact primitive plastids. Phylogenetic analyses of plastid, nuclear and mitochondrial genes support a single primary endosymbiotic event. In this scenario, cyanelles and all other plastid types are derived from an ancestral photosynthetic organelle combining the high gene content of rhodoplasts and the peptidoglycan wall of cyanelles. This means that the import apparatuses of all primary plastids, i.e. those from glaucocystophytes, red algae, green algae and higher plants, should be homologous. If this is the case, then transit sequences should be similar and heterologous import experiments feasible. Thus far, heterologous in vitro import has been shown in one direction only: precursors from C. paradoxa were imported into isolated pea or spinach chloroplasts. Cyanelle transit sequences differ from chloroplast stroma targeting peptides in containing in their N‐terminal domain an invariant phenylalanine residue which is shown here to be crucial for import. In addition, we now demonstrate that heterologous precursors are readily imported into isolated cyanelles, provided that the essential phenylalanine residue is engineered into the N‐terminal part of chloroplast transit peptides. The cyanelle and likely also the rhodoplast import apparatus can be envisaged as prototypes with a single receptor/channel showing this requirement for N‐terminal phenylalanine. In chloroplasts, multiple receptors with overlapping and less stringent specificities have evolved, explaining the efficient heterologous import of native precursors from C. paradoxa.
Is early HIV testing of infants in poorly resourced prevention of mother to child transmission programmes unaffordable?
Authors: Sherman Gayle G. , Matsebula Thulani C. , Jones Stephanie A.
Published: October 2005

Objectives  Paediatric HIV infection is predominantly vertically transmitted and 90% of the global burden is carried by Sub Saharan Africa. Diagnosis of HIV infection is important to ensure access to appropriate healthcare. Prevention of mother to child transmission (PMTCT) programmes in low resource settings fail to identify HIV‐infected children because of high lost to follow‐up rates by 12 months of age when HIV testing is performed. The cost of diagnosing HIV infection earlier in infancy was measured.

Methods  A prospective, longitudinal, descriptive study was conducted in a PMTCT clinic in Johannesburg, South Africa over an 18‐month period. From a total of 300 HIV exposed infants enrolled in an infant diagnostic study, a convenience sample of 30 was enrolled in a costing sub‐study. Patient and provider costs incurred in establishing the HIV status of an exposed infant were documented to determine the societal and provider cost of performing HIV testing at 6 weeks and 12 months of age.

Results  The average societal cost of an earlier diagnosis of HIV is R158 less per patient than current practice as determined from 123 (82%) questionnaires. On average, early diagnosis would cost the provider R8 more per patient. PMTCT clinic attendance figures predict that earlier testing would increase the number of infants diagnosed by almost threefold.

Conclusions  A marginal additional investment by government to access an earlier HIV diagnosis for infants could triple the efficacy of PMTCT programmes in identifying HIV‐infected children for medical management and improved quality and quantity of life. Early diagnosis offers societal benefits that extend beyond economic savings.
Pachydermoperiostosis: an update
Authors: Castori M , Sinibaldi L , Mingarelli R , Lachman RS , Rimoin DL , Dallapiccola B
Published: October 2005

Pachydermoperiostosis (PDP) is a rare genodermatosis, characterized by pachydermia, digital clubbing, periostosis and an excess of affected males. Although an autosomal dominant model with incomplete penetrance and variable expression has been proved, both autosomal recessive and X‐linked inheritance have been suggested. However, at present, genetic heterogeneity is not fully supported. The aim of this study is to review the clinical and pedigree data of 68 published PDP families, including 204 patients. This analysis has confirmed an autosomal dominant mutation in 37 families and suggested the existence of an autosomal recessive form in the remaining families. The two forms may differ in clinical severity, intrafamilial variability and prevalence of some features. Additionally, the marked skewed sex ratio could not be easily explained by an X‐linked mutation, but alternative explanations (i.e. testosterone promoting proliferation) are discussed.
Analysis of evolutionary conservation in CD1d molecules among primates
Authors: Saito N. , Takahashi M. , Akahata W. , Ido E. , Hidaka C. , Ibuki K. , Miura T. , Hayami M. , Takahashi H.
Published: October 2005

