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Biomedical subjects

R Dahl

Publications and source records attributed to R Dahl.

At least 73 records · Page 4Linked to original sources

Audit-privilege laws: the right to know nothing?

In theory, environmental audit-privilege laws grant immunity to companies that uncover environmental problems during self-audits and that take steps to correct them so that information gleaned from such audits cannot be used against the company in a lawsuit. Supporters of audit-privilege laws believe these laws encourage more audits and more disclosures of regulatory violations because of the greatly reduced chances that audit findings will result in penalties. Opponents argue that in actuality, the level of audit activity in states that have audit-privilege or immunity laws is no different from that in the states without them and that companies in states with the laws are no more likely to disclose violations than companies in states without them. In addition, some citizens' groups, as well as the U.S. Environmental Protection Agency, continue to criticize the worst of the audit-privilege laws as measures that protect potential polluters.

Environmental Health↗

Transformation of hematopoietic cells by the Ski oncoprotein involves repression of retinoic acid receptor signaling.

The Ski oncogene has dramatic effects on the differentiation of several different cell types. It induces the differentiation of quail embryo cells into myoblasts and arrests the differentiation of chicken hematopoietic cells. The mechanism that Ski uses to carry out these disparate biological activities is unknown. However, we were struck by the similarity of these effects to those of certain members of the nuclear hormone receptor family. Both Ski and the thyroid hormone receptor-derived oncogene v-ErbA can arrest the differentiation of avian erythroblasts, and v-Ski-transformed avian multipotent progenitor cells resemble murine hematopoietic cells that express a dominant-negative form of the retinoic acid receptor, RARalpha. In this paper, we have tested the hypothesis that v-Ski and its cellular homologue c-Ski exert their effects by interfering with nuclear hormone receptor-induced transcription. We demonstrate that Ski associates with the RAR complex and can repress transcription from a retinoic acid response element. The physiological significance of this finding is demonstrated by the ability of high concentrations of a RARalpha-specific ligand to abolish v-Ski-induced transformation of the multipotent progenitors. These results strongly suggest that the ability of Ski to alter cell differentiation is caused in part by the modulation of RAR signaling pathways.

Animals↗

[Computer assisted neuropsychological testing of children].

The purpose of the study was to examine the feasibility of a computer-assisted neuro-psychological test program, the Neurobehavioral Evaluation System (NES), in six to seven year-old children. We administered three NES tests, Finger Tapping (FT), Continuous Performance Test (CPT) and Hand-Eye Coordination (HEC) to Faroese and Danish children. The FT and CPT were of appropriate difficulty, while the HE was too difficult for the majority of the children. Boys obtained better scores than the girls, and children who were familiar with computers and video games performed better than those without such experience. Older children also obtained better scores than younger ones, especially in the Faroese group. The Danish children performed better than the Faroese in FT and CPT. In HE there was no difference. The NES tests are feasible for children at this age, but appropriate comparison groups must be secured.

Child↗

Effects of five different airway smooth muscle relaxants on inhibitory neurotransmission in isolated guinea-pig trachea in vitro.

Pharmacodynamic effects produced by terbutaline (10 nM), theophylline (10 microM), sodium nitroprusside (30 nM), levcromakalim (0.3 microM) or isradipine (1 nM) on frequency-dependent relaxations induced by electric field stimulation of either proximal or distal parts of isolated guinea-pig trachea were studied in vitro. Preparations were depleted for tachykinins by capsaicin, pretreated with atropine (0.1 microM) and contracted by histamine (2 microM). Drug effects were studied in preparations with combined adrenergic and inhibitory non-adrenergic non-cholinergic (NANC) innervation and in preparations with inhibitory NANC innervation either with or without additional treatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (100 microM). In preparations with combined adrenergic and inhibitory NANC innervation terbutaline, sodium nitroprusside, levcromakalim and isradipine significantly reduced relaxant responses to electric field stimulation in proximal preparations, whereas distal preparations were only affected by terbutaline. In preparations with inhibitory NANC innervation without L-NAME pretreatment, terbutaline significantly enhanced relaxant responses to electric field stimulation only in distal preparations, whereas theophylline, sodium nitroprusside and levcromakalim significantly augmented responses to electric field stimulation in both proximal and distal preparations. In preparations with inhibitory NANC innervation pretreated with L-NAME, theophylline significantly inhibited relaxant responses in distal preparations, whereas sodium nitroprusside, levcromakalim and isradipine significantly augmented relaxant responses to electric field stimulation in proximal preparations. It was concluded that drugs used in the present study can modulate the effects of inhibitory autonomic and NANC neurotransmission in isolated guinea-pig trachea. Furthermore, it was shown that some variation in drug effects exists in relation to proximal and distal parts of guinea-pig trachea.

Animals↗

The Ski oncoprotein interacts with Skip, the human homolog of Drosophila Bx42.

