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Biomedical subjects

C Svensson

Publications and source records attributed to C Svensson.

At least 163 records · Page 9Linked to original sources

Plasma exudation as a first line respiratory mucosal defence.

A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin, complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudate would have important roles in normal airway defence. Recent observations in guinea-pig tracheobronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an 'unfiltered' plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.

Absorption↗

Eosinophils, secretory responsiveness and glucocorticoid-induced effects on the nasal mucosa during a weak pollen season.

This study examined the seasonal effects on eosinophils and secretory responsiveness of the nasal mucosa in 22 patients with allergic rhinitis due to birch pollen (11 patients received placebo and 11 budesonide, 200 micrograms once daily in each nostril). The pollen counts during the study season were too low to produce a significant symptomatology. Hence, our findings demonstrate threshold alterations of the airway mucosa in allergic rhinitis and their inhibition by anti-inflammatory drug intervention. The patients were monitored for 8 weeks with daily recordings of pollen counts and symptom scores. Once every week a series of laboratory tests was carried out: the local eosinophil influx was determined using a Rhinobrush technique; the levels of eosinophil cationic protein (ECP) were analysed in nasal lavage fluids; and the secretory response to intranasal methacholine was measured. Treatments started after a 2-week run-in period. The proportion of eosinophils increased markedly in the placebo group and was elevated also during the last two study weeks when the pollen counts were practically nil. The secretory responsiveness to methacholine increased during the pollen season and returned to baseline towards the end of the study period. The topical glucocorticoid treatment reduced the proportion of eosinophils, the ECP levels, and the secretory response to methacholine compared to placebo. We conclude that the increased traffic and activity of eosinophils and less conspicuously the increased secretory responsiveness are expressions of the mucosal inflammation that precede the development of symptoms in seasonal allergic rhinitis.

Administration, Intranasal↗

Exhibition of specific alterations in activities and mRNA levels of rat islet glycolytic and mitochondrial enzymes in three different in vitro model systems for attenuated insulin release.

We studied the possible relationships between the functional status of the beta-cell and activities or mRNA contents of enzymes involved in the catabolism of glucose. Three different in vitro models with attenuated insulin response were used: rat islets cultured at a low glucose concentration, rat islets incubated in vitro with streptozocin, and fetal rat islets. The fetal and streptozocin-administered islets were compared with adult islets cultured in RPMI-1640 containing 11 mM glucose, and the effects of the in vitro glucose concentrations (3.3, 11, and 28 mM) were assessed on adult islets only. Cellular mRNA levels for the mitochondrial DNA-encoded cytochrome b and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined by Northern-blot analysis. Enzymatic activities of high-Km (glucokinase) and low-Km (hexokinase) glucose-phosphorylating enzymes and succinate-cytochrome c reductase were also determined. Islets cultured at 3.3 mM glucose displayed a decreased activity of glucokinase compared with islets cultured at 28 mM glucose (23.3 +/- 12%), whereas there was no difference in hexokinase activity or the level of GAPDH mRNA. The activity of succinate-cytochrome c reductase was similar in islets cultured at the different glucose concentrations. The level of cytochrome b mRNA increased at 28 mM glucose compared with islets cultured at 11 mM glucose (140 +/- 14%). Islets incubated with streptozocin and subsequently cultured for 7 days at 11 mM glucose exhibited a decreased level of cytochrome b mRNA (65 +/- 5%) and no differences in the activities of glucokinase, hexokinase, succinate-cytochrome c reductase, or the level of GAPDH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The role of ascites and phospholipase A2 on peritoneal permeability changes in acute experimental pancreatitis.

