bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of rofecoxib in subjects with a history of adverse cutaneous reactions to aspirin and/or non‐steroidal anti‐inflammatory drugs
Authors: Pacor M. L. , Di Lorenzo G. , Biasi D. , Barbagallo M. , Corrocher R. 
Published: March 2003

Background Adverse reactions to non‐steroidal anti‐inflammatory drugs (NSAID)s are frequent, and the need to identify a safe alternative drug is a common problem in clinical practice.Objective To assess the tolerability of rofecoxib, a drug that specifically inhibits COX‐2, in a group of NSAID‐sensitive patients.Methods One‐hundred and four subjects (29 males and 75 females, mean age 35.6 ± 14.1) were enrolled. All subjects had experienced one or more episode characterized by cutaneous symptoms (erythema, and/or urticaria angioedema) following the assumption of NSAIDs; 92 subjects experienced reactions to only one NSAID (single intolerance: SI) and 12 subjects had reactions to multiple NSAIDs (multiple intolerance: MI). Rofecoxib was challenged at the following dosages: ¼ of 25 mg (6.25 mg), ¼ of 25 mg, and ½ of 25 mg (12.5 mg), at intervals of 1 h if no symptoms had developed with the previous administration, in order to reach a cumulative dose of 25 mg. All subjects underwent two double‐blind, placebo‐controlled challenges in two consecutive days.Results No reactions against placebo were observed. Similarly, no reactions were observed in all subjects both after the first and after the second challenge to rofecoxib.Conclusions The present study demonstrated that rofecoxib does not have cross‐reactivity to NSAIDs. Rofecoxib is a safe alternative in subjects with previous adverse cutaneous reaction to NSAIDs.
Intranasal application of purified protein derivative suppresses the initiation but not the exacerbation of allergic rhinitis in mice
Authors: Hattori H. , Okano M. , Yamamoto T. , Yoshino T. , Yamashita Y. , Watanabe T. , Satoskar A. R. , Harn D. A. , Nishizaki K. 
Published: March 2003

SummaryBackground Several epidemiological and experimental studies have demonstrated that exposure to pathogens such as those from the genus Mycobacterium leads to the suppression of allergic sensitization and inflammation. However, little is known as to whether pathogen‐derived soluble antigens have the potential to modulate the pathogenesis of allergic rhinitis.Objective We sought to determine whether application of purified protein derivative (PPD) from Mycobacterium tuberculosis can suppress the initiation and/or exacerbation of allergic rhinitis using a recently developed murine model.Methods First, we investigated whether a single intranasal application of PPD could elicit cytokine production in the nose by RT‐PCR. BALB/c mice were repeatedly sensitized with Schistosoma mansoni egg antigen (SEA) intranasally without an adjuvant. PPD was applied through different routes either before or after sensitization. The production of SEA‐specific antibodies, nasal eosinophilia and cytokines by nasal lymphocytes was compared among mice that had or had not received PPD treatment.Results IFN‐γ, but not IL‐4, was detected in the nasal tissue 12 to 48 h after a single intranasal application of 10 µg PPD. Repeated intranasal application of PPD prior to and during sensitization with SEA significantly inhibited the production of both SEA‐specific IgE/IgG1 and nasal eosinophilia. Moreover, it partially inhibited the production of IL‐4 by nasal lymphocytes in response to SEA. Conversely, this treatment led to a significant increase in IFN‐γ production. On the other hand, PPD applied through the footpad had no effect over the same period. Repeated intranasal application of PPD after sensitization with SEA had no exacerbative effect on allergic inflammation.Conclusion These results indicate that the local application of PPD, and the subsequent induction of IFN‐γ, inhibits the initiation, but not the exacerbation, of allergic rhinitis in mice. This suggests that pathogen‐derived antigens have potential for use in the prevention and prophylaxis of allergic rhinitis.
Polymorphism of the eosinophil cationic protein‐gene is related to the expression of allergic symptoms
Authors: Jönsson U. ‐B. , Byström J. , Stålenheim G. , Venge P. 
Published: March 2003

