bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune responses to birch in young children during their first 7 years of life
Authors: Böttcher M. F. , Jenmalm M. C. , Björkstén B. 
Published: March 2003

SummaryBackground The character of immune responses to allergens during the first years of life may decide whether the individual will become tolerant or develop allergy later in life.Objective To study the development of immune responses to the seasonal inhalant allergen birch over the first 7 years of life.Methods Blood samples were obtained from 21 children who were followed prospectively from the second to the seventh pollen season of life. Birch‐induced cytokine production and IgG subclass antibodies to rBet v 1 were analysed with ELISA, mRNA expression with real time PCR, IgE antibodies to birch with Magic LiteTM and birch‐induced mononuclear cell proliferation with 3H‐thymidine incorporation.Results Birch‐induced IFN‐γ and IL‐10 production increased with age, both in atopic and non‐atopic children, while birch‐induced IL‐13 production decreased. The two children who were sensitized and developed clinical allergy to birch showed persistent IL‐4 and IL‐5 production and IL‐9 mRNA expression, as well as Th2‐associated IgG4 responses. Transient Th2‐like responses were observed among the other children. Proliferative responses and IgG1 antibodies were seen in all children.Conclusions Immune responses to birch can be demonstrated in all children, during the first 7 years of life, regardless of atopic status. A transient early Th2‐like response is down‐regulated after the fourth pollen season, except in children who develop clinical allergy to the particular allergen.
High prevalence of current asthma and active smoking effect among the elderly
Authors: Kim Y.‐K. , Kim S.‐H. , Tak Y.‐J. , Jee Y.‐K. , Lee B.‐J. , Kim S.‐H. , Park H.‐W. , Jung J.‐W. , Bahn J.‐W. , Chang Y.‐S. , Choi D.‐C. , Chang S.‐I. , Min K.‐U. , Kim Y.‐Y. , Cho S.‐H. 
Published: March 2003

SummaryBackground Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted.Objective To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population.Methods A total of 2467 adults, who were randomly selected from metropolitan urban, non‐metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens.Results The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40‐ to 54‐year‐olds, 7.7% in 55‐ to 64‐year‐olds and 12.7% in those aged 65 or higher. For subjects of 55–64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper‐responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1).Conclusion The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper‐responsiveness among the elderly.
Concentrations of exhaled nitric oxide in asthmatics and subjects with allergic rhinitis sensitized to the same pollen allergen1
Authors: Prieto L. , Gutiérrez V. , Uixera S. , Bruno L. 
Published: March 2003

SummaryBackground Some studies have reported that the levels of exhaled nitric oxide (ENO) in asthmatics are similar to those in subjects with allergic rhinitis, and it has been postulated that atopic status might be the determinant of enhanced nitric oxide production in asthma.Objectives The aim of this study was to determine differences in ENO levels between asthmatics and subjects with allergic rhinitis sensitized to the same allergen, and to correlate these levels with airway responsiveness.Methods Nineteen patients with asthma and 18 subjects with allergic rhinitis monosensitized to Parietaria pollen were enrolled in the study. ENO values and airway responsiveness to methacholine and adenosine 5′‐monophosphate (AMP) were measured during the pollen season. The response to each bronchoconstrictor agent was measured by the provocative concentration required to produce a 20% fall in FEV1 (PC20). ENO was measured with the single‐exhalation method.Results The geometric mean (95% confidence interval) ENO values were significantly higher in asthmatics than in subjects with allergic rhinitis: 72.4 p.p.b. (54.9–93.3 p.p.b) vs. 44.7 p.p.b. (30.9–64.6 p.p.b., P = 0.03). In asthmatics, a significant correlation was found between ENO and PC20 AMP values (ρ = −0.57, P = 0.02), whereas no correlation was detected between ENO and PC20 methacholine (ρ =− 0.35, P = 0.14).Conclusions Our results suggest that atopy is not the only determinant of increased ENO levels detected in subjects with asthma, and that responsiveness to AMP may be a more sensitive marker for assessing airway inflammation in asthma compared to methacholine.
Persistence of bronchopulmonary hyper‐reactivity and eosinophilic lung inflammation after anti‐IL‐5 or ‐IL‐13 treatment in allergic BALB/c and IL‐4Rα knockout mice
Authors: Proust B. , Nahori M. A. , Ruffie C. , Lefort J. , Vargaftig B. B. 
Published: March 2003

