A comparative study of venous occlusion and DDAVP stimulated fibrinolysis in normolipidemic subjects.
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Biomedical subjects
Publications and source records attributed to P Andersen.
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(1) The effect of active and inactive phorbol esters on synaptic transmission and on membrane properties of CA1 pyramidal cells in hippocampus have been analyzed by intracellular recording. (2) 4 beta-phorbol-12,13 dibutyrate (beta PDBu), but not the alpha-isomer, increased the firing probability, reduced the spike latency and enhanced the EPSP amplitude in response to synaptic activation. The effect was similar to the changes seen in long term potentiation. After alpha PDBu addition it was possible to elicit further enhancement by tetanization, but not after beta PDBu administration. (3) A slowly developing hyperpolarization was seen after active phorbol ester application without apparent changes in the soma input resistance. (4) Active phorbol esters reduced the slow afterhyperpolarization (AHP) in these cells without affecting the intermediate AHP.
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The effect of inhaled beclomethasone dipropionate and budesonide on the adrenal function was studied in 30 children (aged 7 to 15 years) with mild bronchial asthma. The trial was designed as a prospective double-blind parallel study of the effect of stepwise increase of either beclomethasone dipropionate or budesonide from 200 micrograms through 400 micrograms, to 800 micrograms daily in three consecutive periods of 4 weeks. At the end of each period, the adrenal stress response was evaluated by measurements of serum cortisol and androstenedione during a short adrenocorticotropic hormone test. The unstimulated diurnal production of glucocorticosteroids was assessed by measurements of free cortisol in 24-hour urine samples. Free cortisol in urine was found a valid measure of the total diurnal excretion of cortisol metabolites, since it exhibited a good correlation to the fractional cortisol metabolites measured by gas chromatography. The adrenal response to adrenocorticotropic hormone stimulation was unaffected by treatment or dose. The unstimulated diurnal production of glucocorticosteroids demonstrated a highly significant dose-related suppression in response to the inhaled steroids. No significant difference was found between the two topical steroids (probability value 5.3%), and yet the suppression was apparent in the group of children treated with beclomethasone dipropionate but not in the group of children treated with budesonide. Further studies are desirable in order to ascertain whether budesonide offers an improved ratio between beneficial anti-inflammatory effect and unwanted systemic activity.
Twenty healthy individuals (15 men and 5 women) with initial fasting serum triglycerides greater than or equal to 1.80 mmol/l and euglobulin clot lysis time after venous occlusion greater than or equal to 60 min (upper normal limit 45 min) were tested for fibrinolytic response to venous occlusion and intravenous injection of desmopressin (DDAVP), serum lipids, serum glucose and relative body weight before and after a minimum of 3 to a maximum of 12 months' diet intervention. In order to be defined as a good diet responder, at least 20% reduction of the initial serum triglyceride concentration was required. At the end of the study, half of the participants (7 men and 3 women) met the criteria of good diet responders. All of these showed an improved fibrinolytic response to DDAVP injection, and 7 out of 10 had a normalized fibrinolytic response to venous occlusion. We conclude that, through dietary measures with substantial reduction of hypertriglyceridaemia, it is possible to improve and even normalize the fibrinolytic potential.
Dendritic depolarization, which seems to be involved in the induction of long-term potentiation (LTP), was elicited by localized glutamate application. When paired to low frequency synaptic activation in the same area, the subsequent changes had features in common with LTP, expressed as an increased probability of firing and shorter spike latency. The EPSP was not significantly increased.
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Calcium-dependent binding of C-reactive protein (CRP) to Aspergillus fumigatus was determined by enzyme-linked immunosorbent assay. A homogenate of young hyphae was fractionated by hydrophobic interaction chromatography followed by gel filtration. High CRP-binding activity was found in a fraction of mol. wt c. 500,000 which was characterised by strong binding to the hydrophobic column. Three fractions of less conspicuous CRP-binding activity were identified (c. 500 000, 150 000 and 150 000-50 000 mol. wt respectively). In these four fractions, phosphorylcholine was detected by an anti-phosphorylcholine mouse hybridoma antibody. Some CRP-binding activity in fractions with low affinity for the hydrophobic column did not correspond closely with the presence of phosphorylcholine. It is suggested that C-reactive substance in A. fumigatus is heterogeneous. The C-reactive substances did not correspond with fractions containing major antigens (470 000 and 250 000 mol. wt respectively) which elicit a strong immune response in man.
