| 1. |
- Bergman, Vivi, et al.
(författare)
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Urinary excretion of 8-hydroxydeoxyguanosine and malondialdehyde after high dose radiochemotherapy preceding stem cell transplantation
- 2004
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 36:3, s. 300-306
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Tidskriftsartikel (refereegranskat)abstract
- The urinary excretion of the hydroxylated DNA base 8-hydroxydeoxyguanosine (8-OHdG) and the lipid peroxidation product malondialdehyde (MDA) was monitored in 11 patients with hematological malignancies undergoing total body irradiation and high-dose chemotherapy preceding bone marrow transplantation. Nine patients showed a prompt increase in urinary 8-OHdG (8-25 times the initial baseline level) on days 0-7 after irradiation onset, the excretion then decreased during the aplastic period and increased again when engraftment took place (in 7 patients). A significant positive correlation was found between urinary 8-OHdG and whole blood leukocyte count, both on day 5 (p = .04, r = .72) and on day 22 (p = .009, r = .80) after irradiation onset. One patient who lacked the first peak of 8-OHdG excretion showed low blood leukocyte counts (less than 2×109/l) before therapy onset, this patient, however, later had a successful engraftment and then also showed considerable increases in both 8-OHdG excretion and leukocyte count. These observations suggest leukocytes play a part in the excretion of 8-OHdG after conditioning therapy preceding bone marrow transplantation. As opposed to the biphasic 8-OHdG excretion, the excretion of MDA showed a single peak appearing on days 11-19 after radiochemotherapy onset, i.e., during the period in which the patients suffered from cytopenia, mucositis, and other side effects of the treatment. It is suggested, therefore, that these clinical manifestations are associated with increased lipid peroxidation. Altogether, these findings illustrate the utility of serial urinary samples for monitoring oxidative stress due to conditioning therapy in clinical practice. They also demonstrate that different oxidative stress markers may behave quite differently regarding their appearance in the urine after whole-body oxidative stress.
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| 2. |
- Ghafouri, Bijar, 1972-, et al.
(författare)
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PLUNC in human nasal lavage fluid : multiple isoforms that bind to lipopolysaccharide
- 2004
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Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - 1570-9639 .- 1878-1454. ; 1699:1-2, s. 57-63
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Tidskriftsartikel (refereegranskat)abstract
- Here, we demonstrate the presence of multiple isoforms of palate lung nasal epithelial clone (PLUNC) in human nasal lavage fluid (NLF). Eight isoforms were separated by two-dimensional gel electrophoresis (2-DE), and peptide mapping of the proteins was performed using MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry) of tryptic and asparginase cleavages. The identification was verified by amino acid sequencing after analysis of collision-induced dissociation (CID) fragmentation spectra with nanoelectrospray MS/MS. One isoform showed an electrophoretic mobility shift after N-glycosidase treatment, indicating that at least one of the PLUNC isoforms is glycosylated. We also demonstrate that PLUNC in NLF binds to lipopolysaccharide (LPS) in vitro; indeed, out of all proteins present in NLF only the PLUNC isoforms were found to adsorb to an LPS-coated surface. These results show that PLUNC is expressed as multiple LPS-binding isoforms in human NLF. The possibility that PLUNC may play a role in the innate immune response of the upper airways is inferred.
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| 3. |
- Ghafouri, Bijar, 1972-, et al.
(författare)
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PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid
- 2003
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 31:4, s. 810-814
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Tidskriftsartikel (refereegranskat)abstract
- PLUNC (palate, lung and nasal epithelial clone) is a newly discovered gene that is expressed in the upper respiratory tract and is suggested to be of importance in host defence against bacteria. We have identified two forms of the PLUNC protein in human nasal lavage fluid (NLF) using two-dimensional gel electrophoresis (2-DE) and MS. The apparent molecular masses and isoelectric points of these forms are 24.8 kDa/pI 5.4 and 25.1 kDa/pI 5.5. Notably, the 24.8 kDa/pI 5.4 form of PLUNC is an abundant protein in the 2-DE protein patterns of NLF from healthy subjects. Decreased levels of PLUNC were found in NLF from smokers and workers exposed to reactive epoxy chemicals, indicating that long-term exposure to airway irritants impairs the production of PLUNC in the upper respiratory tract. We have also investigated the presence of lipopolysaccharide (LPS)-binding proteins in NLF. Five proteins were found to adsorb to a LPS-coated surface; two of these proteins correspond to the two PLUNC forms, as judged by 2-DE pattern matching. For comparison, human saliva was found to contain a set of LPS-binding proteins with similar 2-DE spot positions (the same pIs but somewhat lower apparent molecular masses of 20 kDa). These results indicate that PLUNC may be a new marker of airway inflammation and may play a part in the innate immune response, and that human saliva contains yet other members of the family of LPS-binding proteins.