SummaryBackground Antigen‐induced bronchopulmonary hyper‐reactivity (BHR) is generally associated with eosinophilia. It involves cytokines produced by Th2 lymphocytes, including IL‐4, IL‐5 and IL‐13, which are implicated in IgE production, eosinophil differentiation and attraction, and related events relevant to allergic inflammation, whose mechanisms remain unclear.Objective To investigate the mechanisms by which Th2 cytokines mediate eosinophilia and subsequent BHR using ovalbumin (OVA)‐immunized and OVA‐challenged IL‐4Rα–/– and IL‐4–/– mice, which fail to transduce and/or to produce IL‐4 and IgE as compared with wild type (WT) mice, and specific neutralizing antibodies.Methods On days 0 and 7, mice were immunized subcutaneously (s.c.) with OVA. At day 14, anti‐IL‐5 or anti‐IL‐13 antibodies were administered intranasally and/or intravenously before allergenic challenge. Different functional and cellular parameters were studied in vivo and cytokine production was followed with a newly described ex vivo procedure using lung explants.Results IL‐4Rα–/– and IL‐4–/– mice developed BHR and pulmonary eosinophilia, even though eosinophil recruitment to the bronchoalveolar liquid lavage (BALF) was reduced. In vivo, IL‐4–/– and IL‐4Rα–/– mice produced, respectively, no or reduced amounts of IL‐5 in the BALF/serum as compared with WT mice, whereas no IL‐13 in the BALF was detected. By contrast, ex vivo, surviving lung explants from WT and IL‐4–/– or IL‐4Rα–/– mice produced IL‐13 and large amounts of IL‐5. The neutralization of IL‐5 in vivo (BALF and serum) and ex vivo (from lung explant) in IL‐4Rα–/– and WT mice failed to suppress BHR and lung eosinophilia, and to modify IL‐13 production ex vivo. In addition, neutralization of IL‐13 in vivo from lung explant also failed to abrogate BHR and lung eosinophilia, whereas IL‐5 was unchanged.Conclusion Antigen‐induced BHR can develop independently from IL‐4, IL‐5 or IL‐13 and from the IL‐4α receptor chain, suggesting a possible novel IL‐4, IL‐5 and IL‐13‐independent pathway for the development of BHR in allergic BALB/c mice. The failure of IL‐5 or IL‐13 antibodies to prevent BHR in IL‐4Rα–/– mice suggests that neither is indispensable for BHR but does not exclude a role for lung tissue eosinophilia.
Anti‐inflammatory effects of high‐dose montelukast in an animal model of acute asthma
Authors: Wu A. Y. , Chik S. C. , Chan A. W. , Li Z. , Tsang K. W. , Li W. 
Published: March 2003

SummaryBackground Asthmatic inflammation is mediated by a network of cytokines, chemokines and adhesion molecules. Corticosteroids are the only effective agents available to control asthmatic inflammation. We investigated the effect of high‐dose montelukast (MK), a selective cysteinyl leukotriene receptor 1 antagonist, on mediators of airway inflammation.Objective The aim of this study was to determine the effect of a 3‐day course of high‐dose MK on mediators of airway inflammation induced by a single allergen challenge in sensitized mice.Methods Ovalbumin (OVA)‐sensitized BALB/c mice were treated with 25 mg/kg of MK or saline intravenously for 3 days. On the third day, a single inhalation challenge with OVA was given. Cellular infiltration was assessed in the bronchoalveolar lavage (BAL) and in the lung. Expression of IL‐4, IL‐5, IL‐13 and eotaxin in the BAL, and the lung was determined. Serum IL‐5 and total IgE was measured. IL‐5 and eotaxin mRNA expression in the lung was determined. Finally, eotaxin and VACM‐1 expression in the lung was assessed by immunohistochemistry.Results MK reduced the number of eosinophils in the BAL by > 90%. There was also significant reduction in IL‐5 in the BAL, lung and the serum, and IL‐5 mRNA expression in the lung. IL‐4 level in the lung and BAL, and IL‐13 level in the lung also significantly decreased. Serum IgE level and lung VCAM‐1 expression was also significantly lower in treated animals, but eotaxin protein and mRNA expression in the lung remained unchanged.Conclusion MK exerts its anti‐inflammatory effect through the suppression of T helper type‐2 (Th2) cytokines. The use of high‐dose MK as an anti‐inflammatory agent in acute asthma should be further explored.
Inverse modulation of IL-10 and IL-12 in the blood of women with preneoplastic lesions of the uterine cervix
Authors: Jacobs N , Giannini S L , Doyen J , Baptista A , Moutschen M , Boniver J , Delvenne P 
Published: March 2003

