bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harm reduction interventions, behaviours and associated health outcomes in France, 1996–2003
Authors: Emmanuelli Julien , Desenclos Jean‐Claude 
Published: October 2005

ABSTRACTAims  To track the effect of the French harm reduction programme targeted at intravenous drug users (IDUs) and associated health outcomes.Material  Since 1996, we have collected monthly sales of sterile syringes and substitution treatments (buprenorphine high dosage and methadone) sold to IDUs in the 23 000 pharmacies in France and collated these figures in a single data base (SIAMOIS). To this data base we have also added the number of syringes distributed through community associations, as well as methadone treatments prescribed in public drug dependence clinics.Methods  For the period 1996–2003 we analysed syringe sales and prescribed substitution treatments as indicators of access to harm reduction services. We compared variations of these figures over time with trends in health outcome indicators [annual number of fatal overdoses, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) prevalence among intravenous drug users], risk behaviour indicators (rate of syringe sharing or rate of syringe re‐use) and legal indicators (heroin and cocaine use‐related arrests).Findings  The number of sterile syringes sold or distributed to IDUs increased from 1996 to 1999 (+ 21%) and then decreased dramatically from 1999 to 2003 (−40%). In 2003, we estimated that more than 100 000 drug users used substitution treatments. Between 1996 and 2003, a decrease in syringe sharing and syringe re‐use was observed, HIV prevalence among IDUs decreased from 40% to 20% and HCV prevalence remained high (60–70%). From 1996 to 2003, arrests due to heroin use declined (from 17 328 to 4025) and deaths due to overdoses also decreased (from 465 to 89), whereas arrests for cocaine use increased from 1184 to 2511.Conclusion  Our results indicate that, since 1996 in France, IDUs have had greatly improved access to sterile syringes and substitution treatments. The decrease in syringe sharing and re‐use practices and of HIV prevalence during the same time period indicates that the harm reduction policy implemented in France has had a positive impact. However, because of the persistent sharing and re‐use of syringes and a remaining high HCV prevalence in IDUs, efforts to facilitate access to sterile syringes must continue, and targeting of at‐risk groups must be improved. Behavioural surveys associated with HIV and HCV seroprevalence data are needed to further assess prevention of blood‐borne infections among IDUs in France.
Anisakis simplexallergy: a murine model of anaphylaxis induced by parasitic proteins displays a mixed Th1/Th2 pattern
Authors: Baeza M L , Conejero L , Higaki Y , Martín E , Pérez C , Infante S , Rubio M , Zubeldia J M 
Published: October 2005

SummaryThe study of the singular hypersensitivity reactions to Anisakis simplex (A.s) proteins, may help us to undestand many of the unknown immune interactions between helmiths infections and allergy. We have developed a murine model of allergy to A. simplex, that mimics human A. simplex allergy to study the specific aspects of anaphylaxis induced by parasites. Male C3H/HeJ mice were intraperitoneally sensitized to A. simplex. Mice were then intravenous or orally challenged with A. simplex. Antigen-specific immunoglobulins, polyclonal IgE, anaphylactic symptoms, plasma histamine levels and cytokine profiles were determined. Comparative IgE immunoblot analyses were also performed. Specific IgE, IgG1 and IgG2a were detected in sensitized mice since week 3. Polyclonal IgE raised and peaked with different kinetics. Intravenous A. simplex challenge produced anaphylaxis in mice, accompanied by plasma histamine release. Oral A. simplex challenge in similarly sensitized mice did not caused symptoms nor histamine release. Numerous A. simplex allergens were recognized by sensitized mouse sera, some of them similar to human serum. The A. simplex stimulated splenocytes released IL-10, IFN-γ, IL-4, IL-13 and IL-5. We describe a new animal model of anaphylaxis. It exhibits characteristics of type I hypersensitivity reactions to Anisakis simplex similar to those observed in allergic humans. Different responses to i.v. or oral A. simplex challenges emerged, which did not reflect a window tolerization period. The cytokine profile developed (mixed Th1/Th2 pattern) differed from the observed in classical models of anaphylaxis or allergy to food antigens. This model may permit to investigate the peculiar allergic reactions to parasitic proteins.
Immunoglobulin treatment reduces atherosclerosis in apolipoprotein E–/– low-density lipoprotein receptor –/– mice via the complement system
Authors: Persson L , Borén J , Nicoletti A , Hansson G K , Pekna M 
Published: October 2005