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| 4. |
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| 5. |
- Carstensen, U, et al.
(författare)
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Influence of genetic polymorphisms of biotransformation enzymes on gene mutations, strand breaks of deoxyribonucleic acid, and micronuclei in mononuclear blood cells and urinary 8-hydroxydeoxyguanosine in potroom workers exposed to polyaromatic hydrocarbons
- 1999
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 25:4, s. 351-360
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Airborne exposure to polycyclic aromatic hydrocarbons (PAH) in the potroom of an aluminum reduction plant was studied in relation to genotoxic or mutagenic effects, and the possibility of host genotypes of different metabolizing enzymes modifying associations between PAH exposure and genotoxic or mutagenic response was assessed. SUBJECTS AND METHODS: Ninety-eight male potroom workers and 55 male unexposed blue-collar workers constituted the study population. Micronuclei in CD4+ and CD8+ lymphocytes, DNA (deoxyribonucleic acid) single-strand breaks, hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation frequency, and genotype for cytochrome P-4501A1, glutathione transferases M1, T1 and P1, and microsomal epoxide hydrolase were analyzed using peripheral mononuclear cells. Urine samples were collected for the analysis of 8-hydroxydeoxyguanosine. RESULTS: Micronuclei in peripheral CD4+ and CD8+ lymphocytes, DNA single-strand breaks, HPRT mutation frequency, and 8-hydroxydeoxyguanosine in urine did not differ between the potroom workers and the unexposed referents. With the exception of an observed exposure-response relationship for potroom workers with Tyr/Tyr genotype for microsomal epoxide hydrolase, between airborne PAH and CD8+ micronuclei, no correlations were found between any of the genotoxicity biomarkers and any of the exposure measures (airborne particulate PAH, airborne gas phase PAH, length of employment in the potroom, 1-hydroxypyrene in urine, or PAH-DNA adducts in peripheral lymphocytes), also when genotypes for biotransforamtion enzymes were considered. CONCLUSIONS: The results indicate that the employed biomarkers of mutagenic or genotoxic effects are not appropriate for surveillance studies of potroom workers exposed to current airborne levels of PAH. The significance of the correlation between airborne PAH and CD8+ micronuclei in Tyr/Tyr genotype subjects should be evaluated.
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| 6. |
- Ghafouri, Bijar, 1972-, et al.
(författare)
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Comparative proteomics of nasal fluid in seasonal allergic rhinitis
- 2006
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 5:2, s. 330-338
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Tidskriftsartikel (refereegranskat)abstract
- A comparative proteomic approach was applied to examine nasal lavage fluid (NLF) from patients with seasonal allergic rhinitis (SAR, n = 6) and healthy subjects (controls, n = 5). NLF samples were taken both before allergy (pollen) season and during season, and proteins were analyzed by two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) after tryptic cleavage. Twenty proteins were selected and quantified. During allergy season, the levels of six sialylated isoforms of PLUNC (palate lung nasal epithelial clone) were lower in SAR patients than controls, as were the levels of six isoforms of von Ebner's gland protein (VEGP), including a previously undescribed form with N-linked glycosylation, and of cystatin S. PLUNC is a new innate immunity protein and VEGP and cystatin S are two endogenous proteinase inhibitors. By contrast, the levels of an acidic form of alpha-1-antitrypsin were higher in SAR patients than controls. One previously unidentified NLF protein was found in all samples from the SAR patients during allergy season but not in any sample before allergy season: this protein was identified as eosinophil lysophospholipase (Charcot-Leyden crystal protein/galactin 10). MS/MS analysis of the N-terminus of the protein showed removal of Met and acetylation of Ser. Altogether, these findings illustrate the potential use of proteomics for identifying protein changes associated with allergic rhinitis and for revealing post-translational modifications of such new potential markers of allergic inflammation.