Peritoneal permeability to fluorescein-isothiocyanate-conjugated (FITC) dextran, mol wt 10,000 was studied in acute experimental pancreatitis (AEP) in rats. The aim of the study was to elucidate the role of the pancreatitis ascites and its phospholipase A2 activity on the observed peritoneal permeability increase during AEP. Phospholipase A2 activity of ascites was 40 U/microL 1 h after the induction of AEP and decreased during the next 3 h gradually to a plateau of about 20 U/microL, where it remained to the end of the experiment at 24 h. A similar pattern was seen for protein, amylase, and lipase although the initial peak was most pronounced for lipase. Pancreatitis ascites did not--irrespective of its age (1 or 20 h) or incubation time (3-20 h)--affect the peritoneal transport of FITC dextran 10,000 in healthy rats. Similarly, intravenously-administered ascites and intraperitoneal instillation of pancreatic phospholipase A2 dissolved in saline were without effects. On the other hand, in another group of healthy animals, phospholipase dissolved in fresh pancreatitis ascites caused a statistically significant increase of peritoneal transport, as defined. In rats with pancreatitis, the addition of phospholipase A2 to the peritoneal fluid increased peritoneal transport of FITC dextran 10,000 as well as phospholipase A2 itself. We conclude that phospholipase A2 when instilled into the peritoneal cavity in the presence of pancreatitis ascites, has the ability to increase peritoneal permeability to FITC dextran 10,000 in healthy, as well as in pancreatitis rats. However, the phospholipase A2 activity of rat pancreatitis ascites is not sufficient for this mechanism to work. This, however, does not exclude its existence in other species, including humans.

Acute Disease↗

A novel effect of adenovirus VA RNA1 on cytoplasmic mRNA abundance.

Adenovirus VA RNA1 is a small RNA polymerase III transcript that enhances mRNA translation both in transfected cells and during a lytic virus infection. Here we present evidence that VA RNA1 also, in length-dependent manner, increases cytoplasmic mRNA abundance in transient expression assays in 293 cells.

Adenoviridae↗

Albumin, bradykinins, and eosinophil cationic protein on the nasal mucosal surface in patients with hay fever during natural allergen exposure.

This study examined plasma- and eosinophil-derived products in nasal lavage fluids obtained from patients with hay fever during natural allergen exposure. Nine patients with strictly seasonal allergic rhinitis and five normal, nonallergic subjects (control group) were studied. Nasal lavages were performed twice weekly, starting 1 week before the expected birch-pollen season and continuing for 6 weeks, thereby covering the entire birch-pollen season. Nasal symptoms and pollen counts were recorded daily. The lavage fluid was analyzed for it content of albumin, bradykinins, and eosinophil cationic protein (ECP). During the pollen season, each of these solutes was significantly increased in the nasal lavage fluid from the allergic patients (p less than 0.05) but not from the control subjects. Albumin, bradykinins, and ECP generally correlated better between themselves than with symptoms and pollen counts. We conclude that natural exposure to allergens induces plasma exudation and increased levels of ECP on the human nasal mucosa.

Adolescent↗

Lung cancer in women and type of dwelling in relation to radon exposure.

A case-control study based on interviews with 210 incident female lung cancer patients, 209 age-matched population controls, and 191 hospital controls was carried out in Stockholm county, Sweden. Radon measurements made in a sample of 303 dwellings, in which the study subjects had lived, showed that dwellings with ground contact had an average concentration of approximately 160 Bqm-3, twice the average concentration of other dwellings. A cumulated radon exposure index was calculated for each subject based on data from the interviews and the measurements. For the total group of lung cancer a relative risk (RR), adjusted for smoking, age, and degree of urbanization, of 1.8 (95% confidence interval: 1.2-2.9) and 1.7 (0.9-3.3) associated with "intermediate" and "high" exposure to radon was found. There was also a significant trend to a positive dose-response relationship (Ptrend = 0.03). For small cell cancer the corresponding figures for RRs were 1.9 (0.6-4.5) and 4.7 (1.5-14.2), respectively (Ptrend = 0.01). There seemed to be a positive interaction between radon exposure and smoking in relation to lung cancer. The findings indicate that domestic radon may be of importance for the induction of lung cancer, particularly for some histological types.

Aged↗

Increased peritoneal permeability in acute experimental pancreatitis.

The peritoneal permeability to differently sized dextran molecules; Mw 4,000, 10,000, 20,000, and 40,000 was investigated in rats with bile-induced acute pancreatitis. Following intraperitoneal deposition, repeated blood samples for measurement of the different dextrans were collected. The results showed increased peritoneal permeability to molecules between 4,000-20,000 daltons in animals with pancreatitis, whereas there was no significant difference for molecules of 40,000 daltons compared to healthy control animals. Also, the passage of phospholipase A2 (Mw 14,000) over the peritoneal membrane was increased during pancreatitis. It is suggested that the transperitoneal route may be of pathophysiological importance in the development of the systemic components of severe acute pancreatitis.

Acute Disease↗

Reversibility and reproducibility of histamine induced plasma leakage in nasal airways.