AbstractIt has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the cytokine production in the blood of patients with squamous intraepithelial lesions (SIL) of the uterine cervix. The levels of type-1 (interferon-gamma (IFN-γ) and IL-12) and type-2 (IL-4 and IL-10) cytokines were measured in whole blood culture supernatants of patients with low- and high-grade SIL and control women. There was no difference in IL-4 and IFN-γ levels between patients with SIL and the control group. In contrast, the ratio of IL-12/IL-10 levels was significantly lower in patients with SIL compared with the control group. A lower IL-12/IL-10 ratio in women with SIL was also observed when peripheral blood mononuclear cell (PBMC) culture supernatants and plasma samples were analysed. In patients, neither the lower expression of the CD3ε chain nor the higher frequency of HLA-DRB1*1501 expression could be correlated with abnormal cytokine production. These results suggest that a part of the cytokine network, namely IL-10 and IL-12, is perturbed in patients with SIL. A better knowledge of the role of these cytokines in regulating the growth of HPV-associated SIL might have practical implications for the development of vaccines or immunomodulatory strategies in the treatment of cervical cancers.
A restricted T cell response to myelin basic protein (MBP) is stable in multiple sclerosis (MS) patients
Authors: Uccelli A , Giunti D , Salvetti M , Ristori G , Fenoglio D , Abbruzzese M , Mancardi G L 
Published: March 2003

AbstractThe close resemblance of MS to the animal model experimental autoimmune encephalomyelitis (EAE) has provided compelling data sustaining a pathogenic role of circulating T cells reactive against MBP. T cell antigen receptor (TCR) usage in EAE is commonly considered restricted; nevertheless, dynamic changes of TCR usage correlate with the course of EAE, resulting in a limited repertoire during early stages of disease activity followed by the recruitment of other T cells reactive against new determinants. Although a broader TCR repertoire mediates the response to MBP in humans, a restricted intra-individual heterogeneity may occur in some MS patients. In the present study we characterize the response to MBP in MS subjects with relapsing remitting disease from two sampling time points 12 months apart. MBP-specific T cell lines (TCL) were first generated from eight MS individuals and two healthy subjects. New TCL were obtained after 12 months from one control and three MS patients whose response, at the first time point, was directed against a single epitope. Interestingly, these three subjects had a stable and mild disease. Few TCL obtained at two time points from the MS individuals recognized the same immunodominant epitope and shared identical TCR Vβ sequences. In the control we could not detect a restriction of the repertoire. These findings suggest that in some MS patients with benign disease a predominant T cell response to a single determinant may be detectable at different moments and is mediated by clonally expanded populations.
Apoptosis of colorectal adenocarcinoma (COLO 201) by tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ), resulting from down-modulation of Bcl-2 expression
Authors: Koshiji M , Adachi Y , Sogo S , Taketani S , Oyaizu N , Than S O E , Inaba M , Phawa S , Hioki K , Ikehara S 
Published: March 2003

AbstractFas antigen is constitutively expressed in the normal colon epithelium, but considerably diminished in most colorectal carcinomas. In the present study, we examine the relationship between Fas antigen expression and apoptosis using the colorectal carcinoma cell line COLO 201, on which a low grade of Fas antigen is expressed. Anti-Fas antibody had no effect on the induction of apoptosis of COLO 201. However, TNF-α and/or IFN-γ, independently and additively, up-regulated Fas antigen expression on COLO 201 and induced apoptosis in a dose-dependent manner. Both cytokines also increased the COLO 201 sensitivity to anti-Fas antibody, resulting from the down-modulation of Bcl-2 and the up-regulation of Bax. These findings indicate that cytokine(s) plus anti-Fas antibody (which mimics natural Fas ligand) are more effective in inducing apoptosis of COLO 201 than cytokine(s) alone. These findings suggest that immunotherapy in combination with cytokine(s) and lymphokine-activated killer (LAK) cells will become a more effective therapy for cancer than cytokine(s) or LAK cells alone, since the Fas ligand is expressed on activated T cells, natural killer cells and macrophages.
Mapping epitopes for 20 monoclonal antibodies to CR1
Authors: Nickells M , Hauhart R , Krych M , Bala Subramanian V , Geoghegan-Barek K , Marsh H C , Atkinson J P 
Published: March 2003