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| 7. |
- Ghafouri, Bijar, 1972-, et al.
(författare)
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Mapping of proteins in human saliva using two-dimensional gel electrophoresis and peptide mass fingerprinting
- 2003
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 3:6, s. 1003-1015
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Tidskriftsartikel (refereegranskat)abstract
- Human saliva contains a large number of proteins that can be used for diagnosis and are of great potential in clinical and epidemiological research. The aim of this work was to map the proteins in saliva by two-dimensional gel electrophoresis (2-DE), and to identify abundant proteins by peptide mass fingerprinting using trypsin cleavage and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry analysis. One hundred proteins were identified representing 20 different identities according to accession numbers. Abundant proteins expressed in different forms were: α-amylase, immunoglobulin A, prolactin-inducible protein, zinc-α2-glycoprotein and cystatins (S, SA, D and SN). Other proteins found were interleukin-1 receptor antagonist, von Ebner’s gland protein (lipocalin-1) and calgranulin A and B (S100A8 and A9). Furthermore, apolipoprotein A-I, β2-microglobulin, glutathione S-transferase P and fatty acid-binding protein were also identified. Our results show that human saliva contains a large number of proteins that are involved in inflammatory and immune responses. The 2-DE protein map constructed opens the possibility to investigate protein changes associated with disease processes.
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| 8. |
- Ghafouri, Bijar, et al.
(författare)
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Newly identified proteins in human nasal lavage fluid from non-smokers and smokers using two-dimensional gel electrophoresis and peptide mass fingerprinting
- 2002
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Ingår i: Proteomics. - 1615-9853 .- 1615-9861. ; 2:1, s. 112-120
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Tidskriftsartikel (refereegranskat)abstract
- Human nasal lavage fluids (NLFs) were analyzed with two-dimensional gel electrophoresis (2-DE) and proteins were identified with peptide mass fingerprinting using matrix-assisted laser desoption/ionization time of flight mass spectrometry. In some cases, the identification was verified by analysis of post-source decay fragmentation spectra. Many of the identified proteins were new forms or fragments of previously found proteins (e.g. albumin, lactoferrin, cystatin, calgranulin, von Ebners gland protein and palate lung nasal epithelium clone), while others were proteins that have previously been indicated by 2-DE image matching or immunoblots (e.g. apolipoprotein AI, lysozyme C, and Clara cell secretory protein). Some new proteins, not shown before in 2-DE patterns of NLF were also found, e.g. mammaglobin B, 2-microglobulin and immunoglobulin J chain. Of the identified NLF proteins many appear to be involved in inflammatory and immune responses. A study was therefore conducted to investigate if the levels of these proteins were changed in smokers compared to nonsmokers. It was found that NLF from smokers contained decreased levels of Clara cell secretory protein, and increased proportions of a truncated variant of lipocortin-1, three acidic forms of α1-antitrypsin, and one phosphorylated form of cystatin S. Furthermore, NLF from smokers contained increased proportions of a new variant of palate lung nasal epithelium clone (PLUNC), a recently identified airway irritation marker. The results demonstrate that 2-DE of NLF may be used to assess alterations of proteins or post-translationally modified proteins in smokers. Clara cell secretory protein (CC 16, CC 10) and lipocortin-1 are two anti-inflammatory, phospholipase A2 inhibitory proteins, and α1-antitrypsin and cystatin S are two proteinase inhibitors. Changed levels of these proteins may therefore be of importance to the airway inflammation caused by smoking. The results also support the notion that PLUNC is involved in inflammatory responses in the upper airways.
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| 9. |
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| 10. |
- Hammar, Mats, 1950-, et al.
(författare)
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Strålning, cancer och forskarutbildning
- 2007
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 104
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 11. |
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| 12. |
- Kristenson, Margareta, 1950-, et al.
(författare)
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Lower serum levels of beta-carotene in Lithuanian men are accompanied by higher urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine : The LiVicordia study.