The v-Ski avian retroviral oncogene is postulated to act as a transcription factor. Since protein-protein interactions have been shown to play an important role in the transcription process, we attempted to identify Ski protein partners with the yeast two-hybrid system. Using v-Ski sequence as bait, the human gene skip (Ski Interacting Protein) was identified as encoding a protein which interacts with both the cellular and viral forms of Ski in the two-hybrid system. Skip is highly homologous to the Drosophila melanogaster protein Bx42 which is found associated with chromatin in transcriptionally active puffs of salivary glands. The Ski-Skip interaction is potentially important in Ski's transforming activity since Skip was demonstrated to interact with a highly conserved region of Ski required for transforming activity. Like Ski, Skip is expressed in multiple tissue types and is localized to the cell nucleus.

Amino Acid Sequence↗

Anatomy, physiology and function of the nasal cavities in health and disease.

In studying drug absorption from the nasal mucous membrane, it is essential to have a clear understanding of anatomy and physiology of the nose, and how it relates to the characteristics of the delivery system used. The human nose is characterized by an individually varying shape and caliber, which might interfere with standard recommendations of intranasal medication. It is also of significance that there is a tendency for reflex- induced and profuse watery hypersecretion from glands, and for quick and considerable changes of mucosal thickness due to the presence of large venous sinusoids. These are factors which can interfere with pharmacokinetics. Also mucociliary transport rate has to be taken into consideration, as the drug is removed from the absorptive mucous membrane within 30 min. Intranasal drug distribution has been poorly studied in relation to nasal anatomy and pathology. In contrast to common believe, nasal inflammation does not seem to increase drug absorption. On the contrary, blockage, sneezing and rhinorrhoea might preclude the absorption.

Journal Article↗

[Voice signal analysis in laryngeal hyperreactivity].

Increased reactions of the laryngeal mucosal membrane can appear after acetylcholine (ACH) inhalation. A red mucous membrane, vocal cord edema, mucus formation, changes in the glottic configuration and (rarely) subglottic edema are visible to laryngoscopic observations. The influence on various voice parameters in patients with and without laryngeal hyperreactivity was researched in order to decide the reliability of voice parameter measurements in clinical practice. Significant variations of the soft phonation index (SPI), the fundamental frequency variation (vFo), the noise-to-harmonic ratio (NHR) and the voice turbulence index (VTI) were examined for their correlations with the observable features of laryngeal hyperreactivity. A single diagnosis of hyperreactivity with voice parameter analysis failed in 50% of the patients examined because of functional voice instability and irregularities seen. Only with both laryngoscopy for reliable discrimination and voice parameter analysis for quantitative registration were findings sufficient for assessing laryngeal hyperreactivity.

Acetylcholine↗

Psychopathology in the relatives of depressed-abused children.

OBJECTIVE: To determine if the type of symptomatology abused children manifest is related to family history of psychopathology. METHOD: Lifetime history of psychopathology was assessed in the relatives of 26 preadolescents--13 depressed abused (MDD-AB) and 13 depressed nonabused (MDD-NA) children. Rates of disorder in the relatives of these children were compared to published rates of psychopathology in relatives of 27 normal control (NC) children. Data were obtained on 104 first-degree relatives (MDD-AB = 25, MDD-NA = 29, NC = 50) and 503 second-degree relatives (MDD-AB = 127, MDD-NA = 117, NC = 259). The Schedule for Affective Disorders and Schizophrenia was used to assess psychopathology in parents, and Family History method was used to obtain lifetime psychiatric data for all other relatives. RESULTS: When compared to first-degree relatives of NC children, first-degree relatives of MDD-AB children had approximately a nine-fold increased risk for major depression, and a three- to nine-fold increased risk for other disorders associated with the familial subtype of affective illness known as Depression Spectrum Disease (e.g., antisocial personality, alcohol and substance dependence). Similar findings were reported in second-degree relatives, and comparisons between the relatives of MDD-NA and NC children. CONCLUSION: The findings extend results of prior research and (1) suggest familial vulnerability factors influence the symptom profile of abused children; and (2) highlight the value of incorporating psychiatric formulations into multidisciplinary models of child abuse research and treatment programs.

Adolescent↗

Blood eosinophil and monocyte counts are related to smoking and lung function.

