bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluticasone propionate and mometasone furoate have equivalent transcriptional potencies
Authors: Roumestan C. , Henriquet C. , Bousquet J. , Mathieu M. 
Published: July 2003

SummaryBackground
Glucocorticoids exert their anti‐inflammatory effects mainly through transrepression of the transcription factors activator protein‐1 (AP‐1) and nuclear factor‐kappa B (NF‐κB). Certain adverse effects of glucocorticoids are mediated through gene transactivation. Fluticasone propionate (FP) and mometasone furoate (MF) are the most recently developed topical glucocorticoids for the treatment of airway disorders. Their relative capacities to repress AP‐1 and NF‐κB activities are not known and comparison of their transactivation potencies has given unclear results.Objective
To determine the relative transactivation and transrepression potencies of FP and MF.Methods
Transactivation assays were performed in HeLa cells carrying a glucocorticoid‐inducible luciferase gene. To measure transrepressive potencies of FP and MF, A549 lung epithelial cells were transiently transfected with an AP‐1‐ or NF‐κB‐dependent luciferase gene. Using an immunoassay, we also evaluated the ability of MF and FP to inhibit the production of Regulated upon Activation, Normal T‐cell Expressed and Secreted (RANTES), a pro‐inflammatory cytokine, whose gene is controlled by AP‐1 and NF‐κB. Areas under the dose–response curve were calculated to determine relative potencies.Results
FP and MF are equipotent for transactivation. Both molecules show globally the same potency to inhibit AP‐1 and NF‐κB activities and RANTES production. MF and FP have very significant transcriptional effects at 2×10−10 M, which is the peak concentration reached in the plasma after inhalation of high dosages. Indeed, they produce a 17‐fold induction of luciferase in the transactivation assay, and inhibit AP‐1 activity, NF‐κB activity and RANTES release by approximately 40%.Conclusion
FP and MF have the same ability to trigger gene activation and also the same potency to inhibit AP‐1 and NF‐κB activities. Their strong transcriptional effects at 2×10−10 M suggest that these compounds act not only topically but also systemically, with the risk of provoking concomitant adverse effects at high dosages.
Reducing agents inhibit the contractile response of isolated guinea‐pig main bronchi
Authors: Casoni G. L. , Chitano P. , Pinamonti S. , Chicca M. , Ciaccia A. , Fabbri L. , Papi A. 
Published: July 2003

SummaryBackground
Oxidants are involved in many respiratory disorders, including asthma and chronic obstructive pulmonary diseases. Reduced glutathione (GSH), one of the most important antioxidant compounds against oxidant free radicals, is particularly abundant in the respiratory epithelial lining fluid, where its concentration is increased in inflammatory disorders.Objective
We hypothesized that reducing agents may have a direct effect on airway smooth muscle. Therefore, we studied the effects of GSH on airway smooth muscle contractility in guinea‐pig main bronchi. In parallel, we evaluated superoxide anion generation associated with in vitro bronchial smooth muscle contraction.Methods
Guinea‐pig main bronchi were mounted in organ baths filled with Krebs–Henseleit solution. Concentration–response curves to acetylcholine (Ach) (10−9–10−3 M), carbachol (10−9–10−4 M), or histamine (10−9–10−3 M) were performed in the presence or absence of either reduced or oxidized glutathione (GSSG) (10−5–10−3 M). We also evaluated the effects of GSH and GSSG on allergen‐induced contraction in main bronchi obtained from ovalbumin‐sensitized guinea‐pig. Superoxide dismutase (SOD)‐inhibited cytochrome c reduction kinetics was performed to evaluate superoxide anion (O2−) production during Ach‐induced contraction.Results
Reduced but not oxidized glutathione significantly decreased smooth muscle contraction induced by Ach, carbachol, and histamine. Similarly, only the reduced form of glutathione attenuated the bronchoconstriction induced by allergen exposure in bronchi from sensitized animals. Finally, SOD‐inhibited cytochrome c reduction kinetics demonstrated increased O2− production following bronchial smooth muscle contraction. This production was not affected by epithelium removal.Conclusion
Our findings show that GSH decreases bronchial smooth muscle contraction to different stimuli and that oxidant free radicals are produced during bronchial smooth muscle contraction. We suggest that oxidants are involved in the mechanisms of bronchoconstriction and that reducing agents could be a possible therapeutic option for airway obstruction sustained by bronchospasm.
An adult model of exclusive viral wheeze: inflammation in the upper and lower respiratory tracts
Authors: Mckean M. C. , Hewitt C. , Lambert P. C. , Myint St. , Silverman M. 
Published: July 2003