SummaryBackground We have found a polymorphism in the ECP (eosinophil cationic protein)‐gene at position 434 according to GenBank accession number NM 002935. This polymorphism would cause the change of the amino acid arginine (base at position 434 is G) at position 97 to threonine (base at position 434 is C).Objective To investigate the prevalence of the ECP‐polymorphism and to screen for disease associations.Methods DNA of 209 medical students and 76 asthmatic subjects was analysed. The 434 genotype in the ECP‐gene was detected by cleavage of the amplified DNA sequence with the restriction enzyme PstI and analysis of the cleaved product by agarose gel electrophoresis.Results The prevalences of the polymorphism in the student population were 53%, 39% and 8% for the 434GG, the 434GC and the 434CC genotype, respectively, with allele frequencies of 72% (434G) and 28% (434C). Subjects reporting allergy had a higher prevalence of the 434G allele than non‐allergic subjects (P = 0.0056). Of the students who were Phadiatop‐positive and had allergic symptoms, 79% had the 434GG genotype, whereas the 434GC and 434CC genotypes were present in 82% of those who did not express allergic symptoms (P < 0.001). Among the 76 patients with asthma, patients with allergic asthma had a significantly higher proportion of 434GG compared with patients with non‐allergic asthma (P = 0.04). None of the 18 subjects of the two groups with the 434CC genotype had allergy.Conclusion The 434(G > C) polymorphism in the ECP‐gene is related to the development of allergic symptoms, suggesting a central role for the ECP molecule in the process.
Identification of the soybean hull allergens involved in sensitization to soybean dust in a rural population from Argentina and N‐terminal sequence of a major 50 KD allergen
Authors: Codina R. , Ardusso L. , Lockey R. F. , Crisci C. D. , Jaén C. , Bertoya N. H. 
Published: March 2003

SummaryBackground Sensitization to soybean hull (SH) allergens occurs in subjects from Argentina, a soybean producer country. However, the causative allergens have not been identified. The purposes of this study are to: (i) identify the SH allergens using sera of 29 subjects with asthma and/or allergic rhinitis from Argentina exposed to soybean dust who have a positive (weal with SH/weal with histamine ≥ 0.5) skin prick test to SH; and (ii) determine the N‐terminal amino acid sequence of a major 50 K SH allergen that sensitizes this population.Methods All sera were assayed for specific IgE (RIA), IgG4 (ELISA), and IgE and IgG4‐Western blots. A sera pool from 10 healthy subjects was a negative control. N‐terminal amino acid sequencing was performed by the Edman degradation method.Results Positive specific IgE only was found in 12/29 (41.4%), IgG4 in 3/29 (10.3%), and both IgE and IgG4 in 14/29 (48.3%) sera. IgE‐Western blot demonstrates: (i) an allergen, MW 50 K (51.7% binding); (ii) one or two distinct allergens, MW < 20.2 K (72.4% binding), depending on the sera; and (iii) 1–5 additional IgE binding proteins, MW > 20.2 to < 46.9 K (41.4% binding), depending on the sera. IgG4‐Western blot demonstrates: (i) a band, MW 70K (31% binding); (ii) a band, MW 50 K (17.2% binding); (iii) one or two additional bands, MW < 20.2 K (51.7% binding), depending on the sera; and (iv) a band, MW > 20.2 to < 28.5 K (20.7% binding). The 50 K allergen N‐terminal amino acid sequence of the first 17 amino acids indicates a significant homology with chlorophyll A‐B binding protein precursors from tomato, spinach, and petunia.Conclusions Specific IgE and IgG4 to SH are common in sera from allergic individuals living in rural areas in Argentina. SH contain an IgE binding protein, MW about 50 K, not previously described. Sensitization to this allergen is common in subjects who are repeatedly exposed to soybean dust inhalation.
Reproductive history and allergic rhinitis among 31145 Danish women
Authors: Westergaard T. , Begtrup K. , Rostgaard K. , Krause T. G. , Benn C. S. , Melbye M. 
Published: March 2003

SummaryBackground and objective A successful pregnancy is associated with a strong skewing of the immune system towards a Th2‐type immune response. Because such a deviation is also the hallmark of allergic disease, it was investigated whether allergic rhinitis in women was associated with an increased likelihood of becoming pregnant and having a successful outcome of pregnancies.Material and methods Information on allergic rhinitis and reproductive history was obtained for 31145 pregnant women who participated in a national birth cohort study in Denmark during September 1997 to March 2000, and for whom complete information on siblings and place of residence and birth was available via the Civil Registration System. Data were analysed using logistic regression.Results Women who had previously been pregnant (OR = 0.91, 95% CI 0.85–0.98) or who had given birth previously (OR = 0.91, 95% CI 0.85–0.98) were less likely to report allergic rhinitis than others. The number of previous spontaneous abortions, gestational week of the first spontaneous abortion and fertility treatment were not associated with allergic rhinitis. Women who had waited less than a year to become pregnant more often had allergic rhinitis (OR = 1.18, 95% CI 1.06–1.32, P = 0.002) than women who had waited for more than a year. Early age at menarche was associated with an increased likelihood of allergic rhinitis (Ptrend = 0.003).Conclusions Our findings did not support the hypothesis that an atopic genotype overall should be associated with an increased likelihood of successful outcome of pregnancies, but it might be associated with a decreased waiting time to pregnancy.
Long‐lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10‐year prospective study
Authors: Di Rienzo V. , Marcucci F. , Puccinelli P. , Parmiani S. , Frati F. , Sensi L. , Canonica G. W. , Passalacqua G. 
Published: March 2003

