bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies to amino acid 200–239 (p200) of Ro52 as serological markers for the risk of developing congenital heart block
Authors: Strandberg L , Winqvist O , Sonesson S-E , Mohseni S , Salomonsson S , Bremme K , Buyon J P , Julkunen H , Wahren-Herlenius M 
Published: October 2008

Summary
Maternal autoantibodies to the p200-epitope of Ro52 have been suggested to correlate with development of congenital heart block. The aim of the present study was to evaluate the clinical relevance and predictive value of p200-antibodies in high-risk pregnancies. Sera from 515 Finnish, Swedish and American women were included in the study. Sera originated from 202 mothers with an infant affected by second- or third-degree atrioventricular block (AVB), 177 mothers with rheumatic disease having infants with normal heart rate and female blood donors (n = 136). A novel serological assay for Ro52 p200-antibodies with intra- and inter-assay variability of 3% and 3·8% respectively was developed. Mothers of children affected by AVB II-III had significantly higher p200-antibody levels than mothers with rheumatic disease having children with normal heart rate (P &lt; 0·001). In the Swedish cohort, a distinction between foetuses with normal conduction, AVB I, AVB II and III was possible. A significant difference in anti-p200 levels between AVB I and AVB II-III groups compared with foetuses with normal conduction (P &lt; 0·05 and P &lt; 0·01) was observed. Using p200-antibodies as a second step analysis in Ro52-positive pregnancies increased the positive predictive value for foetal cardiac involvement (AVB I, II or III) from 0·39 (0·27–0·51) to 0·53 (0·37–0·68). In conclusion, Ro52 p200-antibodies may occur in women with unaffected children, but levels are significantly higher in mothers of children with congenital heart block and are suggested as a relevant marker in evaluating the risk for foetal AV block.
Lessons learnt from many years of experience using anti-D in humans for prevention of RhD immunization and haemolytic disease of the fetus and newborn
Authors: Kumpel B M 
Published: October 2008

Summary
For 40 years prophylactic anti-D has been given to D-negative women after parturition to prevent haemolytic disease of the fetus and newborn. Monoclonal or recombinant anti-D may provide alternatives to the current plasma-derived polyclonal IgG anti-D, although none of them have yet proved as effective in phase 1 clinical trials. The variation in efficacy of the antibodies may have been influenced by heterogeneity in glycosylation of anti-D produced from different cell lines. Some aspects of the conduct of the human studies, most notably the use of low doses of anti-D and target D positive red cells in vivo, may aid the design of the clinical development of other immunomodulatory drugs in order to minimize adverse effects.
Potential therapy of Fc-antigen combination-encoding DNA vaccination in mouse allergic airway inflammation
Authors: Wang Y , Qian G , Wang G , Cheng X , Bai C , Wang X 
Published: October 2008

Summary
Vaccination with allergen-encoding DNA has been proposed as having potential for allergen-specific immunotherapy. In this study, we examine the therapeutic effect of allergen-encoding DNA vaccination directly to dendritic cells (DCs) on allergen-induced allergic airway inflammation in a mouse model and explore potential mechanism. Ovalbumin (OVA)-sensitized and challenged mice were immunized with DNA vaccine and received bronchoalveolar lavage (BAL) 1 day after the last challenge, to measure BAL levels of interleukin (IL)-4, IL-5, interferon (IFN)-gamma and differential cell count. Pulmonary DCs and Spleen DCs were purified and sorted according to the expression of CD11c+CD80+ and CD11c+CD86+ co-stimulatory molecules. Our data demonstrated that DNA vaccine therapy with OVA-Fc-pcDNA3·1 significantly prevented OVA-increased levels of IL-4, IL-5 and the percentage of eosinophils and OVA-decreased level of IFN-gamma. OVA-Fc-pcDNA3·1-treated mice had less severity of airway inflammation, and lower expression of CD11c+CD80+ and CD11c+CD86+ on pulmonary DCs, as compared with animals with OVA-pcDNA3·1, pcDNA3·1 and OVA respectively. DNA vaccine encoding both Fc and OVA was shown to be more effective than DNA vaccine encoding OVA alone. Our data indicate that Fc-antigen combination-encoding DNA vaccination has better preventive effects on antigen-induced airway inflammation by regulating DCs, and may be a new alternative therapy for asthma.
Expression of inflammatory mediators in the otitis media induced by Helicobacter pylori antigen in mice
Authors: Kariya S , Okano M , Fukushima K , Nomiya S , Kataoka Y , Nomiya R , Akagi H , Nishizaki K 
Published: October 2008