Antibodies to Aspergillus umbrosus were investigated in 181 Danish farmers, 137 farmers' spouses and a control group of 104 male blood donors with no relation to farming. By enzyme-linked immunosorbent assay (ELISA) higher levels of IgG antibodies were found in farmers than in their spouses and in non-farming controls (P less than 0.0001). By double immunodiffusion precipitating antibodies occurred in 11 farmers, in none of farmers' spouses and in one control subject. Farmers and farmers' spouses who were non-smokers had higher IgG antibody levels than smokers in the same groups (P less than 0.04). Farmers more than 30 years of age had higher IgG antibody levels than younger farmers (P less than 0.04). Farmers rearing cattle tended to have higher IgG antibody levels than farmers without cattle. No correlation between antibody levels and respiratory symptoms or lung function parameters (FEV1 or FVC) could be demonstrated.
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A rapid immunoelectrophoretic assay was developed to detect antibodies to Aspergillus fumigatus catalase. The method's diagnostic sensitivity for pulmonary aspergillosis was 88% (72-97%, 95% confidence limits) in 33 patients presenting with either aspergilloma or Aspergillus lung infiltrate. The diagnostic specificity was 94% (90-97%) as judged from 191 patients with other infiltrative lung diseases, including infections and neoplasia. None of the 185 healthy subjects had catalase antibodies. The highest titres (ranging up to 256) were found in aspergillosis patients with cavitary lesions. Catalase antibody titres increased in two patients with concomitant development of lung cavities and mycetomas. In patients with resected or stable Aspergillus lung disorders catalase antibody titres declined by less than one dilution step per year.
The number of plaque-forming cells (PFC) developed in pokeweed mitogen (PWM)-activated unfractionated or T/B separated, 4:1 reconstituted cultures of peripheral blood lymphocytes (PBL) with well-characterized subpopulations obtained from healthy, aged subjects was compared to that of young blood donors. The absolute number of PBL in the aged was reduced by 36%, and the percentage of sheep erythrocyte-rosette-forming cells (E-RFC) by 27%, compared to the percentage obtained in young donors. The IgM-, IgG- and IgA-immunoglobulin (Ig) secretion was monitored with a protein A PFC assay. The number of PFC in PBL cultures of the aged was 58% of the number found in cultures of the young controls. The number of PFC generated in cultures of autologous irradiated T and untreated B cells showed a 104% increase in the aged whereas a 63% increase was obtained using cells from young individuals. Co-cultures of young B cells with untreated or irradiated young or aged T cells showed a significant rise in the PFC response in cultures with irradiated aged T cells, while an equal number of PFC was generated in cultures of young B cells with young or aged untreated T cells. Our results demonstrate a decreased number of PBL, especially T cells, an impaired B cell function and a pronounced enhancement of the PFC response in cultures of irradiated aged T cells and young or aged B cells, whereas the T helper function of untreated cells was found to be normal. The influence of monocytes on the PFC response did not differ in the two groups.
Antigens in ruptured mycelium of 18 Aspergillus strains including 14 clinical isolates of A. fumigatus were studied by immunoelectrophoresis. One antigenic component of molecular weight 470 000 previously characterized by hydrophobic interaction chromatography and gel filtration and a second component with catalase activity were detected in all A. fumigatus isolates but in varying quantities. The 470 000 antigen complex cross-reacted with antigens in A. flavus and A. nidulans but not in A. niger or A. terreus. A. fumigatus catalase antigen cross-reacted with catalase in A. flavus, A. nidulans and A. terreus, but not in A. niger. One A. fumigatus isolate produced two catalase antigens showing a reaction of partial identity. A. flavus also produced two catalase antigens, one of which was species-specific.
The frequency of Aspergillus fumigatus isolates from sputum was assessed prospectively during a 22-month period in 156 patients with cystic fibrosis (CF) from one center, and findings were compared to a cross-sectional evaluation of specific IgG and IgA antibodies, occurrence of chronic Pseudomonas aeruginosa infection, and pulmonary function. The prevalence rate for the 22-month period was 40%. Positive A. fumigatus cultures appeared to be independent of the presence or duration of chronic bronchopulmonary Ps. aeruginosa infection, but isolation of A. fumigatus in patients with pseudomonas infection for more than 5 years was associated with notably decreased pulmonary function. Levels of IgG antibodies to a 470,000 daltons A. fumigatus antigen fraction were higher in patients with positive cultures in the observation period than in those without. IgG antibodies to a 25,000-50,000 daltons antigen fraction were directly correlated to A. fumigatus frequency in patients with positive cultures both prior to and during the survey. On the other hand, levels of IgA antibodies to the 470,000 daltons fraction were inversely related to A. fumigatus frequency, suggesting a role of IgA antibodies in the bronchial clearance of aspergilli. Decreased pulmonary function was found to be associated with elevated levels of A. fumigatus antibodies. It is concluded that immune reactions elicited by A. fumigatus may play a role in clearance of the fungus from the airways but also may contribute to lung morbidity in some patients.