SummaryBackground Subcutaneous immunotherapy for respiratory allergy has shown a long‐lasting efficacy after its discontinuation, whereas this evidence is still lacking for sublingual immunotherapy, despite the fact that it is widely used.Objective We aimed to evaluate whether a long‐lasting effect of SLIT occurs, in a prospective parallel group controlled study.Methods Sixty children (mean age 8.5 years) suffering from allergic asthma/rhinitis due to mites were subdivided into two matched groups: 35 underwent a 4‐ to 5‐year course of SLIT with standardized extract and 25 received only drug therapy. The patients were evaluated at three time points (baseline, end of SLIT and 4 to 5 years after SLIT discontinuation) regarding presence of asthma, use of anti‐asthma drugs, skin prick tests and specific IgE.Results We found that in the SLIT group there was a significant difference vs. baseline for the presence of asthma (P ≤ 0.001) and the use of asthma medications (P ≤ 0.01), whereas no difference was observed in the control group. The mean peak expiratory flow result was significantly higher in the active group than in the control group after 10 years. No change was seen as far as new sensitizations were concerned. Specific IgE showed a near‐significant increase (baseline vs. 10 years, P = 0.06) only in the control group.Conclusion Our study demonstrates that sublingual immunotherapy is effective in children and that it maintains the clinical efficacy for 4 to 5 years after discontinuation.
Epstein–Barr virus-associated peripheral T-cell lymphoma in adults with hydroa vacciniforme-like lesions
Authors: Cho Kwang-Hyun , Kim Chul-Woo , Heo Dae-Seog , Lee Dong-Soon , Choi Won-Woo , Rim Jong-Hyun , Han Won-Suk 
Published: March 2003

Abstract
We describe two Korean adult patients who had necrotizing papulovesicles mainly on their faces. Skin biopsy specimens showed perivascular and periadnexal infiltrate of atypical lymphoid cells with vasculitis in the dermis and subcutaneous tissue. In situ hybridization demonstrated a latent infection of Epstein–Barr virus in the majoriy of lymphoid cells in the dermis. These patients were diagnosed as having T-cell lymphoma. Interestingly, large granular lymphocytosis was found in the peripheral blood of Case 2.
Immunohistology of the early course of lentivirus-induced arthritis
Authors: Von Bodungen U , Lechner F , Pfister H , Vogt H R , Cheevers W P , Bertoni G , Jungi T W , Peterhans E 
Published: March 2003

SUMMARY
Caprine arthritis encephalitis (CAE) is a lentiviral infection of goats characterized by mononuclear cell infiltration of various tissues, most prominently the joints, mammary glands and, in young animals, the brain. We have investigated the early stages of arthritis induced by intracarpal and intravenous infection with molecularly cloned CAE virus. Analysis of the synovial membranes by immunohistological methods showed that the proportion of CD8+T cells peaked around day 12 post-infection. CD4+ T cells increased to a lesser degree. The relative proportion of B cells rose steadily post-infection. At 33 days post-infection, plasma cells accounted for over one third of all inflammatory cells in the inflamed synovium. Histopathologically, the arthritic lesions in the synovial membranes closely resembled those in membranes of animals with a 2-year history of chronic arthritis. Our observations indicate that this type of short-term experimental infection is particularly suitable for studying the pathogenesis of goat lentiviral infection. In addition, our observations support the view that a predominantly humoral (type 2) immune response may contribute to the pathogenesis of CAE.
Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation
Authors: Yanagihara Y , Kajiwara K , Basaki Y , Ikizawa K , Ebisawa M , RA C , Tachimoto H , Saito H 
Published: March 2003