Summary
Helicobacter pylori is a Gram-negative bacterium that is recognized as one of the key factors in gastric diseases such as gastritis, peptic ulcer and gastric cancer. Recent studies have shown relationships between H. pylori and extra-digestive diseases, and the presence of H. pylori in the middle ear and upper respiratory tract has been reported. However, the role of H. pylori in middle ear disease remains unclear. The present study demonstrated that H. pylori whole-cell protein directly induces macrophage migration inhibitory factor, macrophage inflammatory protein 2, interleukin 1β and tumor necrosis factor α in middle ear epithelium in mice, and severe proliferation of inflammatory cells was observed in middle ear cavity inoculated with H. pylori whole-cell protein. In addition, trans-tympanic injection of macrophage migration inhibitory factor up-regulated expression of macrophage inflammatory protein 2 in the middle ear. These findings indicate that H. pylori infection causes immunological inflammation in middle ear epithelium, and H. pylori may play a significant role in otitis media.
Generation of functionally mature dendritic cells from elutriated monocytes using polyinosinic : polycytidylic acid and soluble CD40 ligand for clinical application
Authors: Kim S , Kim H O , Kim H J , Lee K , Kim H-S 
Published: October 2008

SummaryDespite the increasing use of dendritic cell (DC) vaccination in clinical trials, optimal conditions for the generation of functionally mature DCs remain to be established. The current standard DC maturation protocol for clinical trials has been used as an inflammatory cytokine cocktail [tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and prostaglandin E2], but this cocktail induced insufficient maturation of DCs derived from elutriated monocytes when cultured in X-VIVO 15. The aim of this study was to define effective combinations of stimulators for generating functionally mature DCs from elutriated monocytes under current good manufacturing practice conditions. We compared the functional capacity of DCs in response to all possible pairwise combinations of four different classes of stimuli: TNF-α, peptidoglycan, polyinosinic : polycytidylic acid [poly(I:C)] and soluble CD40 ligand (CD40L). Maturation status of DCs stimulated with combination of four stimuli was similar to that of the cytokine cocktail as assessed by the cell surface phenotype. However, only the combination of poly(I:C) + CD40L induced complete functional activation of the whole DC population, assessing IL-12p70 production, allostimulatory activity, migratory response to CCL19 and T helper 1-polarizing capacity. Thus, the protocol based on the combination of poly(I:C) and CD40L is more effective for the induction of clinical-grade DCs from elutriated monocytes than the standard cytokine cocktail.
Substandard medicines in resource‐poor settings: a problem that can no longer be ignored
Authors: Caudron J.‐M. , Ford N. , Henkens M. , Macé C. , Kiddle‐Monroe R. , Pinel J. 
Published: October 2008

SummaryThe circulation of substandard medicines in the developing world is a serious clinical and public health concern. Problems include under or over concentration of ingredients, contamination, poor quality ingredients, poor stability and inadequate packaging. There are multiple causes. Drugs manufactured for export are not regulated to the same standard as those for domestic use, while regulatory agencies in the less‐developed world are poorly equipped to assess and address the problem. A number of recent initiatives have been established to address the problem, most notably the WHO pre‐qualification programme. However, much more action is required. Donors should encourage their partners to include more explicit quality requirements in their tender mechanisms, while purchasers should insist that producers and distributors supply drugs that comply with international quality standards. Governments in rich countries should not tolerate the export of substandard pharmaceutical products to poor countries, while developing country governments should improve their ability to detect substandard medicines.
Malaria in pregnancy in an area of stable and intense transmission: is it asymptomatic?
Authors: Tagbor Harry , Bruce Jane , Browne Edmund , Greenwood Brian , Chandramohan Daniel 
Published: October 2008