The aim of this study was to investigate the predictive value of peripheral eosinophil and monocyte blood counts regarding lung function in smokers and non-smokers, and to investigate the influence of smoking on these cell counts. Forced expiratory volume in 1 s (FEV1) measurements and blood samples were collected from 298 non-atopic smokers and 136 never-smokers. Blood samples were repeated in 160 smokers after cessation of smoking (quitters) and 30 continuing smokers, 2, 6, 12 and 26 weeks after smoking cessation. Monocyte (P < 0.05) but not eosinophil blood counts were higher in never-smokers compared to smokers. In never-smokers, blood eosinophil counts and monocyte counts correlated inversely (P < 0.05) and directly (P < 0.01), respectively, with standardized FEV1 residuals (FEVR). In smokers, blood eosinophil (P < 0.05) and monocyte (P < 0.05) counts correlated directly with FEVR independent of smoking history. After smoking cessation, monocyte blood counts (P < 0.05) increased. Both eosinophil and monocyte blood counts showed a greater increase in quitters with decreased lung function (P < 0.05). Former heavy smokers had higher blood eosinophil (P < 0.05) but lower monocyte (P < 0.05) count increase than had former light smokers. These data suggest that smoking influences eosinophil and monocyte blood counts and that this is associated with a small negative effect on lung function. Eosinophil blood counts had an opposite relation to lung function in smokers and non-smokers. Further research should include investigations of relations between smoking and stimulatory factors for recruitment and activity of eosinophils and monocytes.

Adult↗

Effect of nasal inflammation and of intranasal anti-inflammatory treatment on bronchial asthma.

It is logical to look upon the nose and the bronchi as integrated parts of one 'united airway' and we would like to advance the hypothesis that optimal management of airway disease, caused by inhaled allergens, may necessitate control of inflammation in all parts of the airways. Nasal inflammation can aggravate asthma symptoms, and there is a rationale for giving intranasal anti-inflammatory treatment to patients with asthma. (i) Inhaled allergens are predominantly deposited in the nose, whether a patient suffers from rhinitis, asthma or both. (ii) Antigen presentation consequently takes place in the nose, and the response of the airway immune system is thus initiated in the nasal mucous membrane. (iii) Antigen presentation in the nose may possibly induce cell recruitment and activation not only in the nasal mucosa but also in the lower airways. (iv) Suppression of nasal inflammation may therefore be necessary for optimal management of asthma.

Administration, Inhalation↗

Prospective study on the effect of smoking and nicotine substitution on leucocyte blood counts and relation between blood leucocytes and lung function.

BACKGROUND: The influence of smoking and of nicotine substitution on the counts of total blood leucocytes and leucocyte subsets and the relations between the counts and lung function was investigated. METHODS: The study was a combined cross sectional and prospective study of 298 smokers and 136 non-smokers. Forced expiratory volume in one second (FEV1) was measured in all participants at baseline and six months after quitting smoking in 160 ex-smokers (quitters) and 138 persons with smoking relapse. Blood samples were obtained from all participants at baseline and from 160 quitters and 30 continuing smokers two, six, 12, and 26 weeks after smoking cessation and from 92 quitters one year after the cessation of smoking. RESULTS: Blood leucocyte counts and leucocyte subsets were all higher in smokers than in non-smokers. In cigarette smokers total leucocyte, neutrophil, and lymphocyte blood counts showed a dose dependent relationship with the daily cigarette consumption and pack years consumption. In smokers the neutrophil blood count was independently associated negatively with FEV1 residuals. After quitting smoking total leucocyte, neutrophil, and lymphocyte blood counts decreased during the first 26 weeks and after one year lymphocyte blood counts were higher than in non-smokers. In quitters substituted with nicotine chewing gum (2 mg) the accumulated number of pieces of chewing gum used in the 12 weeks had an inverse relationship with the decrease in the total lymphocyte blood count at 12 weeks after smoking cessation. CONCLUSIONS: Leucocyte blood counts are raised in smokers and decrease after smoking cessation. Neutrophil blood counts had an inverse relationship with lung function and nicotine may increase lymphocyte blood counts in smokers.

Chewing Gum↗

Bronchial reactivity to cigarette smoke in smokers: repeatability, relationship to methacholine reactivity, smoking and atopy.

Bronchial reactivity to cigarette smoke (CBR) in a cross-section of 98 smokers has been investigated. All participants were subjects to skin-prick tests to common allergens, lung function measurements and bronchial challenges with methacholine and cigarette smoke. In 38 participants a rechallenge with cigarettes was performed 1 h after the first cigarette challenge. Lung function indices analysed were: forced expiratory volume in one second (FEV1); maximal expiratory flow at 75% of the forced vital capacity (MEF75%); and forced mid-expiratory flow between 25 and 75% of the forced vital capacity (FEF(25-75%)). All participants were tested for asthma and allergy, and were required to provide information regarding respiratory symptoms, first degree relatives with asthma and allergy and smoking habits. A substantial decrease was seen in all lung function indices after 12 cigarette-smoke inhalations, but only FEV1 was related to other variables. The maximal mean percentage fall in FEV1 was 10%, which was directly related to the number of inhalations (p<0.05). In multiple regression analyses the percentage fall in FEV1 was directly related to: FEV1/vital capacity (VC) (p<0.01); to the asthmatic/bronchitic status (p<0.05); and to the accumulated and standardized cigarette consumption (p<0.05). The percentage fall in FEV1 bore no relationship to methacholine bronchial reactivity, sex or age and had a continuous distribution. The repeat challenge showed a smaller fall in FEV1 compared to the first challenge after 12 cigarette smoke inhalations (p<0.05). The percentage fall in FEV1 correlated after the first and the repeat challenge (p<0.05). Repeatability of the challenge could not be determined in this study because of tachyphylaxis. Bronchial reactivity to cigarette smoke is a tobacco smoke-specific bronchial response. All participants responded and the response showed a continuous distribution. Bronchial reactivity to cigarette smoke may be of importance for symptoms and prognosis in chronic bronchitis and chronic obstructive pulmonary disease and should be studied in relation to the degree of accelerated lung function loss in smokers and other cigarette induced lung abnormalities.

