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Biomedical subjects

M L Kowalski

Publications and source records attributed to M L Kowalski.

At least 19 recordsLinked to original sources

Endocrine disrupters--potential modulators of the immune system and allergic response.

Endocrine disrupters (EDs) are environmental pollutants of industrial or agricultural origin (e.g. herbicides, fungicides, insecticides, industrial chemicals) that may influence health of wildlife and human. Endocrine-disrupting effect is obtained by mimicking the action of the steroid hormones and has been associated with several reproductive disorders as well as cancerogenesis both in animals and humans. EDs can also influence synthesis of cytokines, immunoglobulins, and cell mediators as well as immune cell activation and survival. Modulation by EDs of interleukin-4 production, Th1/Th2 balance and IgE production suggest their potential effect on allergic immune responses. The aim of this review was to summarize data indicating a potential effect of EDs exposure on the immune system and allergic responses.

Endocrine System↗

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗

Tissue remodelling in upper airways: where is the link with lower airway remodelling?

Tissue remodelling reported in upper airways include epithelial hyperplasia, increased matrix deposition in the nasal or paranasal lining, matrix degradation and accumulation of plasma proteins. Genetic influences, foetal exposures and early life events may contribute to structural changes such as subepithelial fibrosis from an early age. Other structural alterations are related to duration of the disease and long-term uncontrolled inflammation. Structural changes may increase alteration of the protective functions of the upper airways namely by affecting mucociliary clearance and conditioning of inspired air. The sequences of tissue changes during wound repair of upper airway mucosa after surgery are illustrative of the complexicity of tissue modelling and remodelling and could be considered as an important source of information for a better understanding of the complex relationship between inflammatory reaction, of the subsequent tissue damages and fibroblast metabolism of upper airways.

Animals↗

Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine.

Nasal polyp tissue which contains mast cells and eosinophils is similar to the inflamed airway mucosa in cellular composition and mediator content. This investigation assessed the effect of desloratadine (DL), on activation of cells in nasal polyp tissue. Polyps were obtained from 22 patients with chronic rhinosinusitis [nine aspirin acetylosalitic acid (ASA)-sensitive and 13 ASA-tolerant]. Polyp tissue was dispersed by digestion, and preincubated with DL and incubated with anti-immunoglobulin E (IgE) or calcium ionophore. LTC4, eosinophil cationic protein (ECP) and tryptase concentrations in supernatants were measured by immunoassays. Desloratadine (1, 10 and 50 microM) inhibited calcium ionophore-induced LTC4 release by a mean of 29%, 50% and 63% respectively, and anti-IgE-induced LTC4 release by a mean of 27%, 35% and 39% respectively. Calcium ionophore-induced tryptase release was inhibited 60% and 69% by 10 and 50 microM of DL, respectively, and anti-IgE-induced tryptase release was inhibited 33%, 47% and 66% for 1, 10 and 50 microM of DL. Desloratadine 10 microM and 50 microM inhibited ECP release by and 45% and 48% respectively. Polyp tissue from ASA-sensitive patients when compared with ASA-tolerant patients released at baseline significantly more ECP (medians 120.0 microg/ml, range: 69.0-182.0 vs 63.4 microg/ml, range: 3.7-172.0; P <0.05), but similar amounts of tryptase and LTC4. This study demonstrated that DL inhibits activation of both eosinophils and mast cells derived from a site of airway mucosal inflammation.

Adult↗

Association of stem cell factor expression in nasal polyp epithelial cells with aspirin sensitivity and asthma.