SummaryObjective  To report a study of the signs and symptoms of malarial infection during pregnancy in an area of stable and intense transmission.Methods  As part of a clinical trial, to assess the efficacy and safety of four antimalarial drug regimens in pregnant women, we collected clinical and laboratory data from 900 parasitaemic pregnant women and 223 non‐parasitaemic pregnant women who attended an antenatal clinic at a district hospital in Ghana. Frequencies of signs and symptoms were calculated and their association with the level of parasitaemia was assessed using multivariate logistic regression.Results  History of fever (7.8%vs. 44.4%; P < 0.0001), headache (12.5%vs. 43.9%; P < 0.0001), vomiting (0 vs. 11.5%; P = 0.01), malaise (1.6%vs. 31.6%; P < 0.0001) dizziness (0%vs. 23%; P < 0.0001) and fatigue (0%vs. 22.5%; P < 0.0001) was substantially higher in parasitaemic primigravidae than in aparasitaemic primigravid women. Similar differences in the distribution of the symptoms and signs were observed between parasitaemic and aparasitaemic multigravid women. The proportion of women with elevated concentrations of aspartate aminotransferase, alanine aminotransferase and total bilirubin and its fractions was also higher in parasitaemic than in non‐parasitaemic women.Conclusion  In areas of stable malarial transmission, malaria in pregnancy is often symptomatic. Although the symptoms are mostly non‐specific, careful recording of history may be useful to identify women who need a confirmatory test and an effective antimalarial treatment.
Hypothermia of newborns is associated with excess mortality in the first 2 months of life in Guinea‐Bissau, West Africa
Authors: Sodemann Morten , Nielsen Jens , Veirum Jens , Jakobsen Marianne S. , Biai Sidu , Aaby Peter 
Published: October 2008

SummaryObjective To examine the long‐term effects of neonatal hypothermia (HT) on survival.Methods Using the longitudinal community and hospital surveillance system of the Bandim Health Project, we followed children born between 1997 and 2002 at the only maternity ward in the city. All children’s axillary temperature was measured within 12 h of birth. They were followed from birth to 6 months of life through regular home visits.Results We identified 2926 live births in the study area and 177 deaths before 6 months of age. Based on mortality risk, we defined a temperature below 34.5 °C as the cut‐off point for HT. Two hundred and thirty‐eight (8%) children had HT. Controlled for birth weight, HT was associated with a nearly fivefold increase in mortality during the first 7 days of life [mortality ratio (MR) = 4.81 (2.90–8.00)] and with increased mortality from 8 to 56 days of life [MR = 2.55 (1.29–5.04)].Conclusion HT is associated with excess mortality beyond the perinatal period up to at least 2 months of age, especially among low‐birth‐weight children. Hence, failure to comply with the WHO guidelines for care of newborns in low‐income countries may have long‐term consequences for child survival which have not previously been assessed. The WHO definition of HT should be based on mortality data.
Early atopic disease and early childhood immunization – is there a link?
Authors: Grüber C. , Warner J. , Hill D. , Bauchau V. ,   the EPAAC Study Group
Published: October 2008

Background:  There are frequent concerns about early immunizations among the parents of children at heightened risk for atopy. The study assessed the effect of vaccine immunization before the first birthday on eczema severity and allergic sensitization in the second year of life.Methods:  A total of 2184 infants, aged 1–2 years, with established atopic dermatitis and a family history of allergy, from 97 study centres in 10 European countries, South Africa and Australia were included. Exposure to vaccines (diphtheria, tetanus, pertussis, polio, Haemophilus influenzae Type B, hepatitis B, mumps, measles, rubella, varicella, BCG, meningococci and pneumococci) and immunization dates were recorded from immunization cards. Immunoglobulin E (IgE) was determined by RAST and eczema severity was assessed by scoring atopic dermatitis (SCORAD).Results:  Immunization against any target was not associated with an increased risk of allergic sensitization to food or inhalant allergens. Varicella immunization (only 0.7% immunized) was inversely associated with total IgE > 30 kU/l (OR 0.27; 95% CI 0.08–0.87) and eczema severity (OR 0.34; 95% CI 0.12–0.93). Pertussis immunization (only 1.7% nonimmunized) was inversely associated with eczema severity (OR 0.30; 95% CI 0.10–0.89). Cumulative received vaccine doses were inversely associated with eczema severity (P = 0.0107). The immunization coverage of infants before and after the onset of atopic dermatitis was similar.Conclusion:  In children at heightened risk for atopy, common childhood immunization in the first year is not associated with an increased risk of more severe eczema or allergic sensitization. Parents of atopic children should be encouraged to fully immunize their children.
Clinical usefulness of microarray‐based IgE detection in children with suspected food allergy
Authors: Ott H. , Baron J. M. , Heise R. , Ocklenburg C. , Stanzel S. , Merk H.‐F. , Niggemann B. , Beyer K. 
Published: October 2008

