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R Dahl

Publications and source records attributed to R Dahl.

At least 91 records · Page 5Linked to original sources
PubMed1997

In vitro studies on the interactions of beta2-adrenoceptor agonists, methylxanthines, Ca2+-channel blockers, K+-channel openers and other airway smooth muscle relaxants in isolated guinea-pig trachea.

Pharmacodynamic interactions in vitro between different types of airway smooth muscle relaxants were systematically and quantitatively evaluated by using a new methodological technique. Relaxant concentration-effect curves for terbutaline, theophylline, cromakalim, sodium nitroprusside and isradipine were obtained in isolated guinea-pig trachea contracted by histamine (1 microM). The effects of three different fixed concentrations of each airway smooth muscle relaxant were initially attained and concentration-effect curves for combinations with increasing concentrations of either one of the other relaxants were produced. Based on pharmacodynamic parameters obtained by non-linear regression analysis of experimental data for the relaxants alone theoretical concentration-effect curves for predicted additive interaction were constructed by using the isobolic method. Synergistic (over-additive) interaction was defined as existing when data points and derived pharmacodynamic parameters obtained with combinations of the relaxants showed statistically significant deviation from the predicted additive interaction curve and its functional parameters. Significant synergistic interaction with terbutaline was found for both theophylline (70 or 200 microM), cromakalim (0.1, 0.3 or 1 microM), sodium nitroprusside (30 or 100 nM) and isradipine (1, 3 or 10 nM). Theophylline showed synergistic interaction with cromakalim (0.1, 0.3 or 1 microM), sodium nitroprusside (10 nM) and isradipine (1, 3 or 10 nM). Interactions between cromakalim and sodium nitroprusside (10, 30 or 100 nM) were also synergistic, whereas cromakalim and isradipine (1, 3 or 10 nM) produced only additive interaction. Possible mechanisms underlying the interactions are discussed on basis of existing knowledge with special regards to phosphodiesterase isoenzymes, K+ and Ca2+ channels.

Adrenergic beta-Agonists↗
PubMed1997

Sample preparation and DNA extraction procedures for polymerase chain reaction identification of Listeria monocytogenes in seafoods.

Five grams of seafood products were inoculated with one to 500 viable or 10(9) heat-killed cells of Listeria monocytogenes. The presence of the pathogen was detected by the polymerase chain reaction (PCR) with primers specific for fragments of the listeriolysin O (hly) gene (two sets) and for the invasion-associated protein (iap) gene (one set). For DNA preparation, boiling, either alone or in combination with lysozyme and proteinase K treatment, was not always sufficient to lyse L. monocytogenes, while treatment with Triton X-100 produced consistently good DNA suitable for amplification. To avoid false-negative and false-positive results, 48 h incubations were necessary and a subculturing step after an initial 24 h incubation greatly improved the results. The primers that amplified regions of the listeriolysin O gene gave clearer and stronger products than primers for the invasion-associated protein gene. Using this method we were able to detect one to five L. monocytogenes cells in 5 g of product in a total of 55 h.

Animals↗
PubMed1997

Monitoring of bronchial asthma.

Assessment of asthma severity is important for disease management. Analysis of symptoms past and present, and previous and actual lung function measurements (including variability) is the usual method of evaluation and classification of asthma disease severity and activity. However, symptoms and lung function alterations are the result of pathophysiological processes including inflammation in the bronchial wall which, in chronic phases, precedes the clinical measurements, and are risk factors for disease progression and worsening. Tools for more precise determination of asthma disease processes in the airway wall would be of importance for prophylactic intervention to avoid chronic damage to the airways and acute worsenings to occur.

Asthma↗
PubMed1997

Predictors of early- and late-phase reactions to bronchial allergen challenge.