- 2003
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Ingår i: Nutrition (Burbank, Los Angeles County, Calif.). - 0899-9007 .- 1873-1244. ; 19:1, s. 11-15
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In 1995, middle-aged Lithuanian men had a four-fold higher risk than Swedish men of dying from coronary heart disease. The cross-sectional LiVicordia study had reported significantly lower levels of the lipid-soluble antioxidants lycopene, ▀-carotene, and ?-tocopherol among Lithuanian men than among Swedish men. We examined whether there were differences in urinary 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative stress, between these groups of men. METHODS: Using automated coupled column high-performance liquid chromatography with electrochemical detection, we examined 50-y-old men randomly sampled from Link÷ping, Sweden (n = 99) and Vilnius, Lithuania (n = 109) with regard to urinary concentrations of 8-OHdG. RESULTS: Levels of 8-OHdG were higher in the Lithuanian men than in the Swedish men (20.9 ▒ 0.91 versus 14.9 ▒ 0.75 nM/L, P < 0.001), and this difference was evident in smokers (P < 0.01) and non-smokers (P < 0.001). Serum levels of a- and ▀-carotene were inversely correlated to urinary 8-OHdG levels (P < 0.05 in both cases). Habitual smoking and low levels of ▀-carotene contributed significantly to higher oxidative DNA damage expressed as urinary 8-OHdG. CONCLUSIONS: These findings indicate that increased urinary 8-OHdG levels accompany lower serum levels of antioxidants in Lithuanian men. They supported previous suggestions that increased oxidative stress may be one factor behind the higher mortality in Lithuanian men. ⌐ Elsevier Science Inc. 2003.
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| 13. |
- Kristjansson, I, et al.
(författare)
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Assessment of aluminium in human deciduous teeth
- 2000
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Ingår i: European Journal of Epidemiology. - 0393-2990 .- 1573-7284. ; 16:3, s. 231-233
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Tidskriftsartikel (refereegranskat)abstract
- The possible role of environmental aluminium exposure in the pathogenesis of various diseases has highlighted the need for methods by which the long-term exposure to aluminium can be assessed. Therefore, we have further developed a method to determine aluminium in human deciduous teeth and applied this method for studying populations in Sweden, Crete and Iceland.
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| 14. |
- Lindahl, Mats, 1957-, et al.
(författare)
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Demonstration of different forms of the anti-inflammatory proteins lipocortin-1 and Clara cell protein-16 in human nasal and bronchoalveolar lavage fluids
- 1999
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Ingår i: Electrophoresis. - 0173-0835 .- 1522-2683. ; 20:4-5, s. 881-890
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Tidskriftsartikel (refereegranskat)abstract
- The anti-inflammatory proteins lipocortin-1 and Clara cell protein-16 (CC-16) were studied in two-dimensional gel electrophoresis (2-DE) protein patterns of human nasal lavage fluids (NLFs) and bronchoalveolar lavage fluids (BALFs). Seven forms of lipocortin-1 were detected with Western immunoblots: three isoforms with an apparently normal Mr of 38 kDa and pI of 5.9, 6.0 and 6.1, and four truncated variants with pI/kDa 6.0/36, 6.4/36, 7.0/33, and 7.4/34. Four 6 kDa isoforms of CC-16 were found with pI 4.6, 4.8, 4.9, and 5.2. Lipocortin-1 and CC-16 were expressed in all individuals tested although not all variants were found in each individual. The overall levels of lipocortin-1 were higher in BALF than NLF and there were significant differences in the distribution of the different lipocortin-1 forms between BALFs and NLFs. One patient with occupational asthma and four children with rhinitis had increased levels of one of the truncated lipocortin-1 forms in NLF (pI/kDa: 7.4/34) and decreased levels of the major CC-16 form (pI/kDa: 4.8/6). The levels of CC-16 but not of lipocortin-1 were higher in BALF from smokers than from nonsmokers. These results indicate that the levels of lipocortin-1 and CC-16 in NLF and BALF may be altered in inflammatory airway disorders. Furthermore, the identification of different forms of the two proteins makes possible more detailed studies on the role of these proteins in inflammatory disease processes and anti-inflammatory therapies.
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| 15. |
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| 16. |
- Lindahl, Mats, 1957-, et al.
