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J Kips

Publications and source records attributed to J Kips.

At least 19 recordsLinked to original sources
PubMed2001

Distribution of type-1 and type-2 angiotensin receptors in the normal human lung and in lungs from patients with chronic obstructive pulmonary disease.

This study was designed to examine the cellular distribution of the angiotensin II type-1 (AT1) and type-2 (AT2) receptors in the normal human and pathological human lung. Riboprobes were prepared against specific portions of each receptor DNA and labelled with FITC for detection using an anti-FITC antibody in combination with the alkaline phosphatase-anti-alkaline phosphatase technique and new Fuchsin. These were used to detect the presence of receptor mRNA in the lung. Specific antibodies were used to detect receptor protein in cells by immunocytochemistry. Image analysis was used in order to semi-quantify receptor density. AT1 receptor mRNA and protein were localised on vascular smooth muscle cells, macrophages and in the stroma underlying the airways epithelium probably relating to underlying fibroblasts. The AT1 receptor protein was not expressed in the epithelium although there was a low level of mRNA. In contrast, AT2 receptor RNA and protein was observed in the epithelium, with strong staining on the bronchial epithelial cell brush border and also on many of the underlying mucous glands. The AT2 receptor was also present on some endothelial cells. These findings were supported by the presence of mRNA in each case. In patients with chronic obstructive pulmonary disease, there was a five- to sixfold increase in the ratio of AT1 to AT2 receptors in the regions of marked fibrosis surrounding the bronchioles. This correlated well with the reduced lung function as expressed by the forced expiratory volume.

Adult↗
PubMed2000

Update on sputum methodology.

Over the past few years cellular and biochemical sputum examinations have become important instruments to assess airway inflammation. The aim of this review is to summarize new methodological developments and aspects, which are currently under investigation. The use of isotonic saline has increased safety of inductions in patients with severe asthma and in children. The origin of sputum is better understood, as is the need to standardize the volume and duration of induction. It also needs to be borne in mind that the induction procedure itself is able to cause changes in sputum composition. However, the basic induction and processing procedures have not changed much over the last few years, and therefore the method is still time consuming. The analysis of ECP in lysed sputum cells as a marker for the number of eosinophils has been suggested to overcome this problem, but needs further validation. Furthermore, storage of sputum has been studied, as well as early fixation or freezing of sputum cells to elongate the time between induction and processing. Differential cell counts by flow cytometry are still difficult, but the method has increased knowledge concerning lymphocyte subsets and the activation status of sputum cells. The use of induced sputum to noninvasively measure airway inflammation in clinical trials will offer additional information, but the proper use and interpretation of sputum outcome parameters will need further investigation.

Administration, Inhalation↗
PubMed2000

Tissue remodeling as a feature of persistent asthma.

A chronic inflammatory process is almost invariably associated with tissue damage and healing. Healing results in repair and replacement of dead or damaged cells by viable cells. Repair usually involves 2 distinct processes: regeneration, which is the replacement of injured tissue by parenchymal cells of the same type, and replacement by connective tissue and its eventual maturation into scar tissue. In many instances both processes contribute to the healing response. Chronic inflammatory disease can therefore lead to a wide variety of consequences, from complete or partial restitution of organ structure and function to fibrosis. Asthma is characterized by a chronic inflammatory process of the airways. The ensuing healing process results in structural alterations referred to as a remodeling of the airways. The mechanisms underlying these structural alterations are still largely unknown. They are likely to be heterogeneous, leading-through the highly dynamic process of cell de-differentiation, migration, differentiation, and maturation-to changes in connective tissue deposition and to the altered restitution of airways structure, resulting in mucus gland hyperplasia, neovascularization, fibrosis, and an increase in smooth muscle mass.

Asthma↗
PubMed2000

Sequential development of airway hyperresponsiveness and acute airway obstruction in a mouse model of allergic inflammation.

