bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of systemic immunologic changes during dose build‐up phase and early maintenance period in effective specific sublingual immunotherapy in children
Authors: Dehlink E. , Eiwegger T. , Gerstmayr M. , Kampl E. , Bohle B. , Chen K.‐W. , Vrtala S. , Urbanek R. , Szépfalusi Z. 
Published: December 2005

SummaryBackground
Sublingual immunotherapy (SLIT) has been reported to be a safe treatment for inhalant allergies in children. Yet the immunologic mechanisms resulting in clinical improvement are poorly understood.Objective
To identify early systemic immunologic changes during the first 8 weeks of clinically effective SLIT to grass pollen, tree pollen or house dust mite in paediatric patients with allergic rhinoconjunctivitis and/or asthma.Methods
Peripheral blood mononuclear cells and plasma samples of 13 children with reduced symptoms after 1 year of SLIT were obtained before therapy and at 2 and 8 weeks after the initiation of SLIT. Allergen‐specific lymphocyte proliferation assays were performed, and allergen‐induced cytokine production (IL‐2, IL‐4, IL‐10, IFN‐γ, and TGF‐β1) was measured by ELISA and flow cytometry. Allergen‐specific IgE, IgG1, IgG4, and IgA levels in plasma samples were determined in ELISA.Results
During the first 8 weeks of successful SLIT, allergen‐specific lymphoproliferation (n=13) as well as levels of allergen‐specific intracellular (n=8) and secreted cytokines (n=9) did not change significantly. In addition, no alterations in levels of allergen‐specific Igs (n=7) were observed.Conclusion
We could not find any early systemic immunologic changes during the first 8 weeks of clinically effective SLIT to inhalant allergens in paediatric patients with allergic rhinoconjunctivitis and/or asthma.
Levan (β‐2, 6‐fructan), a major fraction of fermented soybean mucilage, displays immunostimulating properties via Toll‐like receptor 4 signalling: induction of interleukin‐12 production and suppression of T‐helper type 2 response and immunoglobulin E production
Authors: Xu Q. , Yajima T. , Li W. , Saito K. , Ohshima Y. , Yoshikai Y. 
Published: December 2005

SummaryBackground
Products from the fermentation process of soybeans by Bacillus subtilis (natto) have been shown to possess anti‐tumour and immunomodulatory activities. However, the formulations previously examined were not chemically pure, and this is a major limitation for elucidation of the molecular mechanisms for their activities.Objective
In order to determine which components in soybean mucilage exert immunostimulatory activities, we examined the activities of their purified forms in vitro and in vivo in mice.Methods
B. subtilis (natto) and fractions including levan and poly‐γ‐glutamic acid (γ‐PGA) from fermented soybean mucilage were prepared. Levels of cytokine production by mouse macrophage cells after treatment with the fractions were measured by means of ELISA. In vivo effect of levan delivered intragastrically on ovalbumin (OVA)‐specific T‐helper type 2 (Th2) response with IgE production was examined in BALB/c mice that had been immunized intraperitoneally with OVA.Results
Levan but neither γ‐PGA nor killed B. subtilis (natto) was found to exert strong activity to induce production of IL‐12 p40 and TNF‐α by macrophage cell lines in vitro. Results of experiments using Toll‐like receptor (TLR) 4‐deficient mice and TLR4‐transfected human cell line indicated that TLR4 is involved in pattern recognition of levan. Oral administration of levan in vivo significantly reduced the serum levels of OVA‐specific IgE and Th2 response to OVA in mice immunized with OVA.Conclusion
Levan is an immunostimulatory moiety in products from the fermentation process of B. subtilis (natto) and may be useful for prevention of allergic disorders with IgE production.
A sensitive monoclonal antibody‐based enzyme‐linked immunosorbent assay to quantify Parietaria judaica major allergens, Par j 1 and Par j 2
Authors: Arilla M. C. , González‐Rioja R. , Ibarrola I. , Mir A. , Monteseirín J. , Conde J. , Martínez A. , Asturias J. A. 
Published: December 2005