SUMMARYComplement receptor type one (CR1; CD35) binds and processes C3b and C4b opsonized immune complexes and regulates complement activation. We have characterized the epitopes of 13 previously reported and seven new MoAbs to human CR1. The MoAbs formed seven groups based on their reactivity with a panel of deletion forms of CR1. Seventeen of the MoAbs reacted with CR1 at more than one site, a consequence of its repetitive sequence. All five of the MoAbs recognizing epitopes in the nearly identical repeats 3, 10, and 17, as well as one MoAb which reacted with repeats 8 or 1/2 of 9 and 15 or 1/2 of 16, blocked cofactor activity for C3b. Knowledge of the repeats bearing the epitopes for these MoAbs should facilitate the further characterization of CR1.
Recombinant human IL-16 inhibits HIV-1 replication and protects against activation-induced cell death (AICD)
Authors: Idziorek T , Khalife J , Billaut-Mulot O , Hermann E , Aumercier M , Mouton Y , Capron A , Bahr G M 
Published: March 2003

SUMMARYThe chemoattractant cytokine IL-16 has been reported to suppress lymphocyte activation and to inhibit HIV-1 replication in acutely infected T cells. We have cloned and expressed human IL-16 in Escherichia coli and investigated whether the recombinant protein could regulate the level of lymphocyte apoptosis from HIV-1-infected subjects. After purification and refolding, only 2–10% of the recombinant cytokine was present in a biologically active homotetrameric form. This could explain the need for high concentrations of the bacterially derived IL-16 to induce significant inhibition of HIV-1 replication. Addition of IL-16 to unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-1-infected subjects did not modify the observed level of spontaneous lymphocyte apoptosis. In contrast, IL-16 added to PBMC cultures stimulated with anti-CD3, anti-CD95 or dexamethasone reduced significantly the percentage of lymphocytes undergoing AICD. This effect was found to correlate with the ability of the cytokine to decrease CD95 expression on activated CD4+ T cells. Comparative studies on PBMC from healthy individuals indicated that the regulation of apoptosis levels by IL-16 is a complex phenomenon and could depend on the nature of the activator used and/or the immune status of lymphocytes tested. The outcome of CD4 cross-linking on T cells by various ligands is discussed in the context of the observed beneficial activities of IL-16 and its potential role in the treatment of HIV disease.
Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase
Authors: Sack S Z , Liu Y , German J , Green N S 
Published: March 2003

SUMMARYImmunoglobulin gene somatic mutation leads to antibody affinity maturation through the introduction of multiple point mutations in the antigen binding site. No genes have as yet been identified that participate in this process. Bloom's syndrome (BS) is a chromosomal breakage disorder with a mutator phenotype. Most affected individuals exhibit an immunodeficiency of undetermined aetiology. The gene for this disorder, BLM, has recently been identified as a DNA helicase. If this gene were to play a role in immunoglobulin mutation, then people with BS may lack normally mutated antibodies. Since germ-line, non-mutated immunoglobulin genes generally produce low affinity antibodies, impaired helicase activity might be manifested as the immunodeficiency found in BS. Therefore, we asked whether BLM is specifically involved in immunoglobulin hypermutation. Sequences of immunoglobulin variable (V) regions were analysed from small unsorted blood samples obtained from BS individuals and compared with germ-line sequences. BS V regions displayed the normal distribution of mutations, indicating that the defect in BS is not related to the mechanism of somatic mutation. These data strongly argue against BLM being involved in this process. The genetic approach to identifying the genes involved in immunoglobulin mutation will require further studies of DNA repair- and immunodeficient individuals.
Sulphatide-binding properties are shared by serum amyloid P component and a polyreactive germ-line IgM autoantibody, the TH3 idiotype
Authors: Wheeler P R , Raynes J G , O'Sullivan G M , Duggan D , McAdam K P W J 
Published: March 2003