The influence of inhaled steroids and predictive factors on the response to bronchial allergen challenge (BCA) was evaluated in 80 asthmatics allergic to Dermatophagoides pteronyssinus (Der p). All underwent BCA with Der p and measurement of early (EAR) and late asthmatic reaction (LAR). The cumulative dose of allergen producing 20% fall in FEV1 in the EAR (PD20) was calculated. Bronchial histamine provocation, conjunctival provocation test (CPT), and skin prick test with Der p extract were performed. Specific IgE to Der p in serum (RAST), blood eosinophil (EOS) count, serum eosinophil cationic protein, and eosinophil protein X were measured. Thirty patients (38%) were treated with inhaled steroids. All patients had at least a 20% fall in FEV1 in EAR. Some 42% of nonsteroid- and 33% of steroid-treated patients had LAR with fall in peak flow of at least 20%. For patients not treated with steroid, 35% of variation in PD20 was explained by RAST and histamine reactivity, and 53% of variation of observed PD20 could be predicted. The baseline FEV1, EOS, and EAR explained 28% of variation in LAR, and 28% of variation in observed LAR could be predicted. For patients treated with steroids, 38% of variation in PD20 was explained by EOS and histamine reactivity, and only 18% of variation of observed PD20 could be predicted. For patients treated with steroids, it was impossible to predict LAR. We conclude that to achieve a quantitative estimation of allergen-specific EAR and LAR, BCA cannot be replaced by the tests used in this study. Treatment with inhaled steroids modifies the response to BCA, making quantitative prediction of EAR less accurate and prediction of the magnitude of LAR impossible.

Administration, Inhalation↗
PubMed1997

Effect of corticosteroids on nasal blockage in rhinitis measured by objective methods.

This paper gives an overview of placebo-controlled studies of the effect of corticosteroid treatment on nasal blockage, based on objective measurements of nasal airway patency. A few studies of perennial rhinitis have indicated that pretreatment with an intranasal corticosteroid has a moderate effect on nasal hyperresponsiveness, measured as the histamine-induced increase of nasal blockage. Whereas the effect on allergen-induced early-phase symptoms is variable, the effect on the late-phase blockage is almost complete. In seasonal allergic rhinitis, a few studies have shown an effect of intranasal steroids on nasal airway resistance, nasal peak flow and on acoustic rhinometry, but there are no reports on the effect in adults with perennial rhinitis. In children with perennial disease, intranasal treatment results in increased nasal patency and, in one study, also in reduced mouth breathing and in an increased threshold for exercise-induced bronchoconstriction. In patients with nasal polyposis, intranasal steroids have an effect on nasal airway resistance and on nasal peak flow both before and after polypectomy. There is convincing evidence that intranasal corticosteroids provide a better effect than antihistamine on nasal blockage. Amazingly, there does not appear to be any report on the effect of systemic corticosteroid treatment on nasal airway patency, and it is therefore difficult to recommend this treatment in a rational dosage. In conclusion, there is a fairly good documentation in support of the efficacy of intranasal steroid treatment on nasal airway patency in rhinitis. An objective measurement of nasal airway patency ought to be the routine in controlled rhinitis trials.

Adrenal Cortex Hormones↗
PubMed1997

Cellular mechanism of aminoglycoside tolerance in long-term gentamicin treatment.