SummaryBackground
Parietaria pollen is one of the most important causes of pollinosis in Mediterranean countries. Parietaria judaica pollen extract presents two major allergens, Par j 1 and Par j 2, that belong to the lipid transfer protein family.Objective
To develop an ELISA for quantification of both major allergens of P. judaica pollen extracts, and to assert correlation of these allergens content with the allergenic activity of extracts.Methods
Natural Par j 1–Par j 2 allergens were purified by gel filtration, ion exchange, and affinity chromatography and identified by mass spectrometry. Rabbit antisera were obtained using this protein preparation as antigen and used for immunoaffinity purification of nPar j 1–Par j 2. BALB/c mice were immunized with the immunopurified nPar j 1–Par j 2 and after fusion and screening by direct ELISA, 5D4 monoclonal antibody was selected as capture antibody to develop a quantitative two‐site ELISA. Bound proteins were detected by a biotinylated Par j 1–Par j 2‐specific polyclonal antibody.Results
The optimized ELISA was developed from 25 to 8000 pg/mL of purified Par j 1–Par j 2, and a linear portion of 200–1000 pg/mL. The intraassay and interassay coefficients of variation were lower than 7% and 14% respectively. The assay was very sensitive and specific as it had a detection limit of 25 pg/mL and did not detect reactivity with the same family plants, as Urtica. Par j 1–Par j 2 allergens content was measured in 14 P. judaica and two P. officinalis pollen extracts showing a significant correlation with their allergenic activity measured by enzyme allergosorbent test inhibition.Conclusions
The results proved the usefulness of the two‐sandwich ELISA for the standardization of Parietaria pollen extracts intended for clinical use, because of its good correlation with allergenic potency.
Neo-epitopes are required for immunogenicity of the La/SS-B nuclear antigen in the context of late apoptotic cells
Authors: Pan Z-J , Davis K , Maier S , Bachmann M P , Kim-Howard X R , Keech C , Gordon T P , McCluskey J , Farris A D 
Published: December 2005

SummaryMechanisms responsible for the induction of anti-nuclear autoantibodies (ANA) following exposure of the immune system to an excess of apoptotic cells are incompletely understood. In this study, the immunogenicity of late apoptotic cells expressing heterologous or syngeneic forms of La/SS-B was investigated following subcutaneous administration to A/J mice, a non-autoimmune strain in which the La antigenic system is well understood. Immunization of A/J mice with late apoptotic thymocytes taken from mice transgenic (Tg) for the human La (hLa) nuclear antigen resulted in the production of IgG ANA specific for human and mouse forms of La in the absence of foreign adjuvants. Preparations of phenotypically healthy cells expressing heterologous hLa were also immunogenic. However, hLa Tg late apoptotic cells accelerated and enhanced the apparent heterologous healthy cell-induced anti-La humoral response, while non-Tg late apoptotic cells did not. Subcutaneous administration of late apoptotic cells was insufficient to break existing tolerance to the hLa antigen in hLa Tg mice or to the endogenous mouse La (mLa) antigen in A/J mice immunized with syngeneic thymocytes, indicating a requirement for the presence of heterologous epitopes for anti-La ANA production. Lymph node dendritic cells (DC) but not B cells isolated from non-Tg mice injected with hLa Tg late apoptotic cells presented immunodominant T helper cell epitopes of hLa. These studies support a model in which the generation of neo-T cell epitopes is required for loss of tolerance to nuclear proteins after exposure of the healthy immune system to an excess of cells in late stages of apoptosis.
Kinetics of preβ1 HDL and αHDL in type II diabetic patients
Authors: Chétiveaux M. , Lalanne F. , Lambert G. , Zair Y. , Ouguerram K. , Krempf M. 
Published: December 2005