SummaryAtherosclerosis is associated with activation of the immune system. Intravenously applied normal polyclonal immunoglobulins (IVIg) have broad therapeutic applications in the treatment of autoimmune and systemic inflammatory diseases. Recently, IVIg have been shown to inhibit atherogenesis in experimental animal models. To investigate the role of the complement system in this process, we used third complement component-deficient  (C3–/–) and control atherosclerosis-prone apolipoprotein E (ApoE) and low-density  lipoprotein  receptor  (LDLR)  double  knock-out  mice  fed  a normal diet. IVIg treatment reduced lesion fraction area in the aortic root of complement-sufficient mice whereas the lesion fraction area of C3–/– mice was not affected. Thus, complement activation plays a role in the anti-atherosclerotic effects of IVIg, possibly by C3-derived fragments generated through Fc-dependent complement activation.
Activation of c-Jun N-terminal kinase (JNK) signalling in experimentally induced gastric lesions in rats
Authors: Mitsuyama K , Tsuruta O , Matsui Y , Harada K , Tomiyasu N , Suzuki A , Takaki K , Masuda J , Handa K , Satoh Y , Bennett B L , Toyonaga A , Sata M 
Published: October 2005

SummaryThe c-Jun N-terminal kinase (JNK) participates in intracellular signalling cascades that mediate inflammatory responses. Therefore, the JNK signalling may be involved in gastric injury and inhibition of this pathway may form the basis of a new strategy for the treatment of gastric injury. The aim of this study was to determine whether JNK participates in the formation of gastric lesions in an experimental model. Acute gastric injury was induced in Sprague-Dawley rats by intragastric administration of 100% ethanol. The amount of phospho-JNK in the rat stomach was determined using immunohistochemistry and Western analysis. Animals received subcutaneous injections of a specific JNK inhibitor SP600125 or vehicle and the extent of mucosal damage in the stomach was determined. Western analysis revealed early phosphorylation of JNK and, to a lesser extent, p38 as well as late phosphorylation of the p42/44 extracellular signal-related kinases during the development of gastric lesions. JNK was phosphorylated in epithelial cells and in occasional mononuclear cells present at lesion sites. These cells were rarely found in samples from control specimens. Treatment with SP600125 significantly reduced the extent of gastric lesions. These findings indicate that experimental gastric injury is associated with activation of the JNK signalling pathway, and also suggest that JNK inhibitors may play a role in the treatment of gastric injury in humans.
O-glycosylatedversusnon-glycosylated MUC1-derived peptides as potential targets for cytotoxic immunotherapy of carcinoma
Authors: Stepensky D , Tzehoval E , Vadai E , Eisenbach L 
Published: October 2005

SummaryDue to the fact that many cellular proteins are extensively glycosylated, processing and presentation mechanisms are expected to produce a pool of major histocompatibility complex (MHC) class I-bound protein-derived peptides, part of which retain sugar moieties. The immunogenic properties of the presented glycosylated peptides in comparison to their non-glycosylated counterparts have not been determined clearly. We assessed the cellular immunogenicity of MUC1 (mucin)-derived peptides O-glycosylated with a Tn epitope (GalNAc) using HLA-A*0201 single chain (HHD)-transfected cell lines and transgenic mice. For part of the compounds Tn moiety did not interfere with the HLA-A*0201 binding. Moreover, part of the glycopeptides elicited effective cytotoxic responses, indicating recognition of the glycopeptide-HLA-A*0201 complex by the T cell receptor (TCR) and subsequent cytotoxic T lymphocyte (CTL) activation. The CTLs exhibited a substantial degree of cross-reactivity against target cells loaded with glycosylated and non-glycosylated forms of the same peptide. The studied (glyco)peptides showed cellular immunogenicity in both MUC1-HHD and HHD mice and induced effective lysis of (glyco)peptide-loaded target cells in CTL assays. However, the elicited CTLs did not induce selective lysis of human MUC1-expressing murine cell lines. Moreover, immunization with (glyco)peptide-loaded dendritic cells (DCs) did not induce significant immunotherapeutic effects. We conclude that Tn glycosylated MUC1-derived peptides can be presented by MHC class I molecules, and may be recognized by specific TCR molecules resulting in cytotoxic immune responses. However, the studied glycopeptides did not offer significant benefit as targets for cytotoxic immune response due apparently to (a) cross-reactivity of the elicited CTLs against the glycosylated and non-glycosylated forms of the same peptide and (b) low abundance of glycopeptides on tumour target cells.
Tolerosome‐induced oral tolerance is MHC dependent
Authors: Östman Sofia , Taube Maria , Telemo Esbjörn 
Published: October 2005