SummaryBackground
We have previously reported an experimental infection of young adults with a history of episodic and exclusive viral wheeze (EVW) using human coronavirus, in which 16 of 24 with EVW (15 atopic) and 11 of 19 healthy controls (seven atopic) developed a symptomatic cold with evidence of infection, but only those with EVW developed lower respiratory tract symptoms and increased airway responsiveness.Objective
The aim of this study was to compare the EVW and control groups from this study for inflammatory changes occurring in the upper and lower respiratory tracts during the experimental infection, in particular, to determine whether eosinophil‐driven inflammation was associated with EVW.Methods
Nasal lavage and induced sputum were collected prior to inoculation (day 0) and 2, 4 and 17 days later. Differential cell counts were performed and supernatant was assayed for IL‐8, IL‐5, IFN‐γ, and eosinophilic cationic protein (ECP).Results
There was no difference between the two groups in any measurement at baseline. In both groups, during colds the volume of nasal secretion increased as did leucocyte counts in both upper and lower respiratory tracts. A modest increase in nasal neutrophil count was seen in both EVW and control groups with symptomatic colds on day 2 (median (quartile) difference from baseline 5.4 (0.0, 11.0) and 1.8 (−1.1, 2.2)×104/mL of secretions, respectively). The change in nasal neutrophil counts in all subjects correlated with nasal symptom scores. A significant relative increase in sputum differential neutrophil count was seen on day 4 in the EVW group with a cold but not in controls (mean difference (95% confidence interval) 20.4 (9.6, 31.1)% and 3.1 (−8.2, 14.5)%, respectively, P<0.01); however, this increase did not correlate with lower respiratory tract symptom scores. IL‐8 increased in both the upper and lower respiratory tracts in both EVW and control subjects with colds, the largest change being seen on day 4 in the sputum of those with EVW (mean difference from baseline (95% confidence interval) 2.5 (0.55–4.46) ng/mL). Only modest changes were seen in IFN‐γ and no changes were seen in IL‐5 or ECP. None of the results was influenced by the atopic status of the subjects in either group.Conclusions
EVW wheeze is characterized by neutrophilic inflammation in both the upper and lower respiratory tracts without eosinophilia (even in atopic subjects). IL‐8 is likely to be an important chemokine in this process. Symptoms and airway responsiveness were correlated with change in neutrophils.
Mechanisms in cutaneous drug hypersensitivity reactions
Authors: Friedmann P. S. , Lee M.‐S. , Friedmann A. C. , Barnetson R. St C. 
Published: July 2003

SummaryUp to 3% of all hospital admissions are due to adverse drug reactions (ADRs), and between 10% and 20% of hospital inpatients develop ADRs. Individual susceptibility to becoming ‘sensitized’ or allergic to a drug is thought to result from altered metabolic handling of the drug. Reactive intermediate compounds form haptens, bind to proteins and induce immune responses. Depending on whether the immune system generates antibodies or sensitized T cells, different clinical patterns of hypersensitivity may result. At present, both in vivo or in vitro tests to identify the culprit drug or to confirm the presence of hypersensitivity are not widely used because they are either not generally robust or not readily accessible. In vitro tests require the true immunogen/antigen to detect antibodies or sensitized T cells. As the metabolic basis underlying susceptibility to adverse drug reactions is elucidated, the resolution of immunological mechanisms and development of reliable tests will ensue. This will also become of great value for prediction of individuals at risk of becoming sensitized by a particular drug.
Localization and content of nerve growth factor in peripheral blood eosinophils of atopic dermatitis patients
Authors: Toyoda M. , Nakamura M. , Makino T. , Morohashi M. 
Published: July 2003

