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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

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↗

The release of eosinophil chemotactic activity and eosinophil chemokinesis inhibitory activity by mononuclear cells from atopic asthmatic and non-atopic subjects.

The goal of our study was to assess the chemotactic activity for eosinophils (ECA) and neutrophils (NCA) and histamine releasing activity (HRA) in crude supernatants of mononuclear cells in monosensitized atopic asthmatics and healthy controls. Chemotactic activity for ECA and neutrophils was measured in supernatants of cultured mononuclear cells with modified Boyden's chamber and HRA was assessed on healthy donor basophils. With respect to ECA generation two distinct subgroups of subjects were distinguished: releasers [ECA (+)] and non-releasers [ECA (-)]. In atopic and non-atopic ECA (+) the mean ECA index was 3.78 +/- 0.49 and 2.47 +/- 0.27 respectively (P > 0.05). Supernatants from the remaining subjects (seven of 22 atopic and five of 11 non-atopic) did not express ECA, but revealed significant inhibitory activity for chemokinesis of eosinophils (mean chemotactic index 0.25 +/- 0.16 and 0.48 +/- 0.22 for atopic and non-atopic non-releasers respectively). Stimulation with antigen of MNC from atopic and with PHA from non-atopic ECA (-) restored cells ability to release ECA. Sephadex gel chromatography revealed that supernatants of MNC contained chemotactic and chemokinesis inhibitory activity in different fractions. The spontaneous productions of NCA and HRA by mononuclear cells was similar in ECA releasers and non-releasers, although the HRA was higher following stimulation with PHA in the non-atopic ECA (+) subgroup. Our study demonstrated, for the first time, that MNC are capable of generating not only chemotactic activity but also chemokinesis inhibitory activity for eosinophils.

Adult↗

Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients.

The mechanism of aspirin (acetylsalicylic acid [ASA]) sensitivity associated with severe asthma and chronic rhinosinusitis with nasal polyps ("aspirin triad") has been attributed to arachidonic metabolism alternations, although the putative biochemical defects have not been elucidated. The aim of this study was assessment of the hypothesis that local production of eicosanoids in the respiratory epithelium in patients with ASA-sensitive asthma/rhinosinusitis (ASARS) differs from that of ASA-tolerant patients with rhinosinusitis (ATRS). Nasal polyps were obtained from 10 patients with ASARS and 15 with ATRS during routine polypectomies, and epithelial cells (ECs) were cultured on bovine collagen type I matrix (Vitrogen 100), in medium supplemented with growth factors. The generation of eicosanoids in supernatants of confluent ECs (6 to 8 d of culture; purity > 98%) was quantified by immunoassays. Unstimulated ECs from ASARS patients generated significantly less prostaglandin E(2)(PGE(2)) compared with ATRS (0.8 +/- 0.3 versus 2. 4 +/- 0.5 ng/microg double-stranded deoxyribonucleic acid [dsDNA], respectively), although a similar relative increase in response to calcium ionophore and inhibition with ASA was observed in both groups. Basal levels of 15-hydroxyeicosatetraenoic acid (15-HETE) were not different between groups, and calcium ionophore enhanced its production to a similar extent. However, cells incubation with 200 microM ASA for 60 min resulted in a significant increase (mean +359%) in 15-HETE generation only in ASARS patients, whereas no effect of ASA on 15-HETE generation in ATRS patients was observed. PGF(2alpha) generation was similar in both groups, and no significant generation of PGD(2) or leukotriene C(4) (LTC(4)) was observed in epithelial cell cultures from either group. Our results indicate that nasal polyps ECs from ASA-sensitive patients have significant abnormality in basal and ASA-induced generation of eicosanoids which may be causally related to the mechanism of ASA sensitivity.

Adult↗

[Point scale quantification of changes in computed tomography of chronic hyperplastic rhinosinusitis].

Coronal CT scans have dramatically improved imaging of the nasal cavity and paranasal sinuses. However, quantification of the extent of chronic sinusitis is not possible by simple reviewing of the CT images. The aim of the study was to introduce a CT scoring scale to assess the extend of sinusal pathology. Seventeen patients with clinically recognized aspirin-sensitive rhinosinusitis asthma syndrome (aspirin triad) were studied. The CT scans were reviewed and scored for extent of the disease by two independent radiologists. Repeated readings of the scans showed close correlation between the two assessments. The authors conclude, that CT scoring system for quantitation of the disease extent is reproducible and may be useful in clinical practice.

