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Biomedical subjects

U Alkner

Publications and source records attributed to U Alkner.

34 records · Page 2Linked to original sources
PubMed1992

Topical vasoconstrictor (oxymetazoline) does not affect histamine-induced mucosal exudation of plasma in human nasal airways.

Mucosal exudation of almost unfiltered plasma proteins, plasma-derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine-induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double-blind, randomized, cross-over and placebo-controlled study with pretreatment with a single dose oxymetazoline chloride (5 micrograms or 50 micrograms; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min, and three histamine challenges were performed at 30-min intervals during this period. The concentrations of two exudative indices, N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique. Histamine induced all three symptoms with correlatively raised levels of the biochemical markers for plasma exudation. Oxymetazoline chloride caused a significant decrease in nasal stuffiness, but did not influence the other nasal symptoms or the histamine-induced plasma exudation. It is concluded that histamine-induced plasma exudation is not influenced by topical oxymetazoline. Thus, an important airway defence reaction such as plasma exudation may be little affected by topical alpha-adrenoreceptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1992

The effect of non-immune IgG on antigen-antibody complexation.

Two preparations of human IgG, one acylated with beta-propiolactone (acylated IgG) and one treated at pH 4 with traces of pepsin (pH 4-IgG), were used to study the effect of non-immune IgG on antigen-antibody interactions in the antigen excess zone. Employing two immunological methods together with size-exclusion chromatography, we found that the formation of human albumin-rabbit anti-human albumin complexes was inhibited in the presence of human IgG. In addition, IgG seemed to promote the aggregation of already formed complexes. Thus, non-immune IgG may modulate immune complexation by direct molecular interactions. The effect was dependent on the size and composition of the immune complexes as well as on the conformation of the IgG molecules with respect to their shape, isotype, charge, and other surface properties. Some possible mechanisms for the reactions are discussed.

Acylation↗
PubMed1992

Bronchial exudation of bulk plasma at allergen challenge in allergic asthma.

This study examined plasma exudation into the bronchial lumen after allergen challenge. A novel low-trauma technique was developed to challenge and lavage a medium-sized lingular or middle lobe bronchus. Eleven subjects with challenge-assessed pollen-sensitive asthma were allocated to fiberbronchoscopy in the supine position. In the control bronchus 0.5 ml diluent was instilled. The bronchus was occluded proximally 3 min later by inflation of a balloon, and lavage was carried out twice with 25 ml saline. Incremental doses of allergen solution (0.5 ml) were then instilled in the contralateral lung. The challenge continued until a clearly visible bronchial reaction occurred and was immediately followed by the same lavage as on the control side. The lavage liquids were analyzed for the presence of plasma exudation and mast cell activation indices. On the allergen-challenged side, tryptase, reflecting mast cell activation, was increased by 150% (p < 0.01) compared with the control side. Fibrinogen (mol wt 340,000), reflecting large protein exudation, was increased by 840% (p < 0.05), and N-alpha-tosyl-L-arginine-methyl esterase activity, reflecting both large protein exudation and mast cell activation, increased by 480% (p < 0.01). The level of albumin (mol wt 69,000), the major luminal protein under baseline conditions, increased but not significantly. We conclude that activation of mast cells and luminal entry of little sieved plasma exudates occur early after endobronchial allergen provocation in human subjects with allergic asthma.

Albumins↗
PubMed1991

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↗
PubMed1990

Systemic and intraocular uptake of spantide, a tachykinin antagonist, following topical application to the rabbit eye.

Previous observations have indicated that topical application to the rabbit eye of tachykinin antagonists, including spantide, effectively prevents the miosis and the disruption of the blood-aqueous barrier consequent to ocular injury. The present study shows that spantide is taken up into the rabbit eye following topical application. This was established by determination of spantide in the aqueous humor by radioimmunoassay. The concentrations reached in the aqueous humor were those that could be expected to block tachykinin receptors. The elimination of spantide from the aqueous humor was found to be slow. From HPLC analysis it seemed that spantide in the aqueous humor is degraded to smaller products, predominantly spantide 5-11. Some of the topically applied peptide appeared in the general circulation. Here the rate of elimination was rapid by comparison. Very small amounts of spantide appeared in the cerebrospinal fluid after intravenous injection.