(författare)
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Nasal lavage fluid and proteomics as means to identify the effects of the irritating epoxy chemical dimethylbenzylamine
- 2004
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Ingår i: Biomarkers. - : Informa UK Limited. - 1354-750X .- 1366-5804. ; 9:1, s. 56-70
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to describe the changes in the nasal lavage fluid (NLF) protein pattern after exposure to the irritating epoxy chemical dimethylbenzylamine (DMBA) and to identify the affected proteins using a proteomic approach. The protein patterns of NLF from six healthy subjects and eight epoxy workers with airway irritation were analysed using two-dimensional gel electrophoresis (2-DE) before and after exposure to 100 μg m-3 DMBA for 2 h in an exposure chamber. NLF proteins were identified by (i) comparison with a 2-DE NLF reference database, (ii) N-terminal amino acid sequencing, and (iii) mass spectrometry. In NLF from healthy subjects, the levels of immunoglobulin A increased and the levels of Clara cell protein 16 (CC16) decreased after chamber exposure, while in NLF from epoxy workers, α2-macroglobulin and caeruloplasmin increased. Two previously unidentified proteins decreased in NLF from epoxy workers after exposure, these were identified as statherin and calgranulin B. In addition, the subjects who developed high counts of eosinophils in their nasal mucosa after chamber exposure had significantly lower levels of immunoglobulin-binding factor (IgBF) before exposure than subjects with low eosinophil infiltration. These results show that short-term exposure to DMBA causes distinct changes in NLF proteins. Moreover, three proteins that have previously not been associated with upper airway irritation were identified: statherin, calgranulin B and IgBF. Further studies are needed to investigate whether these proteins may be used as biomarkers of airway irritation and to give new insight into the ways in which occupational exposure to irritants causes inflammation of the airways.
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| 17. |
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| 18. |
- Lindbom, John, 1960-, et al.
(författare)
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Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa
- 2001
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 18:1, s. 130-138
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Tidskriftsartikel (refereegranskat)abstract
- Phospholipase A2 (PLA2) is a family of enzymes thought to play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor. However, the precise contribution of different PLA2 types to the formation of inflammatory lipid mediators in the upper airways is not known and the expression of different PLA2 genes in the human nasal mucosa has not been examined.This study therefore investigated the occurrence of messenger ribonucleic acids (mRNAs) for different PLA2 forms (IB, IIA, IID, IIE, III, IVA, IVB, IVC, V, VI, VII, X, acid calcium-independent (aiPLA2), and calcium-independent membrane bound PLA2, (iPLA2-2)) in the nasal mucosa of five healthy human subjects.Using reversed transcription-polymerase chain reaction (RT-PCR) techniques it was found that all these PLA2 types except PLA2 V were expressed in all subjects, whereas PLA2 V was detected in only one individual on one single occasion. The relative abundance of the different PLA2 transcripts were aiPLA2>X≈IVA>IIA≈IIE≈IVB≈VI>IB≈IID≈III≈IVC≈VII≈iPLA2-2. To further quantify the mRNA-expression of PLA2 X, IVA and IIA, the samples were reanalysed with a quantitative PCR-technique utilizing competitive deoxyribonucleic acid (DNA) mimics as references. The amounts of PLA2 X, IVA and IIA mRNA were then estimated to 0.9±0.2, 1.1±0.7, and 0.0025±0.0021 amol (mean±se), respectively, confirming the relative abundance of these PLA2 transcripts and indicating that the recently described PLA2 X form is relatively strongly expressed.These findings demonstrate that a large number of PLA2 types are expressed in the normal human nasal mucosa. Moreover, this investigation demonstrates, for the first time, the presence of the newly discovered phospholipase A2 forms IID, IIE, III, IVB, IVC, X and calcium-independent membrane bound phospholipase A2 in the human nasal mucosa and raises the possibility that one or several of these may be involved in inflammatory reactions in the nose.
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| 19. |
- Lindbom, John, 1960-, et al.
(författare)
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Increased gene expression of novel cytosolic and secretory phospholipase A2 types in human airway epithelial cells induced by tumor necrosis factor-α and IFN-γ
- 2002
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Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 22:9, s. 947-955
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Tidskriftsartikel (refereegranskat)abstract
- Phospholipase A2 (PLA2) is a growing family of enzymes that may play a major role in inflammation. We investigated the effect of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types (IB, IIA, IID, IIE, IIF, III, IVA, IVB, IVC, V, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII, and XIII) in human bronchoepithelial (BEAS-2B) and nasal epithelial (RPMI 2650) cells. The cells were stimulated with TNF-α or IFN-γ for different lengths of time (1, 4, 18, and 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase-PCR (RT-PCR) and normalized to those of the housekeeping gene, GAPDH. In both cell lines, TNF-α increased the expression of PLA2 IVA and IVC, and IFN-γ increased the expression of PLA2 IIA and IID. No influence on the gene expression of PLA2-activating protein (PLAP) was noted on cytokine stimulation. These findings indicate that TNF-α and IFN-γ induce gene expression of two novel cytosolic and secretory PLA2 types (IVC and IID, respectively) in human airway epithelial cells. The possibility that these PLA2 types are involved in cytokine-mediated inflammation in the respiratory tract is inferred.