Mast cells constitute a significant proportion of cells infiltrating nasal polyp tissue, and epithelial cells may release stem cell factor (SCF), a cytokine with chemotactic and survival activity for mast cells. We aimed to assess the expression of SCF in human nasal polyp epithelial cells (NPECs) as related to patients' clinical phenotypes. Nasal polyp tissues were obtained from 29 patients [including nine with aspirin (ASA)-hypersensitivity and 12 with bronchial asthma] undergoing polypectomy for nasal obstruction. Epithelial cells were obtained following 6-week culture of nasal polyps explants. The SCF released into the culture supernatant was assessed by enzyme-linked immunosorbent assay (ELISA) and total SCF mRNA in the polyp tissue was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). For the whole group of patients, the number of polypectomies correlated with expression of SCF mRNA (r = 0.62; P < 0.005), SCF protein in the NPECs supernatants (r = 0.39; P < 0.05) and with density of mast cells in epithelial layer (r = 0.37; P < 0.05) and stromal layer (r = 0.5; P < 0.01) of nasal polyps. The SCF/beta-actin mRNA ratios were significantly higher in ASA-hypersensitive (AH) asthmatics (median 0.97, range: 0.8-1.5) when compared with ASA-tolerant (AT) patients (median 0.5, range: 0.1-0.7; P < 0.001). The SCF protein concentration in NPEC supernatants was also significantly higher in AH asthmatics (median 1.10 pg/microg DNA, range: 0.4-1.9) when compared with AT patients (median 0.1 pg/microg DNA, range: 0.02-1.2; P < 0.001). In the subpopulation of ASA-sensitive asthmatics the number of polypectomies correlated also with the density of mast cells and eosinophils in the polyp tissue.

Adult↗

Aspirin-triggered 15-HETE generation in peripheral blood leukocytes is a specific and sensitive Aspirin-Sensitive Patients Identification Test (ASPITest).

BACKGROUND: We have previously demonstrated that aspirin triggers specific generation of 15-hydroxyeicosateraenoic acid (15-HETE) from nasal polyp epithelial cells and peripheral blood leukocytes (PBL) from aspirin-sensitive (AS) but not aspirin-tolerant (AT) patients with asthma/rhinosinusitis. The goal of this study was to assess the diagnostic value of ASA-induced 15-HETE generation measurement to identify AS patients. METHODS: PBL were obtained from 43 AS patients with asthma and rhinosinusitis, 35 AT asthmatics and 17 healthy control (HC) subjects. PBL were incubated with 2-200 muM aspirin (ASA) and 15-HETE release was measured in cell supernatants with competitive ELISA. RESULTS: Unstimulated PBL from all three groups of patients generated similar amount of 15-HETE. Incubation with 200 microM ASA resulted in an increase in an 15-HETE generation (mean increase +421%) in AS-asthmatics but small and nonsignificant response in AT-asthmatics or control subjects. Receiver operating curve (ROC) analysis revealed that the sensitivity of the test for confirmation of ASA-sensitivity was 83% and the specificity 82%. Positive predictive value was 0.79 and negative predictive value was 0.86. Naproxen induced a significant increase in 15-HETE only in some AS-asthmatics, but not in AT-asthmatics. CONCLUSION: Our data demonstrate that ASA-induced 15-HETE generation by PBL is a specific and sensitive aspirin-sensitive patients identification test (ASPITest).

Adult↗

Beta2-ADR haplotypes/polymorphisms associate with bronchodilator response and total IgE in grass allergy.

Association and linkage studies of beta2-adrenergic receptor (beta2-ADR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. In order to analyse the relevance of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of beta2-ADR gene to bronchial asthma, bronchodilator response and total immunoglobulin E (IgE) we determined by direct DNA sequencing five SNPs (in positions: -47, -20, 46, 79, 252) in a group of 180 Caucasian subjects (110 patients with grass allergy and 70 nonatopic controls). The eight different beta2-ADR haplotypes were identified, with three the most common of them representing 92% of the studied cohort. Significantly higher (pcor = 0.0045) bronchodilator response was observed in patients with homozygotic genotype 46A/A in comparison with respective homo- and hetero-zygotes. There was no significant difference in bronchodilator response when beta2-ADR haplotypes were analysed. Significantly higher (pcor = 0.0005) total IgE levels were found in patients with beta2-ADR haplotype -47T/-20T/46A/79C/252G and homozygotic carriers of 46A (pcor = 0.0015) and 79C (pcor = 0.003) genotypes. No significant associations were found in regards to asthmatic phenotype and atopy. These results indicate that depending on phenotype studied, either an individual beta2-ADR SNP or beta2-ADR haplotype might affect disease manifestation.