SummaryBackground  Atopic dermatitis (AD) is a chronic and relapsing eczematous skin disorder characterized by eosinophilia. Nerve growth factor (NGF) modulates the allergic response through interactions with immune‐inflammatory cells. Eosinophils have been reported to store NGF as a preformed mediator.Objective  To gain further insight into the significance of eosinophils in association with NGF in the pathogenesis of AD, the localization of NGF within eosinophils and the difference of the eosinophil‐derived NGF content in the peripheral blood of normal volunteers vs. AD patients were investigated.Methods  We examined the localization of NGF within human eosinophils using the post‐embedding immunoelectron microscopy and compared NGF content in freshly isolated eosinophil sonicates from the peripheral blood of 31 normal volunteers vs. 42 AD patients by immunoenzymatic assay. A possible correlation between the levels of NGF and major basic protein was also examined.Results  Immunoelectron microscopic studies revealed that NGF was localized in the central core of normal eosinophil granules, where major basic protein is also present as a preformed mediator, in homogeneous granules and in intergranular ductal or vesicular structures adjacent to specific granules of eosinophils. NGF content in eosinophils was significantly increased in AD patients. Furthermore, there was a significant correlation between levels of NGF and major basic protein in eosinophils of AD patients.Conclusions  Increased levels of NGF contained in eosinophils of the peripheral blood from AD patients, when released with other mediators such as basic proteins, could promote inflammation and local tissue damage.
Purification and characterization of mouse mast cell proteinase‐2 and the differential expression and release of mouse mast cell proteinase‐1 and ‐2 in vivo
Authors: Pemberton A. D. , Brown J. K. , Wright S. H. , Knight P. A. , McPhee M. L. , McEuen A. R. , Forse P. A. , Miller H. R.P. 
Published: July 2003

SummaryBackground
Gastrointestinal nematode infection is associated with mucosal mast cell (MMC) hyperplasia. In the mouse, this is accompanied by the release of substantial quantities of the chymase mouse mast cell proteinase‐1 (mMCP‐1) into the gut lumen and peripheral bloodstream. Expression of mMCP‐1 is largely restricted to intraepithelial MMC and is thought to play a role in the regulation of epithelial permeability. MMCs also express mouse mast cell proteinase‐2 (mMCP‐2), but less is known about the expression or biological function of this proteinase.Objectives
(1) To purify and characterize mMCP‐2. (2) To compare the expression and release of mMCP‐2 and mMCP‐1 in vivo using specific antibodies.Methods
Bone marrow‐derived mast cells (mBMMCs) were generated from mMCP‐1−/− BALB/c mice. mMCP‐2 was purified, characterized and used to generate rat and sheep polyclonal antibodies. The expression and systemic release of mMCP‐1 and ‐2 were compared in vivo by immunohistochemistry and ELISA.Results
mMCP‐2 was successfully purified from mMCP‐1−/− mBMMC and its identity confirmed by N‐terminal amino acid sequencing. mMCP‐2 bound [3H]‐labelled DFP, indicating the presence of an active serine proteinase catalytic site, but showed little evidence of chymotryptic activity. MMC expressed comparable levels of mMCP‐1 and ‐2 in the jejunum but not in the gastric mucosa, where mMCP‐2 was more abundant. Expression of both proteinases increased substantially during primary Nippostrongylus brasiliensis infection and this was accompanied by a substantial increase in peripheral blood levels of mMCP‐1 (70 μg/mL on day 12). By contrast, mMCP‐2 was not detected in the serum of uninfected mice and only increased to approximately 25 ng/mL on day 12.Conclusion
As in the case of mMCP‐1, mMCP‐2 expression is restricted to MMC. However, mMCP‐2 lacks chymase activity, is expressed at higher levels in gastric MMC and appears to be differentially released into the peripheral bloodstream.
Pituitary adenylate cyclase‐activating polypeptide, effects in the human nose
Authors: Kinhult J. , Adner M. , Uddman R. , Cardell L. O. 
Published: July 2003

