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Biomedical subjects

R Dahl

Publications and source records attributed to R Dahl.

At least 235 records · Page 13Linked to original sources

Somatostatin receptors are biologically active before they are inserted into the plasma membrane.

We have examined the biological activity of intracellular somatostatin (SRIF) receptors in cultured rat anterior pituitary cells. We used digitonin-permeabilized cells to introduce free SRIF intracellularly and chloroquine-treated cells to promote intracellular accumulation of SRIF via a receptor-mediated pathway. At a concentration of 0.001%, digitonin (3-min incubation at 37 C) allowed [125I]SRIF to enter the cells without affecting cell viability. Autoradiography of [125I]SRIF demonstrated its association with secretion vesicles (28%), nuclei (25%), and other intracellular organelles. An acid wash technique that removes cell surface-bound ligand revealed that both digitonin-permeabilized cells and chloroquine-treated cells accumulated approximately twice as much intracellular SRIF as did control cells. The biological activities of intracellular SRIF accumulated via two different pathways, receptor mediated and through digitonin-produced pores in the plasma membrane, were different. In chloroquine-treated cells, the accumulation of intracellular SRIF did not result in its additional biological effect. SRIF inhibited GH-releasing factor-induced GH release from 578 +/- 12 to 168 +/- 9 ng/10(6) cells X 30 min, which did not differ from the control value. Cells incubated with digitonin demonstrated normal basal (160 +/- 9 ng/10(6) cells X 30 min) and GH-releasing factor-stimulated GH release (564 +/- 11 ng/10(6) cells X 30 min). However, the inhibitory action of SRIF in these cells was approximately 30% greater (98 +/- 8 ng/10(6) cells X 30 min) than that in either control or chloroquine-treated cells, suggesting that SRIF freely admitted intracellularly produces additional biological activity. These observations confirm the presence of the intracellular receptors and suggest that these receptors exist in a biologically active form.

Animals↗

The effect of RU 41.740, an immune modulating compound, in the prevention of acute exacerbations in patients with chronic bronchitis.

The effect of Biostim (RU 41.740), a new non-specific immune modulator, in reducing the number of acute exacerbations in patients with chronic bronchitis, was examined. One hundred and ninety-eight patients with chronic bronchitis stages 2 and 3 entered the study, which was conducted as a multicenter, double-blind, parallel three-group, placebo-controlled trial. The patients were randomised to placebo, Biostim 2 or 8 mg per day, and received treatment for 1 week every other week for 3 successive months during the winter 1983. A significant (p = 0.005) reduction in the number of acute exacerbations was observed in the patients treated with Biostim 2 mg/day, whereas no effect was observed in the placebo or 8 mg/day group. No serious side-effects were encountered.

Acute Disease↗

Procaterol and terbutaline in bronchial asthma. A double-blind, placebo-controlled, cross-over study.

Procaterol, a new beta-2 adrenoceptor stimulant, was studied in a double-blind, placebo-controlled, cross-over trial in patients with bronchial asthma. Oral procaterol 50 micrograms b.d., procaterol 100 micrograms b.d., and terbutaline 5 mg t.i.d., were compared when given randomly in 1-week treatment periods. The best clinical effect was found with terbutaline. Both anti-asthmatic and tremorgenic effects of procaterol were dose-related. Procaterol appeared effective in the doses tested, and a twice daily regimen would appear to be suitable with this drug.

Adolescent↗

Internalization and cellular processing of somatostatin in primary culture of rat anterior pituitary cells.

Somatostatin (SRIF) binding, internalization, and intracellular processing in primary culture of anterior pituitary cells have been studied using somatostatin coupled to an electron-opaque marker, colloidal gold. Initially, after 2 min of incubation (37 C), gold-conjugated SRIF is localized on the cell surface, with 38% of the marker being found around microvilli, 10% at the junction of secretion vesicles with the plasma membrane, and 51% distributed over the remaining areas of the cell membrane. There was no internalization of SRIF at this time. After 20 min of incubation, distribution of the cell-surface bound hormone was similar to that at 2 min (40.6% at microvilli, 12% at the junction with the secretion vesicle, and 47.4% over the rest of the plasma membrane). However, 12% of the electron-opaque markers were found intracellularly in association with coated vesicles, intermediate-sized vesicles, lysosomes, and Golgi structures. SRIF did not enter pituitary cells at 4 C. To study the role of coated vesicles in internalization of SRIF, we have measured somatostatin binding to isolated coated vesicles before and after various treatments and sonication. SRIF binding to sonicated vesicles (3.46 +/- 0.36 fmol/micrograms protein), was much greater than to intact ones (0.75 +/- 0.16 fmol/micrograms protein), suggesting intraluminal localization of SRIF receptors in the coated vesicles. Approximately 80% of SRIF-binding sites were recovered on the intraluminal surface of the coated vesicles. The results of these experiments suggest that internalization of SRIF is a time- and temperature-dependent process. Within the cell, SRIF is routed to either lysosomes or the Golgi apparatus. Coated vesicles participate in intracellular translocation of SRIF-receptor complexes. It appears that the receptor for SRIF being internalized is located on the intraluminal surface of the coated vesicle.

Animals↗

Eosinophils and cellular injury: the Gordon phenomenon as a model.