The hereditary conservation in the genetically encoded CD1D sequences of various primates was analyzed. Genomic CD1D sequences of 17 rhesus macaques with distinct origins, eight Indian and nine Chinese, were examined and differences of only one or two nucleotides were detected and the consensus sequence of rhesus CD1D was determined. CD1D consensus sequences of three African green monkeys (AGMs) and the rhesus monkeys were then compared to study the evolutionary differences among interspecies. The CD1D consensus sequence determined from AGMs apparently differed by seven nucleotides from the rhesus consensus sequence, and nucleotide difference induced only three amino acid changes within Exon3, corresponding to the α2 domain of CD1d having a hydrophobic ligand‐binding pocket. Such changes in the α2 domain may alter the characteristics of the SIV‐derived glycolipid/lipid antigens presented by each CD1d molecule to innate natural killer T cells. In addition, the CD1D genomic sequences of three chimpanzees (chimps) were determined. To our surprise, although Exon2 and Exon3 reflecting antigen‐binding α1 and α2 domains in chimps' CD1D were identical to that in humans except one amino acid, three amino acids within Exon4, reflecting α3 domain, were distinct from humans, and one of them was identical to those in rhesus and AGM CD1D. On the basis of the findings, the evolutionary relationship of the CD1d molecules among the various primates and their HIV‐1/SIV susceptibility will be discussed.
Polymorphisms of chemokine receptors and eNOS in Brazilian patients with sickle cell disease
Authors: Vargas A. E. , Da Silva M. A. L. , Silla L. , Chies J. A. B.
Published: October 2005

Sickle cell disease (SCD) is an inherited disorder that presents extremely variable clinical manifestations. For the past few decades, it has been approached as an inflammatory disorder, and several researchers have tried to determine the factors involved in such characteristic. In order to contribute to the identification of the genetic differences underlying this phenotypic diversity in SCD, we proposed to study the distribution of polymorphic variants of the genes encoding the chemokine receptors CCR2 and CCR5, as well as three polymorphisms in the NOS3 gene, in Brazilian SCD patients. These genes are involved in the development of inflammatory immune reactions, a feature believed to be of extreme importance in SCD pathology. Our results indicate that the polymorphisms studied here are not directly associated with severe clinical manifestations in SCD patients. Nevertheless, we observed a tendency for the development of a severe clinical course in carriers of the variant alleles CCR2‐64I and CCR5delta32 and in homozygotes for the −786C variant of the NOS3 gene. Further studies should be carried out in order to assess the role of such variants in the clinical picture of SCD.
Ecological correlation among prevalence of asthma symptoms, rhinoconjunctivitis and atopic eczema with notifications of tuberculosis and measles in the Brazilian population
Authors: Solé Dirceu , Camelo‐Nunes Inês Cristina , Wandalsen Gustavo F. , Sarinho Emanuel , Sarinho Sílvia , de Britto Murilo , Rosário Nelson A. , de Freitas Souza Leda Solano , Stein Renato , Fischer Gilberto Bueno , Naspitz Charles Kirov
Published: October 2005

This study aims to assess the relationship among incidence of tuberculosis and measles, in the general population, within the year of birth and the prevalence of asthma, rhinoconjunctivitis and atopic eczema in teenagers from different Brazilian cities enrolled in the International Study of Asthma and Allergies in Childhood (ISAAC) phases I and III. Positive answers to the questions: ‘Have you had wheezing or whistling in the chest in the past 12 months?’, ‘In the past 12 months, has this nose problem been accompanied by itchy‐watery eyes?’ and ‘Has this itchy rash at any time affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes?’ identified the teenagers with asthma, rhinoconjunctivitis, and atopic eczema, respectively. The incidence of tuberculosis and measles, in the general population, observed in the year of birth of the enrolled teenagers (1981/82 and 1988/89) were obtained from governmental agencies: National Foundation of Health (FUNASA) and Brazilian Institute of Geography and Statistics (IBGE). They were compared with the prevalence of asthma, rhinoconjunctivitis and atopic eczema reported in both ISAAC phases I and III. Although we observed reduction of the incidence of tuberculosis and measles in the general population in all cities, the prevalence of asthma, rhinoconjunctivitis and atopic eczema remained stable in most of the centers. In Pernambuco and Paraná, there has been a significant increase in the prevalence of rhinoconjunctivitis. These data do not corroborate the findings of an inverse relationship between the prevalence of atopic diseases and the decreasing incidence of tuberculosis and measles.
Role of cysteinyl leukotrienes in airway inflammation and responsiveness following RSV infection in BALB/c mice
Authors: Fullmer Jason J. , Khan Amir M. , Elidemir Okan , Chiappetta Connie , Stark James M. , Colasurdo Giuseppe N.
Published: October 2005