Adult↗

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.

Administration, Inhalation↗

Decreased apoptosis and distinct profile of infiltrating cells in the nasal polyps of patients with aspirin hypersensitivity.

BACKGROUND: Patients with aspirin-hypersensitive rhinosinusitis/asthma suffer from a severe form of hyperplastic rhinosinusitis with recurrent polyposis. We aimed to assess the presence of apoptotic cells in nasal polyps from aspirin-hypersensitive (AH) and aspirin-tolerant (AT) patients with rhinosinusitis as related to the characteristics of local inflammation. METHODS: Nasal polyps obtained from 16 AH patients and 36 AT patients (17 atopic and 19 nonatopic) were stained for eosinophils and metachromatic cells, and in parallel immunocytochemistry was performed to detect CD45RO+, HLA-DR+, CD8+ and CD68+ positive cells. Apoptotic cells were detected by a nick-end labelling technique, TUNEL. RESULTS: The density of apoptotic cells in AH polyps (5.5 + 1.5 cells/mm2) was significantly lower as compared to both atopic (18.7 + 3.8 cells/mm2; P < 0.02;) and nonatopic (21.3 + 5.2 cells/mm2; P < 0.01) AT polyps. The number of eosinophils, mast cells, and CD45RO+ cells were significantly increased in AH compared to AT polyps (P < 0.001), and the density of HLA-DR+ cells in AH patients was higher than in nonatopic (P < 0.02), but not in atopic AT patients. While in AH patients the duration of rhinosinusitis correlated inversely with the number of apoptotic cells (r = - 0.67; P < 0.04), in contrast, in AT atopic patients the duration of rhinosinusitis showed positive correlation with apoptosis (r = 0.89; P < 0.003). CONCLUSIONS: We conclude, that decreased apoptosis of inflammatory cells in nasal polyps from ASA-hypersensitive patients, reflects a distinct mechanisms of local inflammation and may be related to persistence and severity of the disease in these patients.

Adult↗

Association of asthma and total IgE levels with human leucocyte antigen-DR in patients with grass allergy.

Exposure to grass pollens during the pollen season, reveals in sensitive patients symptoms of allergic rhinitis, conjunctivitis and/or bronchial asthma. It is not well understood why, in some patients, only symptoms of rhinitis occur while in others similar exposure causes symptoms of asthma and rhinitis. An association study is reported here, where the possible contribution of human leucocyte antigen (HLA)-DR gene polymorphisms to differential phenotypic expression of symptoms in patients with grass-pollen allergy was determined. HLA-DR genotyping was performed by the polymerase chain reaction with the sequence-specific primers method in 82 patients with symptoms of seasonal allergic rhinitis and/or bronchial asthma and 52 healthy nonatopic control subjects. A significant association was found between HLA-DRB1*02, B5* haplotype and asthma phenotype in patients with grass-pollen allergy when compared to patients with rhinitis only. Significantly higher total serum immunoglobulin E levels were observed in patients with HLA-DRB1*01 alleles in comparison to patients without these alleles. The data in this study suggest that human leucocyte antigen-DR locus, or other genes in linkage disequilibrium, may play an important role in asthma phenotype expression in patients with grass-pollen allergy as well as in determining total immunoglobulin E levels in these patients.

Adolescent↗

A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force.

This report has been prepared by an EAACI task force representing the five EAACI Sections and the EAACI Executive Committee composed of specialists that reflect the broad opinion on allergy expressed by various clinical and basic specialties dealing with allergy. The aim of this report is to propose a revised nomenclature for allergic and related reactions that can be used independently of target organ or patient age group. The nomenclature is based on the present knowledge of the mechanisms which initiate and mediate allergic reactions. However, the intention has not been to revise the nomenclature of nonallergic hypersensitivity.