Background:  Component‐resolved diagnostics using microarray technology has recently been introduced into clinical allergology, but its applicability in children with food allergy has hardly been investigated so far. The aim of this study was to evaluate the utility of microarray‐based IgE detection in the diagnostic workup of food allergy and to compare this new diagnostic tool with established methods of allergen‐specific IgE detection.Methods:  We investigated 130 infants and children with suspected allergy to cow’s milk (CM) or hen’s egg (HE). Serum IgE measurements, skin prick tests, allergen microarray assays and controlled oral food challenges with HE and CM were performed.Results:  We analyzed 145 oral challenges that served as reference parameters for assay performance assessment. On this basis, the panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant CM and HE proteins. Additionally, the implemented CM and HE components respectively sufficed for equivalent test performance as compared to the corresponding fluorescence enzyme immunoassay extract and skin testing. However, component‐resolved diagnostics for HE and CM allergy did not make oral food challenges superfluous. Clinical IgE decision points predicting positive oral food challenges could be calculated for both in vitro test methods.Conclusions:  Allergen microarrays provide a new tool to diagnose symptomatic CM and HE allergy. They show performance characteristics comparable to the current diagnostic tests and may be indicated in small children in whom only small blood volumes are obtainable. However, they are not capable of replacing double‐blind, placebo‐controlled food challenges in most cases.
IgE antibodies to ω‐5 gliadin associate with immediate symptoms on oral wheat challenge in Japanese children
Authors: Ito K. , Futamura M. , Borres M. P. , Takaoka Y. , Dahlstrom J. , Sakamoto T. , Tanaka A. , Kohno K. , Matsuo H. , Morita E. 
Published: October 2008

Background:  Gliadins have been implicated in immunoglobulin E (IgE)‐mediated allergy to ingested wheat and ω‐5‐gliadin is known to represent a major allergen in wheat‐dependent exercise‐induced anaphylaxis. Less known is whether ω‐5‐gliadin is a clinically relevant allergen in children with immediate allergy to ingested wheat. This study investigates whether specific IgE antibodies to ω‐5‐gliadin (sIgE‐ω‐5‐gliadin‐ab) could be used as a marker for oral wheat challenge outcome in wheat‐sensitized children. A secondary objective was to study whether the level of sIgE‐ω‐5‐gliadin was related to symptom severity in children with a positive challenge test.Methods:  Serum samples from 88 children sensitized to wheat, of whom 35 underwent wheat challenge, were collected consecutively. sIgE‐ω‐5‐gliadin‐ab was related to a physician’s diagnosis of wheat allergy and challenge symptoms.Results:  The mean concentration of sIgE‐ω‐5‐gliadin‐ab was 7.25 kUA/l in patients with wheat allergy and 1.08 kUA/l in patients with no wheat allergy (P < 0.01). sIgE‐ω‐5‐gliadin‐ab was only detected in 12 of the non‐wheat allergic children and 11 of them had a specific IgE to wheat below 1.30 kUA/l. Children reacting with severe symptoms upon challenge (n = 8) had increased levels of sIgE‐ω‐5‐gliadin‐ab compared to children with moderate, mild or no symptoms (P < 0.001).Conclusions:  The presence of sIgE‐ω‐5‐gliadin‐ab is related to the reaction level to wheat challenge outcome in wheat‐sensitized children. The sIgE‐ω‐5‐gliadin‐ab was found to be associated with a strong convincing history of wheat allergy also in those cases when oral food challenge was avoided. The sIgE‐ω‐5‐gliadin‐ab level may serve as a marker for clinical reactivity in wheat‐sensitized individuals.
Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll‐like receptors
Authors: Meiler F. , Klunker S. , Zimmermann M. , Akdis C. A. , Akdis M. 
Published: October 2008