Cysteinyl leukotrienes (CysLTs) contribute to the development of airway obstruction and inflammation in asthma; however little information is available on the role of these molecules in the pathophysiology of respiratory syncytial virus (RSV) bronchiolitis. This study was designed to evaluate the effects of RSV infection on CysLTs production in a well‐established mouse infection model. Furthermore, we assessed the effect of anti‐inflammatory agents (a leukotriene receptor antagonist, MK‐571, and dexamethasone) on the functional and immune changes induced by RSV infection. Six to 8‐wk‐old BALB/c mice were infected with human RSV (strain A2). Measurements of airway function were performed using whole body plethysmography. Lung inflammation was assessed by cell counts, measurement of cytokines and CysLTs in bronchoalveolar lavage fluid (BALF) in the absence and presence of treatment with MK‐571 or dexamethasone. RSV infection produced a marked increase in CysLTs in the BALF and lung tissue, recruitment of neutrophils and lymphocytes into the airways, increased IFN‐γ levels and airway hyperresponsiveness (AHR). Treatment with MK‐571 decreased RSV‐induced AHR without affecting the cellular and inflammatory responses to RSV. Dexamethasone decreased AHR and markedly reduced the recruitment of inflammatory cells and production of IFN‐γ. Our findings suggest CysLTs play an important role in the pathogenesis of RSV‐induced airway dysfunction. Treatment with MK‐571 decreases RSV‐induced AHR but does not appear to alter the lung inflammatory responses to RSV. In contrast, dexamethasone decreases RSV‐induced AHR but interferes with recruitment of inflammatory cells, resulting in decreased Th1 cytokines (a potentially Th2‐prone environment) in this model. These studies support recent reports on the beneficial effects of CysLT receptor antagonist in human trials and provide a model for investigating the role of CysLTs in RSV bronchiolitis.
Induced apoptosis of TH2 lymphocytes in asthmatic children treated with Dermatophagoides pteronyssinus immunotherapy
Authors: Tsai Yi‐Giien , Chien Jien‐Wen , Chen Woan‐Ling , Shieh Jeng‐Jer , Lin Ching‐Yuang
Published: October 2005

Allergen‐specific immunotherapy (IT) has been effectively used for the treatment of asthma. Allergen specific IT induced immune tolerance with induction of TH2 cells anergy remain to be clarified. The aim of this study was to evaluate whether the mite allergen Dermatophagoides pteronyssinus (Dpt) specific IT serially decreased IL‐4+/CD4+ (TH2) lymphocytes and induced apoptosis of TH2 lymphocytes in asthmatic children. Sixty Dpt‐sensitive asthmatic children were randomly assigned to a received IT and an untreated group. Dermatophagoides pteronyssinus specific IT treated patients were examined at three time points: before IT, after 6 months of an increased dose phase and with maximum tolerated doses after 1 yr. Peripheral blood mononuclear cells (PBMC) were isolated and cultured for 48 h for cellular staining with CD4+, CD45RO cell phenotypes and interleukin (IL)‐4 and interferon‐γ expression by fluorescence monoclonal antibodies. Apoptosis was measured using the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end‐labeling (TUNEL) method. A simultaneous flow cytometric study using the same permeabilized cell was examined to determine whether apoptosis occurred preferentially in TH2 lymphocytes. The data demonstrated that Dpt specific IT decreased Dpt‐specific IgE levels (p < 0.01) after 1 yr of treatment. In addition, decreased CD4+IL‐4+ TH2 cells with increased CD4+IFN‐γ+ TH1 cells were observed at 6 months and 1 yr after IT treatment (p < 0.05). At the same time, apoptosis of CD4+IL‐4+ TH2 lymphocytes in the IT group had increased after 1 yr of treatment when compared with the results before treatment (p < 0.001) and after 6 months of treatment (p = 0.046). In addition, CD45RO cells apoptosis mainly occurred after 6 months of IT treatment and after 1‐year period of IT treatment (p < 0.05). All of the data suggested that Dpt specific IT decreased Dpt specific IgE and CD4+IL‐4+ TH2 lymphocytes with induction apoptosis of CD4+IL‐4+ TH2 lymphocytes subsets serially.
Co‐administration of salbutamol and fluticasone for emergency treatment of children with moderate acute asthma*
Authors: Estrada‐Reyes Elizabeth , E. Del Río‐Navarro Blanca , Rosas‐Vargas Miguel Angel , Nava‐Ocampo Alejandro A.
Published: October 2005