BACKGROUND: Mouse models have been established mirroring key features of human bronchial asthma including airway hyperresponsiveness (AHR). Acute airway obstruction in response to an allergen challenge, however, remains to be demonstrated in these models. OBJECTIVE: A mouse model of allergic lung inflammation was employed to analyze the development of specific (allergen-induced) and nonspecific (methacholine-induced) airway obstruction. METHODS: Mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol twice each week during four weeks. Changes in lung functions were determined by noninvasive head-out body plethysmography. The development of acute airway obstruction after OVA challenge and AHR after methacholine aerosol application were assessed by a decrease in the mid-expiratory flow rate (EF(50)). RESULTS: Two airway challenges were sufficient to induce AHR (5.7 vs. 15 mg/ml methacholine). Further OVA challenges reduced the baseline EF(50) from 1.85 to 1.20 ml/s (4th week) and induced acute airway obstruction. The OVA-induced obstruction was maximal in the 4th week (EF(50) = 0.91 ml/s). CONCLUSION: The development of acute airway obstruction in allergen-sensitized mice was demonstrated by means of head-out body plethysmography. In our model, AHR was observed before the development of airway obstruction.

Airway Obstruction↗
PubMed2000

House dust mite-induced airway changes in hu-SCID mice.

SCID (severe combined immunodeficiency) mice reconstituted with peripheral blood mononuclear cells (PBMC) from Dermatophagoides pteronissynus (Dpt)-sensitive patients and exposed to Dpt aerosol (allergic hu-SCID mice) develop human IgE and pulmonary inflammation. The present study investigated concomitant changes in airway hyperresponsiveness (AHR). No significant difference in baseline airway responsiveness was seen between nonreconstituted SCID mice exposed or not to Dpt aerosol at Day 35. Allergic hu-SCID mice developed AHR (provocative dose of carbachol causing a 50% increase in lung resistance [PD(50) RL] = 96.33 +/- 16.88 microg/kg) compared with nonallergic hu-SCID mice (PD(50) RL = 242.03 +/- 37.84 microg/kg) and nonreconstituted SCID mice (PD(50) RL = 297.60 +/- 45. 60 microg/kg) exposed to Dpt aerosol. An inverse correlation was observed between PD(50) RL (Day 35) and total human IgE at Day 7 (r = -0.58) and Day 15 (r = -0.64). However, no correlation existed between PD(50) RL and human cell number in the lungs of allergic hu-SCID mice. Moreover, despite the absence of eosinophils, the bronchoalveolar lavage fluid (BALF) of allergic hu-SCID mice had more human interleukin-5 (IL-5) (3.28 +/- 0.40 pg/ml, n = 13) than nonallergic hu-SCID mice (< 0.5 pg/ml) which inversely correlated with the PD(50) RL (r = -0.61). No tumor necrosis factor-alpha (TNF-alpha), IL-6, or IL-4 was detected. These observations indicate that humanized allergic hu-SCID mice may develop AHR after exposure to the relevant allergen, suggesting that this model may improve our understanding of AHR, one characteristic feature of allergic asthma.

Airway Resistance↗
PubMed1996

Severity of asthma is related to endotoxin in house dust.

In sensitized subjects, exposure to the mite allergen appears to be only one of several factors leading to asthma. We hypothesized that in association with allergen exposure, endotoxin, a proinflammatory agent present in house dust (HD), influences the severity of asthma. Using a cross-sectional study design, we investigated a group of 69 consecutive dust mite (HDM)-sensitized subjects defined as having rhinitis (n = 20) or asthma (n = 49); the latter were evaluated functionally and clinically by three different scores and by their need for daily medication. Concentrations of Dermatophagoides pteronyssinus p I allergen (Der p I) (by two-site monoclonal antibody enzyme-linked immunosorbent assay [ELISA]), guanine (by high-pressure liquid chromatography [HPLC]), and endotoxin (by modified Limulus. amebocyte lysate assay) were measured in HD collected in duplicate from the mattresses and floors in each subject's home. The concentrations of Der p I and of guanine in HD collected from mattresses were significantly higher in asthmatic subjects than in those with rhinitis (p < 0.05 and < 0.04, respectively). In subjects (n = 37) exposed to a high level of HDM allergen (i.e., Der p I > or = 10 micrograms/g HD and/or guanine > or = 0.10 mg/100 mg HD), the severity of asthma was unrelated to mite allergen concentration in HD. On the contrary, the severity of asthma was related to concomitant exposure to endotoxin in HD, since the concentration of HD endotoxin was significantly and inversely correlated with FEV1 (p < 0.05), FEV1/FVC (p < 0.02), daily need for oral (p < 0.01) and inhaled (p < 0.01) corticosteroids, daily need for beta 2 agonists (p < 0.001) and xanthines (p < 0.01), and clinical scores such as the modified Aas score (p < 0.01). In HDM-sensitized subjects exposed to a high level of allergen, the concentration of endotoxin measured in HD is an important determinant of asthma severity.