In the rat, nephrotoxicity results from uptake of gentamicin at the apical membrane of proximal tubule (PT) cells. However, during continuous gentamicin treatment, the PT epithelium has been shown to recover. The mechanism(s) of cellular recovery and development of tolerance remains unknown. Therefore, we undertook studies designed to characterize cellular adaptations that occur during long-term gentamicin (LTG) treatment. After 19 days of gentamicin treatment, electron microscopy morphological evaluation revealed cellular recovery with an apparent mild decrease in height and number of microvilli. Enzymatic analysis of LTG PT membranes showed that apical and basolateral membranes had essentially returned to normal. Analysis of apical membrane lipid content revealed persistent statistically significant (P < 0.01) elevations in phosphatidylinositol (PI). In vivo immunogold morphological studies and biochemical studies in LTG rats revealed that endocytosis of gentamicin was selectively reduced, whereas the markers of fluid-phase (horseradish peroxidase) and receptor-mediated (beta2-microglobulin) endocytoses were unaffected or increased. Biochemical analysis showed that, although gentamicin binding to apical membranes isolated from LTG rats increased greater than twofold (P < 0.05) over membranes from untreated rats, in vivo cellular uptake, quantified with [3H]gentamicin, was reduced. Western blot analysis of LTG apical membranes and immunofluorescent staining of perfusion-fixed LTG kidneys showed no change in megalin levels or its apical membrane localization. These data imply that recovery of PT cells from and tolerance to LTG treatment involve a selective inhibition of gentamicin uptake across the apical membrane. They indicate that the mediators of gentamicin endocytosis were affected differently: PI levels increased, whereas megalin levels did not change. We conclude that selective inhibition of gentamicin uptake during LTG treatment is not affected by a reduction in PI or megalin levels. We postulate that trafficking of gentamicin and/or gentamicin-containing endocytic structures is reduced in LTG rats, allowing cells to develop tolerance to gentamicin.

Adaptation, Physiological↗
PubMed1997

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Chemical Industry↗
PubMed1996

Increased hepatic Na,K-ATPase activity during hepatic regeneration is associated with induction of the beta1-subunit and expression on the bile canalicular domain.

Cellular and molecular mechanisms regulating the activity of the sodium pump or Na,K-ATPase during proliferation of hepatocytes following 70% liver resection have not been defined. Na,K-ATPase may be regulated by synthesis of its alpha- and beta-subunits, by sorting to either the sinusoidal or apical plasma membrane domains, or by increasing membrane lipid fluidity. This study investigated the time course of changes during hepatic regeneration for Na, K-ATPase activity, lipid composition and fluidity, and protein content of liver plasma membrane subfractions. As early as 4 h after hepatic resection, Na,K-ATPase activity was increased selectively in the bile canalicular fraction. It reached a new steady state at 12 h and remained elevated for 2 days. Although hepatic regeneration was associated with a reduced cholesterol/phospholipid molar ratio and increased fluidity, measured with two different probes, these changes in lipid metabolism were in the sinusoidal membrane domain. The Na,K-ATPase beta1-subunit, but not the alpha1-subunit, was increased selectively at the bile canalicular surface as shown by immunoblotting of liver plasma membrane subfractions and the morphological demonstration at both the light and electron microscopic levels. Furthermore, cycloheximide blocked the rise in beta1-subunit mRNA levels. Since the time course for beta1-subunit accumulation was similar to that for activation of Na,K-ATPase activity, this change implicated the beta1-subunit in activating sodium pump activity.

Animals↗
PubMed1996

Human blood eosinophils produce and secrete interleukin 4.

Interleukin 4 (Il-4) is an immunoregulatory cytokine which induces T-cell proliferation and differentiation into a Th2 phenotype, and is of particular importance for the induction of IgE synthesis. In the present study, the capability of human peripheral blood eosinophils from allergic and non-allergic donors to produce Il-4 was examined. Using reverse transcribed polymerase chain reaction (RT-PCR), it was shown that highly purified eosinophils from allergic patients express mRNA for Il-4. Resting eosinophils also gave specific immunoreactivity with anti-Il-4 antibodies, consistent with translation of Il-4 mRNA. Light and electron microscopic immunocytochemistry revealed that Il-4 was prestored in the eosinophilic granules. These results were confirmed by Il-4 specific ELISA which showed that Il-4 production could be upregulated in the eosinophils and released from the eosinophils following stimulation with the calcium ionophore A23187. These data indicate that eosinophils may be an important source of Il-4 at sites of allergic inflammation. Thus, eosinophils may act as immunomodulatory cells enhancing the allergic response through formation of Th2-cells and inducing the isotype switching to IgE in human B-cells.