This study aimed to compare the efficacy of nebulized therapy with salbutamol alone or in combination with fluticasone. In a randomized, double‐blind clinical trial, 150 children with moderate acute asthma were randomly assigned to receive by nebulizations either (i) three doses of salbutamol 30 μl/kg per dose, each dose administered every 15 min, (ii) three doses of salbutamol plus two doses of fluticasone 500 μg/dose at 15 and 30 min after first dose of salbutamol, or (iii) three doses of salbutamol/fluticasone 500 μg/dose, each combined dose administered every 15 min. Pulse oxymetry (SaO2), peak expiratory flow (PEF) and Wood et al. (Am J Dis Child, 123, 1972, 123) clinical scale were evaluated at baseline, 15, 30, 45, 60, 90 and 120 min after the first nebulization. Patients in the three groups significantly improved since 15 min after the first nebulization. We did not observe differences in the recovery of SaO2 and PEF among the three groups of treatment (p > 0.10). In group 3, children showed better clinical response at 120 min than the other two groups (p < 0.05). No significant adverse effects were observed with any treatment. To summarize, in children with acute moderate asthma, nebulized salbutamol at an accumulated dose of 90 μl/kg plus fluticasone at an accumulated dose of 1500 μg produced better clinical relief after 2 h. However, similar PEF and SaO2 responses were observed with salbutamol alone or in combination with different doses of fluticasone.
Secretory immunoglobulin A obtained from pooled human colostrum and milk for oral passive immunization
Authors: Carbonare Cristiane B. , Carbonare Solange B. , Carneiro‐Sampaio Magda M. S.
Published: October 2005

Passive immunization is useful in cases of immunodeficiencies or infectious diseases, but usually seric gammaglobulin or hyperimmune sera are administered parenterally, providing good systemic immunization, though with low protection of the mucosal surfaces. The oral administration of secretory antibodies, especially surface immunoglobulin (SIg)A, which is perfectly adapted to the mucosal environment, would therefore, be preferable. The aim of the present study was to obtain a SIgA preparation from pooled human colostrum and milk, which should maintain the essential properties of the antibodies suitable for clinical oral administration. IgA preparations were obtained from colostrum and milk pools by salt precipitation. The final products were evaluated in terms of yield and purity, as well as antibody activity to bacterial antigens and toxins and inhibitory activity of bacterial adhesion to epithelial cells. The best yield and purity were achieved when the colostrum pool was used as a source of IgA; the final product showed very few bands of protein contamination. The IgA preparations preserved the antibody reactivity against various microbial antigens, well comparable with the reactivity exhibited by the original milk and colostrum pools. SIgA preparations were able to inhibit greatly the adhesion of enteropathogenic Escherichia coli to Hep‐2 cells and the invasion of enteroinvasive E. coli. These promising results show the feasibility of obtaining SIgA suitable for oral use, which may in future be administered to immunodeficient patients with gastrointestinal manifestations, from human colostrum and milk.
Ileostomy carcinomas a review: the latent risk after colectomy for ulcerative colitis and familial adenomatous polyposis
Authors: Quah H. M. , Samad A. , Maw A.
Published: October 2005

Background  Ileostomy carcinoma after colectomy for ulcerative colitis and familial adenomatous polyposis is rare.

Methods  Forty‐three case reports from the literature and a case of ours are reviewed.

Results  The risk of malignancy following ileostomy formation appears to be increased compared to the very low incidence of primary small bowel carcinoma. Chronic physical or chemical irritation of the stoma may predispose the ileal mucosa to colonic metaplasia with subsequent adenoma formation, dysplasia and invasive malignant change. This is particularly so where ileostomies are fashioned for familial adenomatous polyposis and ulcerative colitis.