Adult↗
PubMed1995

Epidemiology of interstitial lung disease (ILD) in flanders: registration by pneumologists in 1992-1994. Working group on ILD, VRGT. Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding.

Worldwide almost no epidemiologic data are available on the prevalence or incidence of interstitial lung diseases (ILD) in the general population. Therefore, a registration programme of ILD-prevalence was organised by the VRGT (Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding), among about 100 Flemish pneumologists since 1990. Most categories of the classification by Crystal et al. (1) were included and the diagnostic criteria (histology, laboratory tests, clinic, radiology) were registered. The present paper presents the results of 1992-1994: twenty pneumologists had forwarded the summary files of 237 patients to the central office in 1992 (n = 68), 1993 (n = 90) and 1994 (n = 79). The diagnoses that were most frequently made were: sarcoidosis in 27%, idiopathic pulmonary fibrosis in 20%, hypersensitivity pneumonitis in 14% (of which 68% by birds) and collagen-vascular disease in 10% (of which 54% in rheumatoid arthritis). Less frequent causes were eosinophilic pneumonia (4%), inhalation of inorganic material (4%, anthracosilicosis being excluded), histiocytosis X (3%), drugs (3%), angiitis and granulomatosis (2%), pulmonary hemosiderosis (1%), lymphocytic infiltrative lung disease (1%) and lymphangioleiomyomatosis (1%). The order of relative frequencies of the different categories of diseases was the same in the 3 registration years. In 9% of the patients the diagnosis was confined to "undefined fibrosis". The diagnosis was confirmed by histology in 63% of the cases. The overall male-female ratio was nearly one, with, however, a male preponderance in hypersensitivity pneumonitis (22/12), UIP(8/3) and "undefined fibrosis" (14/7).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Allergen-induced airway inflammation and bronchial responsiveness in wild-type and interleukin-4-deficient mice.

T helper 2 (Th2)-like cytokines are thought to play a crucial role in the pathogenesis of airway inflammation in atopic asthma, leading to bronchial hyperresponsiveness. To investigate the role of the principal Th2 cytokine interleukin-4 (IL-4) in asthma, we examined the allergen-induced changes in airway morphology and bronchial responsiveness (BR) in an in vivo mouse model. C57BL/6 mice were actively sensitized to ovalbumin (OVA) and exposed daily to aerosolized OVA or saline (SAL) for 7 days. Twenty-four hours after the last allergen exposure, total and differential counts of bronchoalveolar lavage cells revealed a significant increase of eosinophils and lymphocytes in OVA-exposed immunized mice compared with SAL-exposed animals. In IL-4-deficient (IL-4-/-) mice, treated in the same way, there were substantially fewer eosinophils in bronchoalveolar lavage compared with wild-type mice. Allergen exposure of actively sensitized wild-type mice induced a significant increase of BR to carbachol and to serotonin compared with SAL-exposed mice. In contrast, OVA exposure of immunized IL-4-/- mice did not augment BR to serotonin compared with SAL-challenged IL-4-/- mice. In conclusion, these data indicate that repeated allergen exposure in sensitized mice induces airway inflammation and bronchial hyperresponsiveness, and that IL-4 plays a predominant role in the pathogenesis of both phenomena.

Allergens↗
PubMed1990

Airway hyperreactivity, an introduction.

Asthma is characterized by the presence of airway inflammation and an increased responsiveness to many different stimuli. The hyperresponsiveness to indirect stimuli such as adenosine, bradykinin, neuropeptides, sulphur dioxide suggest that the hyperresponsiveness in asthma results from the complex interaction between inflammatory cells, neurons and smooth muscle cells. Several mechanisms may be involved in the influence of airway inflammation on airway responsiveness: increased mucosa permeability: enhanced exposure of irritant receptors, modulation of airway smooth muscle behavior by inflammatory mediators, mucosal edema, enhanced release of neurotransmitters, increased local reflex activity, decreased breakdown of neurotransmitters, etc. We have investigated the interaction between airway inflammation and responsiveness in two animal models: acute exposure to endotoxin and chronic exposure to aerosolized antigen. Both models demonstrate the complexity of interaction between inflammatory processes and demonstrate positive controlling mechanisms that inhibit the increase in airway responsiveness due to airway inflammation. The lack of such controlling mechanisms may be involved in the development of the asthmatic airway hyperresponsiveness.