AbstractBackground  The aim of this study was to analyze the recycling of high density lipoprotein (HDL) in six type II diabetic patients compared with six control subjects by endogenous labelling of apolipoprotein A‐I (Apo A‐I) with stable isotope Apo A.Materials and methods  The ‐I–HDL kinetics were performed by infusion of (5·5·5‐2H3)‐leucine for 14 h. The preβ1 and αHDL were separated by gel filtration fast protein liquid chromatrography system (FPLC). Kinetics of isotopic enrichment of Apo A‐I were analyzed with a multi‐compartmental model software (SAAM II, SAAM Institute, Seattle, WA).Results  Plasma Apo A‐I concentration was decreased in patients with type II diabetes as a result of a decrease in Apo A‐I‐αHDL (P < 0·05). Diabetic patients were also characterized by an increased relative contribution of Apo A‐I in preβ1 HDL (18·3 ± 2·8% vs 11·9 ± 3·7%, P < 0·01). The synthetic rate of preβ1 HDL was slightly increased in diabetic patients compared with control (NS) and an increase of recycling rate of α to preβ1 HDL was observed (11·67 ± 3·14 d−1 vs 7·09 ± 4·51 d−1, P < 0·05). The clearance rate of Apo A‐I was higher in diabetic patients (P < 0·05 for Apo A‐I‐preβ1 HDL and P < 0·005 for Apo A‐I‐αHDL).Conclusion  This study suggests that the usual increase in preβ1 HDL in type II diabetic patients is mainly related to an increased conversion rate of α to preβ1 HDL.
Antisense c‐myc fragments induce normal differentiation cycles in HL‐60 cells
Authors: Chen J. P. , Chen L. , Leek J. , Lin C. 
Published: December 2005

AbstractBackground  We have investigated the potential for using antisense technology as a means of delivering treatment for acute myeloblastic leukaemia (FAB‐M2) by gene therapy.Materials and methods  A test recombinant adenovirus vector was constructed containing human c‐myc antisense fragments to study the effects of altering c‐myc overexpression in the human HL‐60 cell line. Control vector contained the human LacZ gene. Transfection efficiency in HL‐60 cells was determined using control vector in the presence of protamine sulphate and multiplicity of infection of 100. Morphological and mechanistic changes were assessed using immunohistochemical analysis, flow cytometry and reverse transcription‐polymerase chain reaction.Results  Transfection efficiency of control vector was 79·8% and morphological differences were observed after 72 h in culture. The rate of proliferation of HL‐60 cells infected with test vector was inhibited by 73% compared with control following 6 days in culture. Normal terminal differentiation leading to apoptosis was only evident in test vector infected cells. Peak apoptosis (34·7%) was detected at day 6 and cell cycle arrest at days 2, 4 and 6. Expression of c‐fos protein was significantly increased in test vector treated cells with a noticeable down‐regulation of c‐myc expression.Conclusions  These data suggest that transfection of a human HL‐60 cell line with vector containing c‐myc antisense fragments could inhibit proliferation, but induce differentiation and apoptosis. Thus, we believe that further study of this construct is warranted as a potential gene therapy reagent for treatment of acute myeloblastic leukaemia.
Smad3‐null mice lack interstitial cells of Cajal in the colonic wall
Authors: Vetuschi A. , Sferra R. , Latella G. , D’Angelo A. , Catitti V. , Zanninelli G. , Con Tinenza M. A. , Gaudio E. 
Published: December 2005

AbstractBackground  Transforming growth factor‐β (TGF‐β)/Smad's signalling pathway plays a pivotal role in organogenesis, oncogenesis, inflammation, repair and fibrosis. The aim of this study was to evaluate the morphology of muscle layers and the density and distribution of interstitial cells of Cajal (ICC) in the colon of Smad3 knockout mice.Materials and methods  Eighteen Smad3 wild‐type mice and 12 null mice were sacrificed at age 4 months and the colons were collected for histology (Haematoxilin‐Eosin, Masson thrichrome and Gomori silver staining), morphometry and immunohistochemistry (IHC) analysis. For IHC we used the c‐Kit, α‐smooth muscle actine (α‐SMA), vimentin, desmin and neuronal cocktail (S‐100, NSE, neurofilament 200) antibodies.Results  When sacrificed, 40% of the null mice showed different degrees of colon dilatation when compared with the wild‐type. Histological and morphometric evaluation revealed a significant reduction in muscle layer thickness of the colon in all the null mice when compared with the wild‐type. Immunohistochemistry evaluation showed a marked reduction, or even absence, of c‐Kit immunoreactivity, which identifies ICC, in the colon of all the null mice, compared with the wild‐type.Conclusions  Smad3 null mice showed a marked reduction, or even absence, of ICC in the colon together with a concomitant reduction of intestinal smooth muscle layer thickness. This data could account for the colonic dilation observed in approximately 40% of the Smad3 null mice. Alteration of intestinal smooth muscle layers and ICC could also be involved in the resistance of the Smad3 null mice to develop colonic fibrosis.
Dealing with the family: CD147 interactions with cyclophilins
Authors: Yurchenko Vyacheslav , Constant Stephanie , Bukrinsky Michael 
Published: December 2005