Background:  Allergic diseases are characterized by the activation of the immune system and formation of immunoglobulin (Ig)E antibodies against normally innocuous environmental antigens, whereas IgG4 and IgA represent noninflammatory and blocking antibody isotypes. The T helper 2 (Th2) cells induce and T regulatory (Treg) cells suppress several features of allergic inflammation. Our aim was to investigate the role of allergen‐specific T regulatory type 1 (Tr1) cells and CD4+CD25+ Treg cells and toll‐like receptors (TLRs) on IgE, IgG4 and IgA production.Methods:  Germline or productive Ig‐transcripts are determined by real‐time reverse transcriptase‐polymerase chain reaction, secreted Igs are measured by enzyme‐linked immunosorbent assay and the frequency of Ig‐producing plasma cells is investigated by enzyme‐linked immunosorbent spot. Circulating CD4+CD25+ Treg cells and allergen‐specific Tr1 cells are used.Results:  Both allergen‐specific, interleukin‐10‐secreting Tr1 cells and CD4+CD25+ Treg cells from healthy individuals induced IgG4 and suppressed IgE production in peripheral blood mononuclear cells and purified B‐cell cultures. In contrast, induction of IgA production is independent of T‐cell help and the role of Tr1 or Treg cells is very limited, whereas it was highly induced by direct B‐cell activation via TLR7 and 9.Conclusions:  These data suggest that T regulatory cells may contribute to the suppression of allergic diseases by suppression of IgE and induction of IgG4, whereas IgA production is enhanced by B‐cell activation via TLR7 and TLR9.
Complementary roles for lipid and protein allergens in triggering innate and adaptive immune systems
Authors: Russano A. M. , Agea E. , Casciari C. , De Benedictis F. M. , Spinozzi F. 
Published: October 2008

Background:  Recent advances in allergy research mostly focussed on two major headings: improving protein allergen purification, which is aimed towards a better characterization of IgE‐ and T‐cell reactive epitopes, and the potential new role for unconventional innate and regulatory T cells in controlling airway inflammation. These advancements could appear to be in conflict each other, as innate T cells have a poorly‐defined antigen specificity that is often directed toward nonprotein substances, such as lipids.Method:  To reconcile these contrasting findings, the model of cypress pollinosis as paradigmatic for studying allergic diseases in adults is suggested.Results:  The biochemical characterization of major native protein allergens from undenatured pollen grain demonstrated that the most relevant substance with IgE‐binding activity is a glycohydrolase enzyme, which easily denaturizes in stored grains. Moreover, lipids from the pollen membrane are implicated in early pollen grain capture and recognition by CD1+ dendritic cells (DC) and CD1‐restricted T lymphocytes. These T cells display Th0/Th2 functional activity and are also able to produce regulatory cytokines, such as IL‐10 and TGF‐β. CD1+ immature DCs expand in the respiratory mucosa of allergic subjects and are able to process both proteins and lipids.Conclusion:  A final scenario may suggest that expansion and functional activation of CD1+ DCs is a key step for mounting a Th0/Th2‐deviated immune response, and that such innate response does not confer long‐lasting protective immunity.
Comparative assessment of the water balance and hydrology of selected Ethiopian and Kenyan Rift Lakes
Authors: Ayenew Tenalem , Becht Robert 
Published: October 2008

AbstractThe study area is part of the East African Rift system, characterized by a cluster of lakes occupying an extremely faulted rift floor with geothermal manifestations. Some of the lakes illustrated contrasting water levels and size evolution over the last few decennia, believed to have been caused by various natural and anthropogenic factors. The relative importance of these factors, however, is unknown. This study attempts to present the hydrology of the lakes in a broader context, by giving more emphasis to lake water level fluctuations and to the water balance. These factors have far‐reaching implications in regard to future management of the lake basin water. It also provides information on the relation of the groundwater with the lakes, and with the local and regional groundwater flow system from the adjacent highlands to the floor of the Rift. The methods utilized in this study include conventional hydrogeological field surveys, and hydrometeorological and data analyses, coupled with digital image processing and spatial analysis under a Geographic Information System environment. Ancillary supporting information has been obtained from environmental isotopes and hydrochemical data. The study results indicate the terminal Ethiopian lakes changed in size and water level significantly over the last half century. In contrast, the Kenyan lakes only exhibited slight changes. The lakes in both countries exhibit a striking similarity in their subsurface hydraulic connection, and are strongly governed by complex rift geological structures. Groundwater plays a vital role in the water balance of the study lakes. The study results indicate that future sustainable use of the study lakes demands that serious attention be given to the role of the groundwater component of the lake water balances.