Conclusion  Routine surveillance of patients who have had an ileostomy for 15 years or longer may lead to earlier detection of this complication.
Diverticulosis of the colon is rare amongst immigrants living in the Zaanstreek region in the Netherlands
Authors: Loffeld R. J. L. F.
Published: October 2005

Background  Data on prevalence of diverticulosis related to ethnicity or race in the Western world are very sparse. A cross‐sectional study was done in patients undergoing endoscopy of the colon in order to assess the prevalence of diverticulosis and relate the presence to ethnicity.

Methods  An analysis was undertaken of the endoscopy reports from all consecutive patients undergoing endoscopy of the colon. As a reference group all patients in whom no abnormalities were detected were used. In the Zaanstreek region a large population of immigrants, mostly of Turkish descent, is present. These immigrants were studied separately.

Results  In a period of 12 years 3004 patients were diagnosed with diverticulosis. Of these 2975 were authentic Dutch. The remainder 29 patients were immigrants. Diverticulosis was diagnosed significantly more often in immigrant men (P < 0.0001). Immigrants with diverticulosis were significantly younger than the authentic Dutch, P < 0.001. There was no major difference in representation of immigrants with diverticular disease in different age cohorts. The reference group consisted of 3356 patients. In this group 2998 patients were authentic Dutch, while 358 patients were immigrants. There was no difference in numbers of men and women amongst the immigrants. Of the patients with a normal colon and rectum 11% is immigrant. In the group of patients with diverticulosis only 0.9% was immigrant.

Conclusion  This study clearly shows that prevalence of diverticular disease is very low in immigrants. The majority of these immigrants are of Turkish descent. In addition, the majority of immigrants with diverticulosis was male.
A characterization of anaerobic colonization and associated mucosal adaptations in the undiseased ileal pouch
Authors: Smith F. M. , Coffey J. C. , Kell M. R. , O'Sullivan M. , Redmond H. P. , Kirwan W. O.
Published: October 2005

Introduction  The resolution of pouchitis with metronidazole points to an anaerobic aetiology. Pouchitis is mainly seen in patients with ulcerative colitis pouches (UCP). We have recently found that sulphate reducing bacteria (SRB), a species of strict anaerobe, colonize UCP exclusively. Herein, we aimed to correlate levels of different bacterial species (including SRB) with mucosal inflammation and morphology.

Methods  Following ethical approval, fresh faecal samples and mucosal biopsies were taken from 9 patients with UCP and 5 patients with familial adenomatous polyposis pouches (FAPP). For the purposes of comparison, faecal samples and mucosal biopsies were also taken from the stomas of 7 of the 9 patients with UC (UCS). Colonization by four types of strict anaerobes (SRB, Clostridium perfringens, Bifidobacteria and Bacteroides) as well as by three types of facultative anaerobes (Enterococci, Coliforms and Lactobacilli) was evaluated. Inflammatory scores and mucosal morphology were assessed histologically in a blinded fashion by a pathologist.

Results  In general, strict anaerobes predominated over facultative in the UCP (P = 0.041). SRB were present in UCP exclusively. Even after exclusion of SRB from total bacterial counts, strict anaerobes still predominated. In the UCS, facultative anaerobes predominated. Strict and facultative anaerobes were present at similar levels in the FAPP. Enterococci were present at significantly reduced levels in the UCP when compared with the UCS (P = 0.031). When levels of SRB and other anaerobic species were individually correlated with mucosal inflammation and morphology, no trends were observed.

Conclusion  We have previously identified that SRB exclusively colonize UCP. In addition we have now identified a novel increase in the strict/facultative anaerobic ratio within the UCP compared to UCS. These stark differences in bacterial colonization, however, appear to have limited impact on mucosal inflammation or morphology.
Evaluation of the end colostomy complications and the risk factors influencing them in Iranian patients
Authors: Mahjoubi B. , Moghimi A. , Mirzaei R. , Bijari A.
Published: October 2005

Introduction  The aim of this study was to assess the prevalence of end colostomy complications and the evaluation of factors influencing outcome.

Patients and methods . Three hundred and thirty patients with end colostomy were studied. All patient were recalled for examination for recent complications. Early complications included stoma site pain, early dermal irritation (during the first month after surgery), mucosal bleeding, stomal prolapse and psychosocial complications. Late complications included peristomal hernia, stomal stenosis, late dermal irritation (after the first month), stomal retraction, stomal necrosis and other stoma complications (perforation, fistula etc.). Probable underlying factors were studied. To evaluate risk factors affecting complications, univariable analysis and then multivariable analysis by binary logistic regression was performed.