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| 20. |
- Lindbom, John, 1960-, et al.
(författare)
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Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis
- 2004
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Ingår i: Rhinology. - 0300-0729 .- 1996-8604. ; 42:2, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Phospholipase A2 (PLA2) is a family of enzymes that play different role(s) in inflammation, but their importance in seasonal allergic rhinitis (SAR) has not been clarified. Here, we determined the levels of messenger ribonucleic acid (mRNA) for different PLA2 types in the nasal mucosa of SAR patients (n=6) and healthy controls (n=5). Nasal brush samples were taken both during pollen season, when the symptoms of the patients were severe, and off-season, when the patients were free of symptoms. We found that PLA2 IB, IIA, IID,IIE, IIF III, IVA, IVB, IVC, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII and XIII were all expressed in each subject at both occasions. The mRNA levels of PLA2 VIIA (platelet-activating factor (PAF) acetylhydrolase) were lower in SAR patients than controls, both during pollen season (p = 0.03) and off season (p = 0.03). These findings demonstrate that a large number of PLA2 types are expressed in the nasal mucosa, regardless of whether there is ongoing allergic inflammation or not. The observation that PAF acetylhydrolase mRNA expression in the nasal mucosa is lower in SAR patients than in healthy subjects suggests the possibility that impaired ability to inactivate PAF might be of importance in SAR. Further studies are required to clarify whether the decreased PAF acetylhydrolase mRNA expression in SAR is accompanied by decreased enzyme activity and whether aberrations in PAF acetylhydrolase are present in infectious rhinitis patients as well.
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| 21. |
- Nosratabadi, Ali Reza, 1964-, et al.
(författare)
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Clara cell 10-KDA protein inhibits endotoxin-induced airway contraction in isolated perfused rat lungs
- 2003
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Ingår i: Experimental Lung Research. - : Informa UK Limited. - 0190-2148 .- 1521-0499. ; 29:7, s. 455-473
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Tidskriftsartikel (refereegranskat)abstract
- Clara cell 10-kDa protein (CC10) is a major component of bronchoalveolar lavage fluid and is suggested to be a natural regulator of airway inflammation, possibly through its effects on theproin-flammatory enzyme(s), phospholipase A2. We examined the effect of recombinant human (rh) CC10 on endotoxin-induced airway contraction and cytokine release in isolated perfused rat lungs. We found that rhCC10 added to the lung perfusate abolished the endotoxin-induced airway contraction, and that it inhibited both the release of interleukin-1▀ and interleukin-6 into the lung perfusate and the release of tumor necrosis factors, into the pulmonary lavage fluid. By contrast, the levels of interferon-? were unaffected by CC10 administration. Rutin, a phospholipase A2 inhibitor, and N?-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, also attenuated the contraction induced by endotoxin. These findings demonstrate that rhCC10 inhibits endotoxin-induced airway contraction and the release of proinflammatory cytokines (interleukin-1▀, interleukin-6, and tumor necrosis factor-a) in isolated perfused rat lungs. The results also indicate that phospholipase A2 and nitric oxide are involved in the airway contraction in this model, possibly through their influence on the production of eicosanoids.
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| 22. |
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| 23. |
- Söderholm, Johan D, 1958-, et al.
(författare)
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Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of crohn's disease
- 2002
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 50:3, s. 307-313
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Tidskriftsartikel (refereegranskat)abstract
- Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=l 2) were studied, and ileal specimens from colon cancer patients (n=l 3) served as controls. Methods: Mucosal permeability to 51Cr-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Results: Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability - that is, increased permeation of 51Cr-EDTA and decreased electrical resistance - which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. Conclusions: The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease.
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