SummaryBackground  Pituitary adenylate cyclase‐activating peptide (PACAP) is a neuropeptide with strong vaso‐ and bronchodilator capacity. There is recent evidence that PACAP decreases the release of proinflammatory cytokines and we have previously shown that PACAP inhibits neutrophil chemotaxis in vitro, but little is known about the effects of PACAP in human upper and lower airways.Objective  To investigate the effects of PACAP in the human upper respiratory tract focusing on vasodilatation/nasal airway resistance (NAR), neutrophil recruitment, plasma extravasation and endogenous production of IL‐1‐related mediators.Methods  Surgical specimens from five patients (aged 19–55 years), obtained in conjunction with nasal surgery, were used for immunohistochemical localization of PACAP in the nasal mucosa. In seven, healthy, non‐allergic, non‐smoking subjects (aged 19–45 years), NAR was measured with rhinomanometry. Nasal lavage was performed, before and after intranasal application of PACAP (200 μL of a 1 μm PACAP solution in each nasal cavity), with and without the addition of histamine. Cells, albumin and IL‐1‐related mediators were analysed in nasal lavage. In addition, the effects on pulse, blood pressure, ECG and pulmonary function were evaluated.Results  In the nasal mucosa, PACAP‐like immunoreactive nerve fibres were seen close to blood vessels and seromucous glands. Application of PACAP in the nasal cavity increased NAR and augmented the increase in NAR induced by histamine. In addition, PACAP inhibited histamine‐induced recruitment of neutrophils, increased plasma leakage and reduced the level of IL‐1RA (an endogenously produced IL‐1 receptor antagonist) in nasal lavage. Cardiovascular and pulmonary parameters were not affected.Conclusion  These results imply that PACAP is an important endogenous mediator in human upper airways, with a potential role as a regulator of vascular smooth muscle, secretion, plasma extravasation, neutrophil recruitment and cytokine activity.
Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomyosin, in unexposed Orthodox Jews
Authors: Fernandes J. , Reshef A. , Patton L. , Ayuso R. , Reese G. , Lehrer S. B. 
Published: July 2003

SummaryBackground
Assessment of allergic (IgE antibody‐mediated) reactions to foods may become complicated by cross‐reactivity that can occur among certain food families and between foods and seemingly unrelated allergens.Objective  The allergenic properties of tropomyosin (muscle‐derived protein) have been recently demonstrated in invertebrates such as cockroaches, dust mites, and shrimp. In view of a possible cross‐reactivity between food allergens and related allergens from animal sources, we designed a study to assess IgE antibody reactivity to the major shrimp allergen, Pen a 1, in an unexposed population of Orthodox Jews, who observe Kosher dietary laws that prohibit eating shellfish.Methods
Nine subjects, who reacted positively by skin tests to shrimp (Penaeus setiferous), were selected for the study. Subjects (two females, seven males) ranged in age from 14 to 32 years (mean 20.4). All subjects were strictly observant of Jewish tradition and had no prior exposure to seafood (regarded as a non‐Kosher food). Serum was obtained from all the subjects and tested for IgE antibody reactivity to shrimp and dust mite.Results
All subjects reported symptoms of perennial allergic rhinitis, five had history of asthma, atopic dermatitis, and/or sinusitis. All had positive skin prick tests to shrimp and house dust mite (HDM) (Dermatophagoides farinae, D. pteronyssinus, or both); 2/7 subjects were positive to cockroach mix (Blattella germanica and Periplaneta americana). Sera of 4/9 subjects demonstrated specific IgE antibodies by RAST to shrimp (7.0–20.0%), 3/9 to Pen a 1 (6.3–24.1%), and 3/9 to shrimp or Pen a 1 by immunoblot. IgE binding to Pen a 1 was inhibited with either mite or cockroach extracts as demonstrated by RAST and/or immunoblot inhibition analysis.Conclusions
These studies indicate that IgE antibody reactivity to a major food allergen, shrimp, can occur in an unexposed population of individuals; some subjects allergic to HDM and/or cockroach show substantial IgE antibody reactivity to the major shrimp allergen Pen a 1 (tropomyosin). Based on inhibition with cockroach and/or dust mite extracts, this reactivity appears to be due to cross‐reacting tropomyosins.
Complement component C7 deficiency in a Spanish family
Authors: VÁZQUEZ-BERMÚDEZ M F , BARROSO S , WALTER K , ÁLVAREZ A J , ALARCÓN A , LÓPEZ-TRASCASA M , WICHMANN I , AGUILAR F , NÚÑEZ-ROLDÁN A , SÁNCHEZ B 
Published: July 2003