Base Sequence↗
PubMed1996

Fluorodopa positron emission tomography with an inhibitor of catechol-O-methyltransferase: effect of the plasma 3-O-methyldopa fraction on data analysis.

Flurodopa (FDOPA) is an analogue of L-di-hydroxyphenylalanine (L-dopa) used to assess the nigrostriatal dopamine system in vivo with positron emission tomography (PET). However, FDOPA/PET quantitation is complicated by the presence of the 3-O-methyl-FDOPA (3OMFD) fraction in brain and plasma. Pretreatment with entacapone (OR-611), a peripheral catechol O-methyl-transferase (COMT) inhibitor, greatly reduces the plasma 3OMFD fraction and provides an ideal situation to evaluate the contribution of the plasma 3OMFD fraction in several kinetic models of FDOPA uptake. We performed FDOPA/PET with and without the OR-611 preadministration in six Parkinson's disease (PD) patients. We measured the time-course of the plasma FDOPA and 3OMFD fractions using high-pressure liquid chromatography (HPLC). We calculated striato-occipital ratios (SOR), and estimated the striatal FDOPA uptake rate constant graphically using the plasma FDOPA and occipital tissue time activity curves (KiFD and KiOCC, respectively). We also estimated striatal dopa decarboxylase (DDC) activity (k3D) using a model incorporating independent measurements of 3OMFD transport kinetic rate constants. With the preadministration of OR-611, the pharmacological efficiency in plasma was prolonged significantly (21.1-37.7%; p < 0.01). We also observed significant mean elevations in SOR and KiOCC by 21.8 and 53.5%, respectively (p < 0.05). KiFD and k3D did not show significant change. We conclude that OR-611 prolongs the circulation time of FDOPA in the plasma but does not alter rate constants for striatal FDOPA uptake or decarboxylation.

Adult↗
PubMed1996

The rationale for use of topical corticosteroids in allergic rhinitis.

The rationale for using topical corticosteroids in the treatment of allergic rhinitis is that high drug concentrations can be achieved at receptor sites in the nasal mucosa, with minimal risk of systemic adverse effects. Topical corticosteroids have been demonstrated to reduce the number of Langerhans' cells (or their markers) in the nasal mucosa, and this is thought to attenuate antigen presentation. T lymphocytes have been identified as being significant in orchestrating the immune-inflammatory response, particularly the TH2 cells, which represent an important target for topical corticosteroids. TH2 cell-evoked mast cells and basophils are the sole producers of histamine, a mediator of major importance for rhinitis symptoms. Several studies have shown that the increased number of mast cells and basophils in the epithelium following antigen challenge/exposure, are markedly reduced by topical corticosteroids. Furthermore, the number of eosinophils, an important morphological marker of allergic rhinitis, can be profoundly reduced by treatment with topical corticosteroids. The rationale for topical treatment is strengthened by evidence of inhibition of cytokine release from surface epithelial cells, resulting in reduced recruitment and activation of mast cells, basophils, and eosinophils, which may be attributed to the high drug concentration achieved in epithelial cells. Ongoing inflammation in the mucous membrane is indicated by entry of plasma into the nasal lumen which subsides with the anti-inflammatory efficacy of topical corticosteroids. In contrast to antihistamine therapy, which has little effect on nasal blockage, pretreatment with topical corticosteroids results in almost complete attenuation of late-phase symptoms including nasal blockage, and moderate efficacy in early phase symptoms. Clearly, the spectrum of anti-inflammatory activity afforded by topical corticosteroid therapy is of clinical significance in reducing the three major symptoms of allergic rhinitis- sneezing, watery rhinorrhoea and nasal blockage.

Administration, Intranasal↗
PubMed1996

Challenge tests in nose and bronchi: pharmacological modulation of rhinitis and asthma.