SummaryCD147 is a widely expressed plasma membrane protein that has been implicated in a variety of physiological and pathological activities. It is best known for its ability to function as extracellular matrix metalloproteinase inducer (hence the other name for this protein, EMMPRIN), but has also been shown to regulate lymphocyte responsiveness, monocarboxylate transporter expression and spermatogenesis. These functions reflect multiple interacting partners of CD147. Recently, interaction of CD147 with proteins of the cyclophilin family has been demonstrated and activity of CD147 as a signalling receptor to extarcellular cyclophilins A and B has been shown. Given that extracellular cyclophilins are potent chemotactic agents for various immune cells, further studies of the role of cyclophilin–CD147 interaction in inflammation followed. They demonstrated that agents targeting CD147 or cyclophilin had a significant anti‐inflammatory effect in animal models of acute or chronic lung diseases and rheumatoid arthritis. Here, we review the current knowledge about interactions between CD147 and cyclophilins.
Development of polycystic ovary syndrome: involvement of genetic and environmental factors
Authors: FRANKS STEPHEN , MCCARTHY MARK I , HARDY KATE 
Published: December 2005

SummaryWe have recently proposed that polycystic ovary syndrome (PCOS) has its origin in fetal life. This hypothesis is based on data from animal models (rhesus monkey or sheep that have been exposed prenatally to high doses of androgen) and is supported by clinical studies. It is suggested that, in human females, exposure to excess androgen, at any stage from fetal development of the ovary to the onset of puberty, leads to many of the characteristic features of PCOS, including abnormalities of luteinizing hormone secretion and insulin resistance. It is likely that, in humans with PCOS, the development of the PCOS phenotype results primarily from a genetic predisposition for the fetal ovary to hypersecrete androgen. At present, it is unclear whether the maternal environment directly influences the development of PCOS in the offspring. Maternal androgen excess is unlikely to affect the fetus, because the placenta presents an effective barrier, but metabolic disturbances during pregnancy could affect development of the syndrome in the fetus. In postnatal life, the natural history of PCOS can be further modified by factors affecting insulin secretion and/or action, most importantly, nutrition. We now have evidence for a disorder of early follicular development in the polycystic ovary that is consistent with an increased population of primordial follicles in the fetal ovary. It remains to be determined whether this phenomenon is the cause or the effect of increased exposure to androgen within the ovary. PCOS is the commonest endocrine disorder in women. It is not only a very prevalent cause of anovulatory infertility, menstrual disturbances and hirsutism, but it is also a major risk factor for the development of type 2 diabetes mellitus in later life. The aetiology of the syndrome remains uncertain but there is increasing evidence for a genetic basis. PCOS very often becomes clinically manifest during adolescence with maturation of the hypothalamic‐pituitary‐ovarian axis but the genesis of the syndrome may be during very early development – perhaps even in utero. In this review, this hypothesis is explored in the light of clinical, biochemical and genetic research.
Dispersal‐related life‐history trade‐offs in a butterfly metapopulation
Authors: HANSKI ILKKA , SAASTAMOINEN MARJO , OVASKAINEN OTSO 
Published: December 2005