Adult↗

Nasal reactivity to capsaicin in patients with seasonal allergic rhinitis during and after the pollen season.

BACKGROUND: We aimed to study the participation of neurogenic mechanisms in nasal allergic inflammation by assessing the effect of neurogenic stimulation on the secretory and cellular responses of nasal mucosa in patients with allergic rhinitis. METHODS: A group of patients suffering from seasonal allergic rhinitis was challenged intranasally with incremental doses of capsaicin (0.3, 3, 12 microg) during and after the pollen season. Clinical symptoms after provocations were monitored, and unilateral nasal lavages were obtained. The nasal lavage fluid (NAL) was assayed for concentration of total protein, albumin, lactoferrin, and number of leukocytes, following by differential count. RESULTS: Capsaicin challenge during the pollen season produced greater congestion (P < 0.01) and rhinorrhea (P < 0.05) than after the season. The intensity of burning sensation (pain) was similar on both occasions. Capsaicin failed to increase albumin content in NAL both during and after the season. Total protein was increased only after the highest dose of capsaicin (P < 0.03) after the season. The number of eosinophils in basal lavages was higher during the season. During the season, the total number of leukocytes at least doubled in 7/12 patients and the percentage of eosinophils increased in 6/12 patients after the capsaicin challenge. CONCLUSIONS: Our study demonstrated that during the symptomatic period the nasal mucosa of allergic patients is more susceptible to neurogenic stimulation, showing enhanced secretory and inflammatory (cellular) responses.

Airway Resistance↗

Association of pyrazolone drug hypersensitivity with HLA-DQ and DR antigens.

BACKGROUND: In sensitive patients pyrazolone drugs can precipitate adverse reactions ranging from urticaria and angioedema to anaphylactic shock, presumably by immunological, IgE-mediated mechanism. However, up to now no genetic factors influencing the development of allergic reaction have been reported in this type of hypersensitivity. OBJECTIVE: The aim of our study was the investigation whether the susceptibility to development of pyrazolone drugs hypersensitivity (PDH) reactions was associated with HLA class II antigens. METHODS: To test this hypothesis we studied the distribution of HLA-DR and DQ antigens in 26 pyrazolone sensitive patients and control groups including unselected general population and clearly defined atopic and non-atopic groups. RESULTS: Significantly higher frequencies of DQ 7 and DR11 antigens were found in PDH group as compared with control unselected population (RR= 16.48, P < 0.0001; P(cor)< 0.002 and RR = 4.57, P = 0.0002; Pcor = 0.003 for DQ and DR antigen respectively). Similarly, statistically significant increased frequencies of DQ 7 and DR11 in patients with PDH were observed compared with atopic control group (RR= 18.43, P < 0.0001; Pcor <0.002 and RR= 6.33, P= 0.0007; Pcor =0.01, for DQ and DR antigen respectively). However, in comparison to non-atopic control group only the frequency of DQ 7 antigen was significantly increased (RR = 15.42, P = 0.0001; Pcor = 0.0015). DQ 7 antigen was present in 46.1% of PDH patients compared with 4.9%, 4.4% and 5.3% in the general population, atopic and non-atopic groups respectively, suggesting pyrazolone hypersensitivity as a trait positively correlated with this HLA antigen. CONCLUSION: Our data suggest a genetic predisposition to pyrazolone hypersensitivity reactions, linked to HLA-DQ locus.

Adolescent↗

Culture of human nasal epithelial cells from nasal polyps on collagen matrix.

Epithelial cell cultures became an experimental model employed for both animal and human studies. We established a modified method of culture of human nasal epithelial cells from nasal polyps using serum-free, hormonally supplemented Ham's F-12 medium and Vitrogen 100 collagen matrix. Cells reached confluent monolayer structures in 5 to 7 days (mean time 6 +/- 0.89 days) of culture. The confluent cultures consisted of pure epithelial cells, which was confirmed by light and electron microscopy, and immunohistochemical staining with anticytokeratin antibody. The success ratio of cultures was 61.5%. The culture system described is efficient enough to provide pure epithelial cells for further functional studies.

Cell Culture Techniques↗