Administration, Topical↗
PubMed1990

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↗
PubMed1990

The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions.

A 'nasal pool' (NP) device, a compressible plastic container with an adapted nozzle, was used to perform a continuous 10-min nasal provocation and lavage. This novel technique brings known concentrations of agents into contact with a large and defined area of the nasal mucosal surface for extended periods of time. Simultaneously, the surface exudations/secretions of the same nasal mucosa are effectively sampled by the NP fluid. A concentration-response study of histamine (80, 400 and 2000 micrograms/ml) was performed in 12 normal subjects on three different occasions. Exudation of plasma albumin into the lavage fluid was measured to quantitate the histamine-induced airway inflammation. The effect of the dwell time on exudation was examined using histamine (400 micrograms/ml) instilled in the nasal cavity for time periods from 10 sec to 10 min. The time course of histamine-induced plasma exudation response was studied by exposing the mucosa to histamine (400 micrograms/ml) for 12 min, with the NP renewed every minute. Allergen-provocations were performed in subjects with hay fever and TAME-esterase activity in the returned lavage fluid was determined to indicate the degree of response. Histamine produced a concentration-dependent increase in albumin levels in the NP fluid; 123.3 +/- 25.6, 213.8 +/- 19.7 and 430.2 +/- 32.0 micrograms/ml (mean +/- s.e.m.), respectively. The time-course study demonstrated that plasma exudation into the lumen occurred promptly and that the exudation response reached a maximum after exposure to histamine for 6-10 min. The dwell-time experiments supported this finding. After 10 min the exudation appeared to decline despite the continued presence of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

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↗
PubMed1988

Development of an immunoassay for glypressin, an N-terminal extended vasopressin analogue.

The development and evaluation of a radioimmunoassay for N alpha-tri-glycyl-lysine8-vasopressin is described. The site of hapten conjugation of the immunogen has been controlled and the use of various radiolabelled tracers has been evaluated with special reference to the site of iodination. The most extensively studied antiserum showed specificity for the N-terminal triglycyl-extension as well as for several amino acid residues of the vasopressin ring. It crossreacted 27%, 28%, and 0.3% with Lys8-vasopressin, arg8-vasopressin and oxytocin respectively, and it was used to quantify triglycyl-lysine8-vasopressin in human plasma after SepPak C18 extraction. The sensitivity of the assay was 5 pg/tube with an intra-assay CV of 5-6% at 17 and 70 pg/tube. The identity of the immunoreactivity was studied by reversed phase chromatography.

Animals↗
PubMed1986

Intranasal administration of peptides: nasal deposition, biological response, and absorption of desmopressin.

The nasal administration of desmopressin [1-(3-mercaptopropionic acid)-8-D-arginine-vasopressin] in humans was investigated. Desmopressin solutions containing 99mTc-labeled human serum albumin were administered intranasally as a spray, using two metered-dose pumps, or as drops, using a rhinyle catheter or a single-dose pipet. Images of the sites of deposition and rates of clearance were monitored quantitatively by gamma scintigraphy. Plasma levels of desmopressin were measured using a highly sensitive and specific radioimmunoassay. The biological response was determined by measuring circulating levels of F VIII, the antihemophilia factor. The sprays were deposited mainly anteriorly, from which small portions were cleared slowly into the nasal pharynx. In contrast, the drops were deposited mostly posteriorly and cleared very rapidly in large portions; some were swallowed immediately. Plasma levels showed that desmopressin was absorbed to a greater extent after administration of the spray with a 2 to 3-fold increase in the relative bioavailability compared with the drops. The biological response was clearly enhanced after spray administration and produced similar increases in F VIII activity. A linear correlation was observed between maximum plasma desmopressin levels and maximum F VIII activity. The use of an intranasal spray device can deposit well-controlled doses within the nasal cavity, which remain there sufficiently long to provide a clear enhancement in absorption and bioavailability.

Absorption↗
PubMed1983

Dissociation of soluble antigen-antibody complexes by rheumatoid factor IgM.