SummaryRecent studies on butterflies have documented apparent evolutionary changes in dispersal rate in response to climate change and habitat change. These studies often assume a trade‐off between dispersal rate (or flight capacity) and reproduction, which is the rule in wing‐dimorphic species but might not occur equally in wing‐monomorphic species such as butterflies.To investigate the relationship between dispersal rate and fecundity in the Glanville fritillary butterflyMelitaea cinxiawe recorded lifetime individual movements, matings, ovipositions, and maximal life span in a large (32 × 26 m) population cage in the field. Experimental material was obtained from 20 newly established and 20 old local populations within a large metapopulation in the Åland Islands in Finland.Females of the Glanville fritillary from newly established populations are known to be more dispersive in the field, and in the cage they showed significantly greater mobility, mated earlier, and laid more egg clutches than females from old populations. The dispersive females from new populations exhibited no reduced lifetime fecundity in the cage, but they had a shorter maximal life span than old‐population females.These results challenge the dispersal–fecundity trade‐off for nonmigratory butterflies but instead suggest a physiological trade‐off between high metabolic performance and reduced maximal life span. High metabolic performance may explain high rates of dispersal and oviposition in early life.In fragmented landscapes, an ecological trade‐off exists between being more dispersive and hence spending more time in the landscape matrix vs. having more time for reproduction in the habitat. We estimate with a dispersal model parameterized for the Glanville fritillary that the lifetime egg production is 4% smaller on average in the more dispersive butterflies in a representative landscape, with much variation depending on landscape structure in the neighbourhood of the natal patch, from −26 to 45% in the landscape analysed in this paper.
Grasshopper ontogeny in relation to time constraints: adaptive divergence and stasis
Authors: BERNER DANIEL , BLANCKENHORN WOLF U. 
Published: December 2005

Summary

Life history theory generally predicts a trade‐off between short juvenile development and large adult size, assuming invariant growth rates within species. This pivotal assumption has been explicitly tested in few organisms.
We studied ontogeny in 13 populations of Omocestus viridulus grasshoppers under common garden conditions. High‐altitude populations, facing short growing seasons and thus seasonal time constraints, were found to grow at a similar rate to low altitude conspecifics.
Instead, high‐altitude grasshoppers evolved faster development, and the correlated change in body size led to an altitudinal size cline mediating a trade‐off with female fecundity.
An additional juvenile stage occurred in low‐ but not high‐altitude females. This difference is probably due to the evolution of lowered critical size thresholds in high‐altitude grasshoppers to accelerate development.
We found a strikingly lower growth rate in males than females that we interpret as the outcome of concurrent selection for protandry and small male size.
Within populations, large individuals developed faster than small individuals, suggesting within‐population genetic variation in growth rates.
We provide evidence that different time constraints (seasonal, protandry selection) can lead to different evolutionary responses in intrinsic growth, and that correlations among ontogenetic traits within populations cannot generally be used to predict life history adaptation among populations. Moreover, our study illustrates that comparisons of ontogenetic patterns can shed light on the developmental basis underlying phenotypic evolution.
Isolation by distance and gene flow in the Eurasian badger (Meles meles) at both a local and broad scale
Authors: POPE L. C. , DOMINGO‐ROURA X. , ERVEN K. , BURKE T. 
Published: December 2005

AbstractEurasian badgers,Meles meles, have been shown to possess limited genetic population structure within Europe; however, field studies have detected high levels of philopatry, which are expected to increase population structure. Population structure will be a consequence of both contemporary dispersal and historical processes, each of which is expected to be evident at a different scale. Therefore, to gain a greater understanding of gene flow in the badger, we examined microsatellite diversity both among and within badger populations, focusing on populations from the British Isles and western Europe. We found that while populations differed in their allelic diversity, the British Isles displayed a similar degree of diversity to the rest of western Europe. The lower genetic diversity occurring in Ireland, Norway and Scotland was more likely to have resulted from founder effects rather than contemporary population density. While there was significant population structure (FST = 0.19), divergence among populations was generally well explained by geographic distance (P < 0.0001) across the entire range studied of more than 3000 km. Transient effects from the Pleistocene appear to have been replaced by a strong pattern of genetic isolation by distance across western Europe, suggestive of colonization from a single refugium. Analysis of individuals within British populations through Mantel tests and spatial autocorrelation demonstrated that there was significant local population structure across 3–30 km, confirming that dispersal is indeed restricted. The isolation by distance observed among badger populations across western Europe is likely to be a consequence of this restricted local dispersal.