Three eosinophil proteins, eosinophil cationic protein (ECP), eosinophil protein-X (EPX), and eosinophil-derived neurotoxin (EDN), have neurotoxic properties. EDN and EPX may be identical. ECP is by far the most potent neurotoxic eosinophil-derived protein. The damaging effect of the three proteins have been claimed to be selective. This selectivity can, at least in part, be explained by way of the experimental injections. Several observations are in favour of a selectivity through accumulation. Immunocytochemical localization of intraventricular injected ECP supports this hypothesis and indicates furthermore that ECP has an immediate reactivity towards and possible toxic effect against nervous tissue in general.

Animals↗

Localization of somatostatin receptors in secretion vesicles in anterior pituitary cells and pancreatic islets.

Secretion vesicles in anterior pituitary cells and pancreatic islets appear to translocate somatostatin receptors from the cell interior to the plasma membrane. In this study we attempted to localize somatostatin receptors on either the cytoplasmic or the intraluminal surface of the secretion vesicles. 125I-somatostatin binding was determined in intact secretion vesicles and vesicles disrupted either by sonication or solubilization. The binding of 125I-somatostatin was identical in intact and disrupted vesicles, indicating cytoplasmic orientation of somatostatin receptors. Pronase treatment of intact secretion vesicles removed approximately 90% of specific somatostatin binding. Sonication of pronase treated secretion vesicles did not reveal latent somatostatin binding sites. Gold-conjugated somatostatin binds to isolated secretion vesicles confirming the presence of somatostatin binding sites on the outer surface of these vesicles. We conclude that somatostatin binding sites are located on the cytoplasmic surface of secretion vesicles isolated from anterior pituitary cells and pancreatic islets.

Animals↗

Sensitivity to house dust mite and grass pollen in adults. Influence of the month of birth.

A comparison was made between the birth month of a control population and a sample of 240 adult patients with bronchial asthma or rhinitis and positive skin test towards house dust mite (Dermatophagoides pteronyssinus). The patients were born more frequently (P less than 0.005) in the summer and autumn months than in the other seasons. A similar comparison of 336 allergic patients with a positive skin test towards grass pollen (Phleum pratense) but no consistent seasonal preference in the birth months was revealed. This was possibly explained by the age of the patient group studied. The increased incidence of house-dust mite allergy in patients born in the months of May to September inclusive when house dust mites are supposed to be most abundant corresponds to a relative risk of 1.44. It is important to diminish the exposure to house dust mites in early childhood because exposure to allergens may influence the development of allergic disease in later life.

Adult↗

Effects of inhaled budesonide alone and in combination with low-dose terbutaline in children with exercise-induced asthma.

The effect of aerosolized terbutaline in a dose of 32.5 micrograms and its placebo, administered in a double-blind fashion, was studied in 14 children with exercise-induced asthma (EIA) before and during a 4-wk treatment period with aerosolized steroid (budesonide, 400 micrograms/day). Effects were assessed from the changes in peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and forced expiratory flow (FEF25-75) before and after treadmill exercise challenge. Compared with placebo there was a significant improvement in pulmonary function after terbutaline. During budesonide therapy, pulmonary function improved further, but there was no enhancement of the response to terbutaline. Terbutaline alone, budesonide plus placebo, and budesonide plus terbutaline reduced the exercise-induced fall in FEV1 by 30, 51, and 84%, respectively. The effect of budesonide on EIA was delayed during the 4 wk of treatment as compared with the improvement in resting pulmonary function. The present results suggest that 1 to 4 wk of therapy with inhaled corticosteroids decreases the severity of EIA. Further, the combined effect of inhaled corticosteroid and beta-2 agonist on pulmonary function appears to be additive.

Adolescent↗

The Gordon phenomenon induced by the eosinophil cationic protein and eosinophil protein X.

Cerebellar Purkinje cell degeneration after intracerebral injection of eosinophil granulocytes or extracts thereof is known as the Gordon phenomenon. The reaction is said to be highly selective. An eosinophil-derived neurotoxin (EDN) has recently been reported to induce the Gordon phenomenon. However, we report here that two eosinophil-derived proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), may induce the Gordon phenomenon after intraventricular injection. The potency of ECP is far greater than that of EPX and the latter is possibly identical to EDN. The Fink-Heimer staining for degenerating nerve fibers and boutons, however, indicated that the selectivity of the Gordon phenomenon is not as specific as was previously thought, since this method revealed degeneration of all brain areas in proximity to the ventricular system.

Animals↗

Importance of duration of treatment with inhaled budesonide on the immediate and late bronchial reaction.

The influence on the immediate and late bronchial allergic reaction after pretreatment with budesonide was investigated in 10 asthmatic patients with dual bronchial responses to bronchial provocation tests. Pretreatment was given in daily doses of 1 mg inhaled budesonide from a pressurized aerosol. In the first study pretreatment was given for 12 h and one week and in the second study for one week and one month. The late allergic reaction decreased markedly after 12 h pretreatment but additional effect was obtained after extended pretreatment. The immediate allergic reaction decreased less after pretreatment for 12 h and one week than did the late allergic reaction. Pretreatment for one month decreased also the immediate reaction substantially.

Adult↗