AbstractBy generating human mast cells and basophils from umbilical cord blood mononuclear cells cultured in the presence of appropriate cytokines, we investigated whether these two cultured cells could provide the cytokine and cell contact signals that are required to induce IgE synthesis in B cells. To activate cultured mast cells and basophils, cross-linking of cell surface high-affinity IgE receptor (FcεRI) was performed with specific antigen after sensitization with murine IgE. Upon FcεRI stimulation, basophils, but not mast cells, secreted significant amounts of immunoreactive IL-4 and IL-13 and expressed detectable CD40 ligand (CD40L) and a very low level of Fas ligand (FasL). These observations at the protein level were consistent with the data obtained at the gene transcriptional level, except for the faint expression of only IL-13 mRNA in mast cells. When added to normal human B cells, activated basophils induced IgE and IgG4 synthesis as well as soluble CD23 release. In contrast, neither IgE nor IgG4 synthesis could be induced by the interaction of B cells with activated mast cells, even in the presence of recombinant IL-4. The induction of IgE synthesis by activated basophils was completely abrogated by two neutralizing MoAbs against IL-4 and IL-13 and by a soluble form of CD40. This abrogation was accompanied by abolished mature Cε transcription in both cases. Addition of anti-FasL MoAb, however, did not significantly affect IgE induction mediated by activated basophils. These results demonstrate that unlike cultured mast cells, cultured basophils produce biologically active IL-4 and IL-13 and express functional CD40L after FcεRI stimulation, thereby contributing to IgE production by B cells, and suggest that relatively weak expression of FasL by cultured basophils is not involved in IgE regulation.
Monocytes modulate enhancement of HIV-1 replication byMycobacterium tuberculosis
Authors: De Haas C J C , De Vos N M , Visser M R , Snippe H , Verhoef J 
Published: March 2003

SUMMARYTo investigate the effects of Mycobacterium tuberculosis on HIV-1 replication, peripheral blood mononuclear cells (PBMC) of bacille Calmette–Guérin (BCG)-vaccinated donors and non-BCG-vaccinated donors were infected in vitro with a lymphotropic isolate of HIV-1 and cultured in the presence of purified protein derivative (PPD). Addition of PPD resulted in enhanced HIV-1 replication and lymphoproliferation in BCG-vaccinated donor PBMC, while PPD had no such effects in control PBMC. HIV-1 replication increased even more when monocytes were removed from PBMC, while lymphoproliferation was decreased. High percentages of monocytes were associated with a decreased HIV-1 replication and proliferation that could not be reversed by addition of antibodies against the cytokines IL-1, transforming growth factor-beta (TGF-β) or indomethacin. PPD stimulates PBMC to release IL-10, a cytokine known to down-regulate proliferation and HIV-1 replication. PPD-induced effects on proliferation as well as HIV-1 replication could be partially blocked by adding a monoclonal antibody against MHC class II molecules, suggesting that part of the mechanism of PPD-induced enhancement is T memory cell activation.
Modulation of proinflammatory cytokine production in tumour necrosis factor-alpha (TNF-α)-transgenic mice by treatment with cells engineered to secrete IL-4, IL-10 or IL-13
Authors: Bessis N , Chiocchia G , Kollias G , Minty A , Fournier C , Fradelizi D , Boissier M-C 
Published: March 2003

SUMMARYTNF-α is one of the major proinflammatory cytokines involved in the pathogenesis of chronic inflammatory joint disease, in human rheumatoid arthritis as well as in murine models of this disease. It was previously described that a highly destructive chronic spontaneous inflammatory arthritis develops in mice expressing a human TNF-α transgene modified with the 3′ untranslated region of β-globin. The present study investigates in this mouse model the effects of the anti-inflammatory cytokines IL-4, IL-10 and IL-13 administered in vivo on proinflammatory cytokine expression. Groups of TNF-α-transgenic mice were engrafted with xenogeneic transfected Chinese hamster ovary (CHO) fibroblasts secreting murine IL-4, IL-10 or IL-13. In vivo treatments consisted of 3 or 4 weekly engraftments, starting when the mice were 4 weeks old. Control groups of transgenic mice were engrafted with β-galactosidase gene-transfected CHO cells or injected with medium. A significant decreased expression of TNF-α transgene, endogenous mouse TNF-α and IL-1 mRNA was observed in splenocytes of mice treated for 3 or 4 weeks with CHO/IL-4 and CHO/IL-13, and, to a lesser extent, with CHO/IL-10, compared with controls. Finally, attenuation of histological scores of arthritides was statistically significant only in the group of CHO/IL-4-treated mice after 3 weeks of treatment (P &lt; 0.05), and was not significant in any other group. These results show that IL-4, IL-10 or IL-13, administered by gene therapy, can decrease the mRNA steady state levels of both endogenous and transgenic cytokines in human TNF-α transgenic mice. In addition, IL-4 can slightly attenuate the development of arthritides in this model.
Modifications of general parameters of immune activation in the sera of Sicilian patients with Boutonneuse fever
Authors: Mansueto S , Vitale G , Mocciaro C , Gambino G , Colletti P , Mansueto P , Spinelli A , Affronti M , Chifari N , Arcoleo F , Milano S , Cillari E 
Published: March 2003