SummaryOral administration of a protein antigen generates a serum factor that induces tolerance when transferred into naïve recipients. This serum factor has been described in rats as consisting of exosome‐like structures or tolerosomes, which express major histocompatibility complex class II molecules (MHCII) and mediate antigen‐specific tolerance. In this study, we investigated the functions of serum‐derived tolerosomes both in vivo and in vitro. Tolerosomes were purified from the 100 000 g pellet fraction of serum from ovalbumin (OVA)‐fed mice. When transferred into naïve recipient mice, the tolerosomes mediated OVA‐specific tolerance. We also found that tolerosomes from OVA‐fed mice induced the activation of OVA‐specific T cells both in vivo and in vitro. The inoculation of severe combined immunodeficiency (SCID) mice with an interferon‐γ‐producing cell line normalized the expression of MHCII in the intestinal epithelial cells and restored their ability to generate tolerosomes. Syngeneic but not allogeneic transfer of tolerosomes from OVA‐fed donors induced tolerance in the recipients. Our results show that tolerosomes can be isolated from mouse serum, that tolerosome‐induced oral tolerance requires MHCII expression in intestinal epithelial cells, and that tolerosomes are functional only in syngeneic recipients.
Induction and recall of immune memory by mucosal immunization with a non‐toxic recombinant enterotoxin‐based chimeric protein
Authors: Gockel Christine M. , Russell Michael W. 
Published: October 2005

SummaryPrevious reports have suggested that peroral delivery of antigens chemically coupled to non‐toxic recombinant enterotoxin B subunits, such as the cholera toxin B subunit (CTB), induces tolerance to the antigen that may be abrogated by the toxic enzyme activity of intact enterotoxins, such as cholera toxin (CT). The aim of this study was to examine the immunogenicity of a genetically coupled protein composed of the saliva‐binding region (SBR) of the Streptococcus mutans surface antigen AgI/II and the non‐toxic A2 and B subunits of CT (SBR‐CTA2/B) compared with that of recombinant SBR admixed with CT (SBR + CT) and SBR chemically coupled to recombinant CTB (SBR‐CTB) following peroral delivery by intragastric (i.g.) immunization. The results showed that i.g. immunization with SBR‐CTA2/B, like SBR + CT, induced antigen‐specific serum immunoglobulin G (IgG) and salivary IgA antibodies, and sensitized splenic T cells. Comparison studies with SBR‐CTB produced serum IgG but not salivary IgA titres and failed to sensitize splenic cells. Immunization with SBR‐CTA2/B via the intranasal route also primed for the recall of antigen‐specific memory antibody responses 6 months later. These findings show that SBR‐CTA2/B is an immunogenic, not tolerogenic, chimeric protein that can induce and recall antigen‐specific memory responses upon mucosal immunization.
Cathepsin S is not crucial to TSHR processing and presentation in a murine model of Graves' disease
Authors: Kala Mrinalini , Chen Chun‐Rong , McLachlan Sandra M. , Rapoport Basil , Aliesky Holly , Chapman Harold A. 
Published: October 2005