Intact rheumatoid factor (RF)-active IgM dissociated soluble antigen-antibody complexes formed in the antigen excess zone, whereas trypsin-digested protein had less effect. The dissociation mechanism involved an interaction between the RF IgM and the Fc gamma of antibodies in the complexes. RF-active IgM had no demonstrable effect on antigen-antibody complexes when the antigen or the antibody had been immobilized. This was true irrespective of whether the experiments were performed in the antigen or in the antibody excess zone and despite binding between RF IgM and the immobilized proteins.

Animals↗
PubMed1983

Factors affecting IgA related hyperviscosity.

Sera from 14 patients with an IgA M-component, six of whom had myelomatosis and eight with benign monoclonal gammopathy (BMG) were analysed. All six sera from patients with high IgA (greater than 40 g/l) and total protein (greater than 100 g/l) concentrations were hyperviscous (HV). Four of these six patients also had hyperviscosity syndrome (HVS). There was no correlation between the quantity of IgA dimers or polymers and the presentation of HV and HVS. The binding between IgA and albumin and alpha 1-anti-trypsin was not covalent. Differences in the microenvironment of S-S bonds or of aromatic amino acids between isolated monoclonal monomeric and dimeric IgA were demonstrated with circular dichroism. Besides that, differences in hydrophobicity (exposure of aromatic amino acids) between IgA from normal serum and monomeric and dimeric IgA from a myeloma serum were revealed using hydrophobic interaction chromatography. The significance of hydrophobic interactions involving IgA and the influence of such forces on the circulation of the molecules are discussed.

Blood Proteins↗
PubMed1982

Circular dichroism of immune complexes with rheumatoid factor activity.

The circular dichroism (CD) of IgG complexes with RF activity and that of monomeric IgG without this activity, and isolated from the same individual, were compared. The IgG complexes had a significantly deviant CD spectrum in the near u.v. region, both before and after dissociation, whereas the monomeric IgG had a normal spectrum. Immunoglobulins were isolated from the same serum with the use of specific antiserum against unique determinants in some IgG complexes with RF activity. Both before and after dissociation the CD spectrum in the far u.v. region of these immunoglobulins differed significantly from that of the above-mentioned preparations. The results confirmed that the structure of IgG in the RF-active complexes differed from that of normal IgG. The immunoglobulins with the unique determinants had, in turn, a structure that was not found in the pool of the RF-active IgG molecules or in normal IgG.

Antigen-Antibody Complex↗
PubMed1981

Isolation and characterization of intermediate complexes and other components with common antigenic determinants.

Fractions with affinity for heat-denatured human IgG (HDG) were isolated from four sera that contained intermediate complexes (IC). These IC fractions contained part of the 75 IgG, all IC, and part of the rapidly sedimenting complexes (RC) found in the sera. The IC consisted of IgG1 or IgG3 and the RC of IgG and IgM with kappa and lambda light chains. The IgG in the IC fractions contained an abnormally large amount of neuraminic acid. No correlation between IgG subclass or content of neuraminic aid and complex formation was found. There were indications that the formation of IC was not only the result of self-association of IgG molecules with anit-gamma-globulin activity. Specific rabbit antisera were prepared against two of the IC fractions. Affinity chromatography wtih immobilized IgG and F(ab')2gamma from these antisera confirmed the presence of common antigenic determinants in the sera. These determinants occurred mainly in 7S components in one individual, in IC in one and in RC in another. Only a minor part of the serum components with affinity for HDG contained the determinants. RF activity was found in the components that lacked and in those that contained the common antigenic determinants.

Antigen-Antibody Complex↗
PubMed1979

Effect of IgM fractions with or without rheumatoid factor activity on antigen-antibody reactions.

The effect of isolated IgM fractions, with or without rheumatoid factor (RF) activity, on reactions between human albumin and rabbit anti-human albumin, human IgG and rabbit anti-human IgG, and tetanus toxoid and human anti-tetanus toxoid was assessed in the antigen excess zone. RF-active fractions increased and RF-negative IgM fractions decreased the amount of free antigen. The immune complexes that were affected by RF IgM fractions differed in composition from those affected by normal IgM fractions.

Antigen-Antibody Complex↗