SUMMARY
Serum amyloid P component (SAP) concentration was elevated in sera from leprosy patients, significantly so above endemic controls in lepromatous cases. In the sera of lepromatous leprosy (LL) patients who experienced an erythema nodosum leprosum (ENL) episode the SAP fell at the onset of ENL and remained low throughout, in two of three cases. Changes in SAP concentration parallel anti-sulphatide IgM concentrations. TH3, a monoclonal IgM germ-line antibody derived from a LL patient, and SAP share similar binding patterns. In this study we demonstrate binding to heparin and sulphatide. Moreover, SAP inhibited the binding of TH3 to sulphatide, as well as anti-sulphatide IgM found in a range of sera, and anti-sulphatide IgG in the only sera sample in which it was found. The observation that anti-TH3 idiotype monoclonal and polyclonal anti-SAP antibodies both inhibited the binding of TH3 and IgM in sera (but not IgG) to sulphatide without binding to sulphatide themselves further demonstrated similar binding specificities. The observations of similarity in binding reinforce ideas that SAP may function as a primitive opsonin, but the clear ability to inhibit binding of autoantibodies suggests that SAP may play a role in ameliorating tissue and particularly nerve damage in leprosy patients.
Quantitative intracellular cytokine measurement: age-related changes in proinflammatory cytokine production
Authors: O'Mahony L , Holland J , Jackson J , Feighery C , Hennessy T P J , Mealy K 
Published: March 2003

SUMMARYThe proinflammatory cytokines play a central role in mediating cellular and physiological responses, and levels may reflect immune system effectiveness. In this study, the effect of ageing on the inflammatory response was examined using a novel method to detect production of the proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-α), IL-6 and IL-1β. Peripheral blood mononuclear cells (PBMC) obtained from healthy donors of different ages were incubated for 0, 24, 48 and 72 h with or without phorbol 12-myristate 13-acetate (PMA) stimulation. At each time point these cells were permeabilized and incubated with secondary conjugated FITC MoAbs specific for each cytokine. A flow cytometric system was developed to quantify specific intracellular fluorescence in T cells (CD3+) and monocytes (CD14+). TNF-α, IL-6 and IL-1β production in cell culture supernatants was also measured using ELISAs. In older subjects, flow cytometry detected significant increases in intracellular T cell TNF-α and IL-6 (P &lt; 0.05). IL-1β was not detected in any of the T cell samples. Likewise, the monocytes of older subjects demonstrated increased intracellular levels of all three cytokines, but these increases were not significant (P &gt; 0.05). These changes in intracellular proinflammatory cytokine levels may explain some of the exaggerated inflammatory responses seen in elderly patients.
Immunological study on CD3 defective cutaneous T cell lymphoma cells from a patient with Sézary syndrome
Authors: Sano S , Matsui Y , Itami S , Yoshikawa K 
Published: March 2003

SUMMARYHere we investigated the nature of cutaneous T cell lymphoma (CTCL) cells lacking surface CD3. A large number of CD3−CD4 T cells were found in the peripheral blood and lesional skin of a patient with Sézary syndrome, which is a variant of CTCL. Southern blot analysis revealed that a clonal rearrangement of T cell receptor (TCR) genes was detected in the separated CD3−CD4 cells, whereas CD3+CD4 cells showed no clonal rearrangement, indicating that the CD3−CD4 cells represented CTCL cells. However, the CTCL cells expressed TCR with a particular Vβ apart from CD3. The CTCL cells showed significant responses to staphylococcal enterotoxins (SEs) in vitro, although they hardly responded to phytohaemagglutinin, Mycobacterium tuberculosis antigen, and alloantigen. They required antigen-presenting cells (APC) to respond to SEB. Blocking analyses with MoAbs revealed that they recognized SEB through TCR depending on HLA-DR and intercellular adhesion molecule-1 (ICAM-1). Taken collectively, these results indicate that the CTCL cells lacking surface CD3 could proliferate in response to bacterial superantigens, whereas the responses to conventional antigens were generally suppressed. These results also implied that CTCL could be exacerbated by bacterial infection.