SummaryBy regulating invariant (Ii) chain processing and MHC class II peptide loading, the endosomal protease cathepsin S (Cat S) has a potential role in autoimmune susceptibility. Indeed, Cat S null mice are resistant to I‐Ab‐restricted experimental myasthenia gravis due to inadequate peptide presentation. To explore the role of Cat S in a Graves' disease model, I‐Ad‐restricted wild‐type (WT) and Cat S–/– mice were immunized with adenovirus encoding the A subunit of thyroid stimulating hormone receptor (TSHR). TSHR adenovirus immunized mice develop Th1 T cells, TSHR antibodies, and a proportion become overtly hyperthyroid. Although TSHR presentation in vitro was initially impaired in Cat S–/– mice, subsequent TSHR presentation in vitro and disease development were similar in both groups but with higher antibody responses in Cat S null mice. WT and Cat S–/– mice recognized similar T cell epitopes from a panel of overlapping TSHR peptides. TSHR responses were found to be I‐Ad‐restricted and Cat S–/– I‐Ad B cells had marked defects in Ii processing. These data imply that loading of TSHR peptides critical to TSHR antibody responses becomes Ii‐independent. Contrasting findings among organ‐specific murine autoimmune models imply that potential uses of Cat S inhibitors to ameliorate autoimmunity must be determined empirically.
Putting the natural killer cell in its place
Authors: O'Connor Geraldine M. , Hart Orla M. , Gardiner Clair M. 
Published: October 2005

SummaryNatural killer (NK) cells were originally described as ‘null’ lymphocytes, but we have increasing evidence of their role in recognizing pathogen, and our knowledge of NK cell receptors continues to expand exponentially. Human NK cells have many receptors for human leucoctye antigen (HLA) class I. These killer immunoglobulin‐like receptors (KIRs) and CD94/NKG2 receptors can signal in both positive and negative ways to regulate NK cell functions. The inhibitory receptors are the best characterized, but even in these cases much of their functional biology remains elusive. In this review, some recent advances in terms of the three‐immunoglobulin (3Ig)‐domain KIRs are discussed. Natural cytotoxicity receptors (NCRs) are among the activatory receptors found on NK cells. While pathogen ligands for these receptors have been described, endogenous ligands remain elusive. NCRs and NKG2D, a receptor for stress‐induced antigens, appear to play complementary functional roles in terms of NK cell activation. More recently described on NK cells are the Toll‐like receptors. In particular, these receptors of the innate immune system allow NK cells to directly sense pathogen, and their ligation on accessory cells indirectly activates NK cells through cytokine production. It is becoming clear that none of these receptor systems functions in isolation and that it is the sum of the signals (which will reflect the pathogenic situation), in addition to the cytokine milieu, that will direct NK cell activation. The resulting cytotoxicity, cytokine production and direct cell–cell regulatory interactions with other cells of the immune system, for example dendritic cells, ultimately determine the role of the NK cell in the context of an overall immune response.
Characterization of a novel PMA‐inducible pathway of interleukin‐13 gene expression in T cells
Authors: Keen Judith C. , Cianferoni Antonella , Florio Giovanni , Guo Jia , Chen Rongbing , Roman Jessica , Wills‐Karp Marsha , Casolaro Vincenzo , Georas Steve N. 
Published: October 2005

SummaryAlthough interleukin 13 (IL‐13) is an important mediator of asthma and allergic diseases, the molecular mechanisms regulating IL‐13 gene expression are not well understood. This study was designed to define the molecular mechanisms governing IL‐13 gene expression in T cells. IL‐13 expression was examined in human peripheral blood T cells and in the EL‐4 T‐cell line by enzyme‐linked immunosorbent assay and reverse‐transcription polymerase chain reaction. An IL‐13 promoter deletion analysis was performed using luciferase‐based reporter plasmids transiently transfected into EL‐4 cells by electroporation. DNA binding factors were investigated using electrophoretic mobility shift assays. In contrast to IL‐4 expression, which required concomitant activation of calcium‐ and protein kinase C‐ (PKC‐) dependent signalling pathways, PKC activation alone was sufficient for IL‐13 protein secretion in mitogen‐primed (but not resting) peripheral blood T cells, and for IL‐13 mRNA expression and promoter activity in EL‐4 T cells. Promoter deletion analysis localized a phorbol 12‐myristate 13‐acetate (PMA) ‐sensitive element to a proximal promoter region between − 109 and − 79 base pairs upstream from the IL‐13 transcription start site. This promoter region supported the binding of both constitutive and PMA‐inducible nuclear factors in gel shift assays.
CD2 activation of human lamina propria lymphocytes reduces CD3 responsiveness
Authors: Ebert Ellen C. 
Published: October 2005