SUMMARYThe serum levels of β2-microglobulin (β2-M), soluble HLA class I antigen (sHLA-I), soluble CD4 (sCD4) and CD8 (sCD8) were studied in 98 Sicilian patients with Boutonneuse fever (BF). In different stages of infection all markers were significantly increased in sera from Sicilian patients with acute BF compared with healthy controls. sCD8 and sHLA-I reached the peak in the second week after the onset of symptoms, whereas sCD4 and β2-M reached the peak in the first week. Afterwards sCD8 decreased to the levels of controls within the third week, the other parameters decreased later and were unmodified until the third week of infection. Significant correlations were found between sCD4 and sCD8 and the sIL-2R, as well as between serum levels of β2-M and sCD8. The reduction of CD3+ and CD4+ and the increase of CD8+ T cells in the blood indicate that these cells are involved in the response to rickettsia, and their activation might be in part responsible for the release of sCD4 and sCD8. Our data suggest that these soluble markers, indexes of immune activation of T cells both in the circulation and the affected tissues, may be used in monitoring BF evolution.
Expression of Pax5 gene in human haematopoietic cells and tissues: comparison with immunodeficient donors
Authors: Kaneko H , Ariyasu T , Inoue R , Fukao T , Kasahara K , Teramoto T , Matsui E , Hayakawa S , Kondo N 
Published: March 2003

SUMMARYIn mice, Pax5 gene is indispensable for B cell development. Pax5-deficient mice fail to produce mature B cells owing to complete arrest of B cell development at a precursor stage. However, the lineage and stage of human Pax5 gene expression have remained elusive. In this investigation expression of the human Pax5 gene was studied. Pax5 gene expression was detected in B cell lines but not in myeloma cell lines. CD19 expression was correlated with Pax5 gene expression. Adult spleen and bone marrow and fetal spleen and liver showed strong Pax5 gene expression, as did the corresponding mouse tissues, as reported previously. In common variable immunodeficiency (CVID) peripheral blood lymphocytes (PBL) with a decreased number of B cells, no Pax5 gene expression was detected. Some CVID PBL stimulated with IL-2, IL-10 and anti-CD40 monoclonal antibody, expressed the Pax5 gene. Defect of Pax5 gene expression in CVID may be caused by regulatory T cell disorder.
Cytomegalovirus (CMV) infection in AIDS patients is associated with a CD3 receptor-mediated T cell hyporesponsiveness
Authors: Rowbottom A W , Lepper M W , Sharpstone D , Gazzard B 
Published: March 2003

SUMMARYHIV+ individuals with human CMV (HCMV) reactivation have a CD3 receptor-mediated T cell hyporesponsiveness when compared with CD4-matched HIV+ and HCMV−control groups. The impairment of proliferation was not reversed by exogenous IL-2. A typical increase in NFκB expression was observed following cross-linking of the CD3 receptor, but did not lead to increased CD25 cell surface expression or cell proliferation. The HCMV-induced non-responsiveness was not observed when cells were stimulated with phorbol esters. Lymphocytes cultured with media collected from cell cultures infected with HCMV showed a dose-dependent inhibition in the total T cell population even though cells staining dually for CD8/57 increased in number. The altered growth factor requirements of CD8/57+ cells may therefore account for their presence in AIDS and patients following bone marrow transplantation.
Induction of nitric oxide (NO) synthesis in murine macrophages requires potassium channel activity
Authors: Lowry M A R , Goldberg J I , Belosevic M 
Published: March 2003

SUMMARYThe activation of macrophages for antimicrobial responses is a multistage event involving numerous intracellular signalling cascades that makes possible target cell destruction by these effector cells. This study examined the effects of different potassium channel inhibitors and activators on the NO production of murine macrophage-like cell lines P388D.1 and B10-4(S). We found that the potassium channel inhibitors tetraethylammonium, 4-aminopyridine, and quinine caused dose-dependent reductions in the NO production of macrophages, and that the potassium channel activator, minoxidol, caused a dose-dependent enhancement of NO production. The inhibition of NO production was due to involvement of potassium channels in the priming stage of macrophage activation, since pretreatment with the priming agent interferon-gamma partially restored the NO response of the macrophages. The results of this study demonstrate a link between potassium channel activity and the activation of anitimicrobial functions of murine macrophages.