Humans↗

Pre-operative levels of serum immunoglobulins, circulating immune complexes and complement proteins in patients with different types of neoplasms.

In the sera of 30 neoplasm patients without metastases, the average IgG level was higher than in the control group (CG) (18.16+/-5.10 vs. 12.62+/-2.14 g/l or 12.22+/-2.14 after excluding an outier). Average concentrations of circulating immune complexes (CIC), IgM, complement 1 inhibitor (Cli), C3c and C4 did not statistically differ between the groups. Dividing the patients' group into: breast or ovary cancer (BC), melanoma (M), digestive tract cancer (DT) and other neoplasms (ON) subgroups revealed that the IgG increase did not apply to the BC group. Relatively decreased CIC concentrations in the BC and DT group and an increased Cli in the DT group were found. Several diversities detected in the humoral immunity indices' distributions and correlations suggest activation of different mechanisms depending on the neoplasm types.

Adult↗

Serum TNF-alpha level in the neoplasm patients qualified for surgical treatment.

The aim of the study was to analyze serum tumor necrosis factor alpha (TNF-alpha) levels in patients with different neoplasm types qualified for surgical treatment and to evaluate their possible correlations with circulating immune complexes (CIC), IgG, IgM, and the complement (C) compounds: C1 inhibitor (C1i), C3c and C4 levels. Studies were performed in sera from 30 neoplasm patients before surgical treatment and in 10 persons from a control group (CG) with no malignancy. Serum TNF-alpha levels were measured with the Cytogen ELISA kit. Average TNF-alpha levels measured in neoplastic patient groups qualified for surgical treatment were not significantly different from the average TNF-alpha level in the CG group.

Complement System Proteins↗

[The role of cyclooxygenase and prostaglandins in the pathogenesis of rheumatoid arthritis].

Rheumatoid arthritis (RA) is a systemic inflammatory disease with polyarticular synovitis leading to formation of rheumatoid pannus and subsequent erosion of articular cartilage and bone. Prostaglandins (PGs)--a group of arachidonic acid metabolites found at elevated levels in synovial fluid and synovial membrane are considered to play a pivotal role in development of vasodilatation, fluid extravasation and pain in synovial tissues. Moreover, there is increasing evidence that PGs (especially prostaglandin E2) are mediators involved in complex interactions leading to development of erosions of articular cartilage and juxta-articular bone. Cyclooxygenase is an enzyme playing crucial role in PGs production. It is known that two forms of cyclooxygenase exist: cyclooxygenase-1 (COX-1) playing house-keeping functions and cyclooxygenase-2 (COX-2) involved in inflammatory responses. Synovial tissues from patients with RA are shown to contain COX-2 and to a less extent COX-1. COX-2 expression in rheumatoid synovium is induced by proinflammatory cytokines, mainly IL-1, while corticosteroids are capable of inhibiting COX-2 expression. The understanding of crucial role of COX-2 in synovial inflammation led to development of new group of anti-inflammatory agents--selective COX-2 inhibitors, that inhibit specifically COX-2, providing effective anti-inflammatory action without the side effects associated with inhibition of COX-1. In the context of widespread use of selective COX-2 inhibitors hypothetical role of COX-1 in RA pathology should be elucidated.

Anti-Inflammatory Agents, Non-Steroidal↗

Search for new synthetic immunosuppressants II. Tetrazole analogues of hymenistatin I.

Linear and cyclic hymenistatin I (HS I) analogues with dipeptide segments Ile2-Pro3 Pro3-Pro4 and Val6-Pro7 replaced by their tetrazole analogues Ile2-psi[CN4]-Ala3', Pro3-psi[CN4]-Ala4 and Val6-psi[CN4]-Ala7 were synthesized by the solid phase peptide synthesis method and cyclized with the TBTU and/or HATU reagent. The peptides were examined for their immunosuppressive activity in the lymphocyte proliferation test (LPT).

Amino Acid Sequence↗