In order to study the pathophysiology of allergic airway disease and its response to pharmacotherapy, allergic and non-allergic provocation challenge techniques can be employed. Lower airway challenge has been used widely, but the use of nasal challenge is becoming more widespread as its advantages are realized. New measurement techniques are also being used (e.g. acoustic rhinometry), along with more classical methods such as spirometry, peak airflow rate and symptom scores, to determine the response to challenge. In the lungs, allergen challenge produces a biphasic response, which is less clearly defined in the nose. Topical histamine challenge closely resembles the effects of an allergic reaction and acts by stimulating sensory nerve endings. Methacholine is also often used for nasal challenge (often in addition to histamine), due to its effects on glandular sensitivity. Exercise induces bronchoconstriction in asthmatics and can be imitated by inhalation of cold, dry air. Cold air induces glandular hypersecretion and nasal discharge in normal subjects, which is increased in severity in rhinitic patients. Drug effect investigations using antihistamines have shown that histamine is important in producing the symptom of sneezing, whereas nasal blockage is due to vasodilatation rather than plasma exudation and oedema. Beta 2-agonists reduce allergen-induced symptoms by stabilizing mast cells, whereas cholinoceptor antagonists reduce watery nasal secretion. Increased responsiveness of sensory nerves and nasal glands is a characteristic clinical feature of asthma and rhinitis, which is responsible for the symptomatology. These effects can be reduced by topical corticosteroids.

Asthma↗
PubMed1996

Cytogenetic and clinical characteristics of a case involving complete duplication of Xpter-->Xq13.

True isochromosomes for Xp probably do not exist in a liveborn. We describe a rare case of complete Xp duplication and retention of the inactivation centre at Xq13. Cytogenetically, it is described as a nonmosaic 46,X,psu idic(X)(q13). Complete duplication of Xpter-->Xq13 was confirmed by banded analysis and FISH probes for X centromere, Xp21, XIST locus, and whole chromosome paints for X and Y. The abnormal X was always late replicating. Clinically, the patient was short statured, had primary amenorrhoea, and incomplete development of secondary sexual characteristics, but otherwise was phenotypically normal. There are no non-mosaic reported cases with complete duplication of i(Xp) confirmed by FISH or molecular techniques. Those cases with partial duplication of Xp and presence of the inactivation centre share the traits of amenorrhoea and poor secondary sexual development. To develop a clinical profile of duplication of Xp (in presence of Xq13) there is a need to study more cases.

Adult↗
PubMed1996

Cellular ATP depletion induces disruption of the spectrin cytoskeletal network.

Ischemia in vivo or ATP depletion in vitro result in disruption and cellular redistribution of the cortical F-actin cytoskeleton in epithelial cells. However, little is known regarding the effect of these two maneuvers on other components of the actin cytoskeleton. Because the spectrin (fodrin in epithelial cells)-based network links the actin cytoskeleton to the surface membrane, we have utilized a reversible model of ATP depletion in LLC-PK1 cells to study the effect of ATP depletion on fodrin and ankyrin. Under physiological conditions, both ankyrin and fodrin were largely Triton X-100 insoluble and colocalized immunofluorescently along the lateral membranes of LLC-PK1 cells. After ATP depletion, there was a rapid and duration-dependent increase in Triton X-100 solubility of both proteins. This was not true for villin and myosin 1, as Triton X-100 solubility was unaffected and reduced by ATP depletion, respectively. The increase in fodrin and ankyrin detergent solubility during ATP depletion was associated with cytosolic redistribution of the proteins, as determined using immunofluorescent techniques. Sucrose gradient fractionation and Western blot analysis of the Triton X-100-soluble fraction following ATP depletion revealed lack of association between fodrin and ankyrin. Furthermore, dual-label digital confocal immunofluorescent studies revealed lack of association of cytoplasmic ankyrin and fodrin following ATP depletion. Taken together, these data indicate that ATP depletion in LLC-PK1 cells leads to dissociation of both ankyrin and fodrin from the actin cytoskeleton. Furthermore, the two proteins dissociate from each other and redistribute throughout the cytoplasm.

Actins↗