Plasma exudation is one cardinal factor in airways defence and inflammation. In inflammatory airway diseases such as rhinitis and asthma, however, plasma leakage may also have a pathogenetic role. Experimental data from animals indicate that highly sensitive, active, and reversible processes regulate the vascular and mucosal permeability to macromolecules. With the use of a nasal lavage model for the recovery of liquids on the mucosal surface the effect of histamine on the macromolecular permeability of the airway endothelial-epithelial barriers was studied in normal subjects. The concentrations of albumin, kinins, and N-alpha-beta-tosyl-L-arginine-methyl esterase (TAME) in nasal lavage fluid were measured and nasal symptoms assessed by a scoring technique. The reproducibility of three repeated challenges with 30 minute intervals on the same day was studied in 12 subjects and compared with the same procedure (three challenges) on a different day. Sneezing decreased significantly (p less than 0.05) after the first histamine challenge but was maintained thereafter. Otherwise, the mean values for symptoms and for markers of vascular leakage were very similar both for the three challenges in the same session and for the two challenge sessions on a different day. Sneezing, blockage, and secretions were associated with increased concentrations of TAME esterase (maximum 9000 cpm/ml), kinins (1.4 ng/ml), and albumin (0.3 g/l) in lavage fluid. Both the symptoms and the measures of plasma exudation were reversible and reproducible in the three repeat histamine challenges and at two challenge sessions on different days. These findings support the view that non-injurious, active processes regulate the inflammatory flow of macromolecules across airways endothelial-epithelial barriers. The present experimental approach would be suitable for studies of the modulatory effects of inflammatory stimulus induced plasma leakage and symptoms in human airways.

Adult↗

Objective monitoring of the allergic inflammatory response of the nasal mucosa in patients with hay fever during natural allergen exposure.

A method is presented for the objective monitoring of the inflammatory response of the nasal mucosa to natural allergen exposure through measurements of biochemical markers such as TAME-esterase activity in a daily nasal lavage. Nine patients with strictly seasonal allergic rhinitis caused by birch pollen and five healthy nonatopic control subjects participated in the present study, which started 1 wk before the birch pollen season and continued throughout the entire pollen season. A diary card was used to assess daily nasal symptoms, and a daily nasal lavage was performed once every afternoon. The degree of pollen exposure was assessed by daily pollen counts. The TAME-esterase activity in the lavage fluid from the allergic patients, but not in that from the nonallergic control subjects, increased significantly during pollen exposure despite low pollen counts and was found to correlate with daily nasal symptoms (r = 0.36; p less than 0.05) and the degree of pollen exposure (r = 0.45; p less than 0.01). The area under the curve for the daily TAME-esterase measurements thus differed significantly (p less than 0.02) between allergic patients (158 +/- 28) and control subjects (74 +/- 9). This approach for the monitoring of patients with hay fever during natural allergen exposure will make further objective studies on the pathophysiology and pharmacology of hay fever possible. We also provide support for the validity of previous findings obtained in allergen challenge situations utilizing the lavage approach.

Adult↗

Content of adenine nucleotide translocator mRNA in insulin-producing cells of different functional states.

This study was undertaken to characterize the expression of the gene coding for the adenine nucleotide translocator (ANT) in the insulin-producing beta-cell and to study any possible relationship between its expression and the functional state of the beta-cell. Adult and fetal rat pancreatic islets were prepared and cultured under different conditions in vitro. The total RNA from these islets and from the insulin-producing RINm5F cells was isolated and analyzed by the Northern blot technique via a cDNA clone (pAAC-9) coding for the bovine ANT. We found that a 1600-base pair (bp) mRNA hybridizing to the pAAC-9 clone could be detected in RINm5F cells, and a 1450-bp mRNA was similarly observed in the islets. These sizes correspond well to previously reported forms of mRNA for the ANT observed in other tissues. When comparing the intensities of the pAAC-9 hybridizing bands of the different islet groups, it was observed that fetal islets contained less of this mRNA than adult islets. Furthermore, the content of the ANT mRNA in adult islets cultured at a high glucose concentration was increased compared with islets cultured at a low glucose concentration. Finally, streptozocin-treated islets, which display an impaired glucose-sensitive insulin release after 6 days in culture, also contained less of this mRNA than the control islets. We conclude that pancreatic islet cells express an mRNA that appears to be highly homologous to the bovine ANT and that the contents of this mRNA increases with the functional status of the beta-cell. It is furthermore suggested that defects in the expression of this gene may be associated with impaired glucose sensitivity.

Animals↗