SummaryLamina propria lymphocytes (LPLs) are thought to be antigen‐activated memory T cells. Yet, they respond better to ligation of the CD2 receptor than the CD3 receptor by mitogenic antibodies. This study defines their constitutive state of activation and relates it to their CD3 hyporesponsiveness. The activated state of LPLs was demonstrated by their heightened display of the activated CD2 epitope, T113. Constitutive CD2 activation was shown by the reduction in spontaneous proliferation when the CD2–CD58 interaction was blocked. LPLs preferentially recognized CD58 rather than the major histocompatibility complex molecules on monocytes, triggering proliferation and interferon‐γ (IFN‐γ) secretion that was inhibited by blocking the CD2–CD58 interaction. To determine whether CD2 activation of LPLs contributes to their CD3 hyporesponsiveness, they were first stimulated with mitogenic CD2 antibodies and then tested for CD3‐induced proliferation. The responses were greatly reduced by prior CD2 stimulation compared with LPLs cultured in medium alone. This effect was not caused by apoptosis or by changes in CD3 expression induced by CD2 triggering. This study shows that LPLs are constitutively activated through CD2, that they preferentially recognize CD58 on monocytes and that CD2 stimulation leads to CD3 hyporesponsiveness.
The importance of species identity in the biocontrol process: identifying the subspecies of Acacia nilotica (Leguminosae: Mimosoideae) by genetic distance and the implications for biological control
Authors: Wardill Trevor J. , Graham Glenn C. , Zalucki Myron , Palmer William A. , Playford Julia , Scott Kirsten D. 
Published: October 2005

AbstractAims  A molecular genetic distance study has been used in an initial survey to identify subspecies and genotypes of the weed Acacia nilotica in Australia, information needed to find suitable biocontrol agents. We use patterns of DNA sequence variation (in two DNA fragments) from each of the nine described subspecies of Acacia nilotica (L.) Delile (Leguminosae: Mimosoideae) that is to determine their genetic similarity, to verify if the Australian populations are A. nilotica ssp. indica (Benth.) Brenan, and to establish if any other subspecies are present in Australia.Location  Australia and southern Africa through the Arabian peninsular to the Indo‐Pakistan subcontinent.Methods  Representative specimens from the global distribution of the nine A. nilotica subspecies were sourced primarily from herbaria sheet specimens where available, and secondarily from field collections. These specimens together with related outgroups from Mimosoideae were genetically analysed using the DNA fragments trnL and internal transcribed spacer one (ITS1). We calculated a similarity index as set out in paup* using upgma (Unweighted Pair‐Group Method Arithmetic average) methods to cluster taxa to produce a genetic distance phenogram.Results  Sequence results from ITS1 and trnL DNA fragments identified seven of the described subspecies of A. nilotica. Acacia nilotica ssp. cupressiformis (J. Stewart) Ali & Faruqi and A. nilotica ssp. adstringens (Schumach. & Thonn.) Roberty were not found to be genotypically distinct from A. nilotica ssp. indica and A. nilotica ssp. nilotica, respectively, based on the two DNA fragments. Subspecific ITS1 genotypes were geographically distributed similarly to previous reports that were based on morphology, with the exception that the hemispherica ITS1 genotype also occurred in Somalia. We confirmed that the Australian A. nilotica populations are mostly comprised of subspecies indica, but in addition, some individuals were found to be genetically identical to an unidentified Pakistan genotype not previously reported as occurring in Australia.Main conclusions  Australian A. nilotica populations originated from India and Pakistan and we recommend further analysis to determine the complete genetic diversity profile and origins of the Australian populations. We highlight the importance of determining any hybridization between Australian populations of A. nilotica and native subgenus Acacia species. This study demonstrates the importance of genotyping weed species targeted for biocontrol and/or listed host specificity test species that may be easily misidentified. Biocontrol practitioners can justify genetic studies by considering the costs should a project fail through misidentification.