Asthma↗

Mechanisms of airflow limitation in the nose and lungs.

The main differences in the anatomies of the upper and lower airways are the vascular characteristics and bony surroundings of the upper airways compared with the smooth muscle component and the loose-lying situation of the lower airways. Both allergic asthma and rhinitis involve a similar process of mucosal inflammation in response to allergen exposure, characterized by inflammatory cell infiltration and local release of mediators. In addition, both the upper and lower airways are under similar influences from local neuronal reflexes, exercise, posture and cyclic variations. Challenge tests have been able to demonstrate the roles of the various influences and components in the inflammatory processes of asthma and allergic rhinitis. A particular difference in the response in asthma compared with rhinitis is the degree of non-specific hyperresponsiveness, which is a characteristic of the late response or response to repeated or prolonged exposure to allergen. Responsiveness of the bronchial mucosa in asthma patients is approximately 50 times that of normal (non-allergic or non-asthmatic) subjects, whereas that of the nasal mucosa in allergic rhinitis is only 2-8 times that of control subjects. The inflammatory process involved in hyperresponsiveness is similar in both conditions, involving increased infiltration of eosinophils and subsequent increased mediator release. The greater degree of hyperresponsiveness seen in asthma appears to be a consequence of the anatomical differences between the upper vs the lower airways. Evidence is presented for the contribution of increased airway wall thickness to the hyperresponsiveness in asthma, together with other possible factors, such as decoupling of responder tissue from surrounding tissue, increased smooth muscle contractility, and smooth muscle hypertrophy.

Allergens↗

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season.

BACKGROUND: The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon. METHODS: Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. (n=26), 0.2 mg o.d. (n=25), or placebo (n=12). Six healthy persons served as controls. RESULTS: During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001-P<0.05). Significant differences were seen between the steroid groups and the placebo group for all parameters (P<0.001-P<0.05). Higher eosinophil count (P<0.05), serum EPO (P<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001). CONCLUSIONS: Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.

Acute-Phase Proteins↗

Interaction between prostaglandins and selective phosphodiesterase inhibitors in isolated guinea-pig trachea in vitro.

The possible interaction between spontaneously synthesized relaxant prostaglandins and the relaxation produced by three different isoenzyme-selective phosphodiesterase inhibitors was investigated in the isolated guinea-pig trachea in vitro. The relaxant action of siguazodan (phosphodiesterase III inhibitor), rolipram (phosphodiesterase IV inhibitor) and zaprinast (phosphodiesterase V inhibitor) was investigated in preparations with either spontaneously tone alone or in preparations with spontaneous tone and additionally stimulated with histamine (1 microM). In addition, relaxant effects were assessed in preparations without spontaneous tone (inhibited by indomethacin 2 microM) and precontracted with histamine (1 microM) or prostaglandin F2 alpha (10 microM), either alone or in the presence of a non-relaxant concentration (20 nM) of prostaglandin E2. All three phosphodiesterase inhibitors preferentially relaxed preparations with spontaneous tone and showed increased relaxant effects in preparations with spontaneous tone and additionally stimulated with histamine compared to preparations contracted by histamine alone. This enhanced relaxing effect observed in the presence of initial spontaneous tone was mimicked by exogenous application of prostaglandin E2 to indomethacin treated preparations either precontracted by histamine or prostaglandin F2 alpha. Furthermore, the study revealed marked differences in the relaxant profiles of siguazodan, rolipram and zaprinast, differences which most likely are related to the functional importance of the phosphodiesterase isoenzymes inhibited by these drugs. It is concluded that endogenously synthesized relaxant prostaglandins and exogenously applied prostaglandin E2 are capable of enhancing the relaxant action of the phosphodiesterase inhibitors siguazodan, rolipram and zaprinast and that cyclooxygenase inhibition is an important way to avoid this interaction in experimental studies of airway smooth muscle relaxants in isolated guinea-pig trachea in vitro.

Animals↗