Administration, Inhalation↗
PubMed1986

The effect of tachykinins on the conducting airways of the rat.

We studied the bronchial effects of intravenously administered tachykinins in inbred rats. Substance P and related tachykinins caused a dose-dependent bronchoconstriction. The bronchial reactivity to substance P differed significantly between different inbred rat strains. Substance K, eledoisin and kassinin were more potent than substance P in causing bronchoconstriction. This suggests a predominance in the bronchi of SP-E receptors. The bronchial effects of substance P and eledoisin were largely inhibited by atropine and slightly enhanced by hexamethonium. In addition to a direct effect on airway smooth muscle, tachykinins interfere with the cholinergic airway innervation of the rat at the ganglionic and postganglionic level.

Airway Resistance↗
PubMed1986

The respiratory effects of neuropeptides.

Several peptides have been localised to pulmonary nerves and endocrine cells. The neuropeptides vasoactive intestinal polypeptide (VIP) and substance P have potent effects on the airway smooth muscle, bronchial glands and blood vessels. There is increasing evidence that VIP and substance P are neurotransmitters of the non-adrenergic, non-cholinergic nervous (NANC) system. Non-adrenergic inhibitory nerves are the predominant inhibitory nervous system of the human airways. The presence of VIP in the innervation of the airways and the demonstration that it can mimick the effect of NANC nerve stimulation supports the hypothesis that it could be a mediator of the NANC system in the lungs. Sensory nerve fibers containing substance P can contribute to the smooth muscle contraction and mucosal oedema seen in asthma, by local axon reflexes that are initiated by noxious stimuli, such as for example cigarette smoke. A rat model for study of the bronchial reaction to substance P and related tachykinins, is described. In addition to a direct effect on airway smooth muscle, a large part of the broncho-constrictory actions of tachykinins in the rat is mediated by interaction with cholinergic nerves.

Airway Resistance↗
PubMedDate not supplied

Demonstration of the therapeutic potential of non-anaphylactogenic anti-IgE antibodies in murine models of skin reaction, lung function and inflammation.

BACKGROUND: Allergies and allergic asthma are believed to be mediated by allergen-specific IgE antibodies. We have investigated the therapeutic potential of inhibiting endogenous IgE by a non-anaphylactogenic anti-mouse IgE antibody 1-5 with respect to its effects on antigen-induced skin reaction, lung function changes and lung inflammation in mice. METHODS: Mice were immunized with benzylpenicillinoyl-KLH or ovalbumin, and antigen-mediated skin reaction, bronchoconstriction, bronchopulmonary hyperresponsiveness (BHR) and lung eosinophilic inflammation determined in anti-IgE 1-5-treated versus untreated animals. RESULTS: Application of anti-IgE 1-5 inhibited (by 90%) the serum IgE and, 3-4 days after onset of treatment, blocked the antigen-induced skin reaction. Furthermore, the antibody also inhibited (by 90%) the antigen-induced infiltration of eosinophils into the lung. This latter effect seems to be mediated by blocking the IgE-CD23 interaction and indicates that lung eosinophilic inflammation also depends on IgE. Moreover, when applied to rats passively sensitized with mouse IgE, antibody 1-5 inhibited the antigen-induced bronchoconstriction. A similar effect could be seen in actively immunized mice, where antibody 1-5 was able to inhibit (by 70%) the ovalbumin-induced bronchoconstriction as well as BHR. CONCLUSIONS: In summary, non-anaphylactogenic anti-IgE antibodies can markedly inhibit IgE levels and IgE-mediated allergic reactions. Since bronchoconstriction, BHR and lung eosinophilic inflammation can be suppressed, such antibodies may be attractive principles for the treatment of allergic asthma.

Animals↗