Results  One hundred and one (30.6%) patients had no complications and the remainder had at least one of early or late complications. Overall, psychosocial complications, 56.4%; mucosal bleeding, 34.5%; early dermal irritation, 23.5% were the most frequent complications. Peristomal hernia (11.2%) was the most common late complication. Those aged > 40 years had significant associations with psychosocial problem (OR = 2.77), mucosal haemorrhage (OR = 2.19), and early dermal irritation (OR = 3.14). The risks of peristomal hernia and early dermal irritation are greater in the patients with BMI > 25 kg/m2 (OR = 2.08 and 2.55, respectively).

Conclusion  The risk of most prevalent complications of colostomy construction increases in elder patients. The high prevalence of psychosocial and skin problems in patients with a colostomy, needs special attention especially from the viewpoint of education by trained stoma nurses and preparation of standard equipment.
Infectious Disease, Productivity, and Scale in Open and Closed Animal Production Systems
Authors: Hennessy David A. , Roosen Jutta , Jensen Helen H.
Published: October 2005

Trade in feeder animals creates externalities when animal diseases can spread beyond the purchasing farm. If growers choose between open and closed production systems, then Nash equilibrium likely involves excessive trading. While first‐best equilibrium involves market‐wide adoption of either an open‐trade or closed‐farm system, equilibrium may entail heterogeneous systems. If so, then the feeder trade should be restricted. Supply response to an increase in marginal costs may be positive. Within a farm, infectious disease risk can create decreasing returns to scale when the technology is otherwise increasing returns. Contractual procurement and damage control technologies will likely increase scale in finishing.
Spatial Modeling in Technology Adoption Decisions: The Case of Shuttle Train Elevators
Authors: Sarmiento Camilo , Wilson William W.
Published: October 2005

This article empirically models a strategic game of technology adoption of shuttle train grain elevators with information on location of the firm and its competitors. A spatial econometric model illustrates the role of spatial interdependence of rivals' decisions as well as agronomic and competitive variables on discrete adoption decisions. The analysis assesses equilibria conditions that characterize technology adoption, in this case of shuttle train adoption, and the results provide an explanation of shuttle train adoption decisions in the grain handling industry in which spatial competition is critical.
GAINING FACE OR LOSING FACE? FRAMING THE DEBATE ON FACE TRANSPLANTS
Authors: HUXTABLE RICHARD , WOODLEY JULIE
Published: October 2005

An American surgical team has announced its intention to perform the first human facial transplantation. The team has, however, invited further analysis of the ethical issues before it proceeds and in this paper we take up that challenge in seeking to frame the debate with a particular focus on the recipients of the transplant. We address seven related areas of concern and identify numerous questions that require answers or, perhaps, better answers. We start by examining the nature of the procedure and its intended benefits, why the procedure is being developed, and whether or not this should be viewed as experimental. Having concluded that this is experimental in nature, we then consider the broad question, who is the patient? Here we perceive difficulties in terms of the autonomy of the recipient, the unpredictable effects of receiving the transplant, and the role and influence of society. We conclude by asking whether the question should be ‘whether or not?’ rather than ‘when?’, particularly while the risks of losing face appear to far outweigh the likelihood of gaining face.
Exploring (and Explaining) the British Prime Minister
Authors: Heffernan Richard
Published: October 2005

Institutions cannot be understood without exploring the actors who occupy them, while actors cannot be understood without examining the institutions they inhabit. Ultimately, the actions of both institutions and actors cannot be understood separate to the political, social and economic context within which they are located. Tony Blair, rightly cited as an example of a powerful prime minister, does not have a monopoly of power, but he does have an extensive authority. The prime minister requires two things to operate effectively within Whitehall and Westminster: first, power over their parliamentary majority; and second, power within the government they lead. Because this power is contested and challenged, the age-old question, the actual degree of collegiality within government, is as central to contemporary debates about the working of the core executive as to the ancient debate about prime ministerial versus cabinet government. The prime minister is therefore best modelled as a strong, but sometimes weak, parliamentary chief executive.