SUMMARYDifferent genetic mutations have been described in complement component C7 deficiency, a molecular defect which is clinically associated with an increased susceptibility to neisserial recurrent infections, although some cases remain asymptomatic. In this work we report the genetic bases of C7 deficiency in one Spanish family. Exon-specific PCR and sequencing revealed a novel point mutation at nucleotide 615 (exon 6) leading to a stop codon (UGG to UGA) in the patient, his mother, and sister. This transversion causes the premature truncation of the C7 protein (W183X). Additionally, we detected a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in an amino acid change (G357R) in the patient, his father, as well as in his sister. This latter mutation had been previously described in individuals from Moroccan Sephardic Jewish ancestry. Since both heterozygous mutations were found in the patient as well as in his asymptomatic sister, we analyse other meningococcal defence mechanisms such as polymorphisms of the opsonin receptors on polymorphonuclear cells. Results showed that the patient and his sister bore identical combinations of FcγRIIA-H/R131 and FcγRIIIB-NA1/2 allotypes. Our results provide further evidence that the molecular pathogenesis of C7 deficiency as well as susceptibility to meningococcal disease are heterogeneous, since different families carry different molecular defects, although many of the C7 defects appear to be homogeneous in individuals from certain geographical areas. The missense mutation G357R would make an interesting topic of analysis with regard to meningococcal disease susceptibility in the Spanish population.
IgA class antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis and autoimmune hepatitis
Authors: SCHWARZE C , TERJUNG B , LILIENWEISS P , BEUERS U , HERZOG V , SAUERBRUCH T , SPENGLER U 
Published: July 2003

SUMMARYAntineutrophil cytoplasmic antibodies (ANCA) of IgG class have been described at high prevalence in autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Data on IgA class ANCA in these diseases are limited. The aim of this study was to determine the prevalence and fluorescence patterns of IgA class ANCA in AIH and PSC and to examine a relationship between the presence of IgA ANCA and clinical characteristics in these patients. Sera from 35 patients with PSC (21 with concomitant inflammatory bowel disease), 40 patients with AIH and 10 healthy controls were studied. ANCA were detected on ethanol-fixed neutrophils using an indirect immunofluorescence technique. ANCA of the IgA class were found in 20% of sera from patients with PSC and in 50% of AIH sera. The majority of AIH patients with IgA class ANCA showed a ‘classical’ perinuclear staining pattern, whereas the ‘classical’ and ‘atypical’ perinuclear fluorescence patterns were distributed equally in PSC. In sera containing IgG and IgA class ANCA simultaneously, IgG class ANCA showed an ‘atypical’ pANCA fluorescence pattern whereas IgA class ANCA produced a ‘classical’ perinuclear staining. The presence of IgA class ANCA was not associated with disease-specific clinical characteristics. IgA class ANCA are more frequently detected in sera of patients with AIH than PSC. The diversity of fluorescence patterns points to different target antigens of IgA class ANCA with distinct subcellular localizations.
IL-16 in the airways of lung allograft recipients with acute rejection or obliterative bronchiolitis
Authors: LAAN M , LINDÉN A , RIISE G C 
Published: July 2003

SUMMARYAcute rejection (AR) is the principal risk factor for obliterative bronchiolitis (OB), the major complication of lung transplantation. It is known that activated CD4+ T lymphocytes are involved in the development of AR and that interleukin (IL)-16 can inhibit the activity of CD4+ T lymphocytes. In this study, we evaluated whether the concentration of IL-16 in the airways is altered in AR or OB and, if so, how this IL-16 concentration relates to the number or activity of airway lymphocytes. The concentration of IL-16 protein was measured in bronchoalveolar lavage (BAL) fluid at three time-points in lung allograft recipients with either AR or OB and in matched controls using ELISA. The concentration of soluble IL-2 receptor (R) protein was measured in BAL fluid using ELISA as well, as an indicator of lymphocyte activity. The percentage of airway lymphocytes was evaluated by performing BAL differential cell counts. Lung allograft recipients with AR displayed lower IL-16 concentrations compared with matched control patients and this IL-16 concentration correlated negatively with the sIL-2R concentration, but it did not correlate with the percentage of lymphocytes in BAL fluid. In contrast, in BAL fluid from lung allograft recipients with OB, the IL-16 concentration was not altered compared with matched control patients and it did not correlate with the percentage of lymphocytes or with the sIL-2R concentration. These data are compatible with an increase in IL-16 playing a protective role against AR but not against OB and, hypothetically, this type of protective effect could be exerted via a down-regulation of the activity of T lymphocytes.