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Biomedical subjects

B Lundgren

Publications and source records attributed to B Lundgren.

At least 127 records · Page 7Linked to original sources

Harvesting and subculturing cells growing on denatured-collagen coated microcarriers (Cytodex 3).

Selecting correct procedures and conditions for harvesting cells was essential for successful subcultivation of cells when using the microcarrier culture technique. The proteolytic enzymes trypsin, Dispase and collagenase were compared with respect to the yield and the viability of Vero cells when harvested from Cytodex 3 microcarriers. Treatment with Dispase or trypsin resulted in similar viabilities but recovery after trypsin treatment was improved. The advantage of using collagenase was the improved plating efficiency of cells when subculturing to new microcarrier cultures. Pre-washing the confluent microcarriers with EDTA (0.02% w/v) improved the yield and the viability when harvesting with trypsin or collagenase. The stage of the culture cycle when cells were harvested did not influence relative recovery or viability. In contrast, significant differences in recovery and viability were found when harvesting cells grown in the presence of different batches of foetal calf serum. The results confirm that the choice of enzyme for harvesting depends upon the cell type and purpose of the culture.

Animals↗

Characterization of the beta-adrenergic inhibition of motility in cat colon strips.

The inhibition of spontaneous contractile activity in isolated cat colon strips by isoprenaline, prenalterol and terbutaline was studied. Isoprenaline produced a concentration-dependent complete inhibition with an EC50 of 6.18 nM. Prenalterol and terbutaline produced a concentration-dependent partial inhibition of 68 and 75% respectively, with EC50 of 0.52 and 0.43 microM respectively. The inhibitory effects of the three agonists were blocked by metoprolol and IPS 339 in such a way as to suggest that the prenalterol effect was mediated by beta 1-adrenoceptors and the terbutaline effect was mediated by beta 2-adrenoceptors, whereas the effect of isoprenaline appeared to be mediated by both types of receptors. Thus, the results indicate that both beta 1- and beta 2-adrenoceptors are involved in the adrenergic inhibition of spontaneous contractile activity in the cat colon strip. Qualitative effects of prenalterol and terbutaline on the spontaneous contractile activity in the cat colon strip indicated that the beta 1-adrenoceptor-mediated effects may be related to inhibition of the activity in cholinergic neurons, whereas the beta 2-adrenoceptors may be acting on the smooth muscle cells per se.

Adrenergic beta-Agonists↗

beta 1-and beta 2-adrenoceptor stimulatory effects of prenalterol.

Prenalterol, previously characterized as a functionally cardioselective partial beta-adrenoceptor agonist, was shown to relax K+ -elicited contractures in the uterine muscle from progesterone pretreated rats (pD2 7.7) and to increase beating rate in the rat right atrium (pD2 8.0) at about the same concentrations with maximal effects corresponding to 94 and 82% respectively of those of isoproterenol. Terbutaline, with equal maximal effects as isoproterenol, was 50 times more potent in the uterus (pD2 7.8) than in the right atrium (pD2 6.1). Both tissues displayed a high sensitivity to isoproterenol (pD2 9.1 in both tissues) indicating large receptor reserves for the full agonist. The maximal relaxing effect of prenalterol in the uterus was obtained at about a three-fold increase of the cyclic AMP content, which is similar to that obtained with isoproterenol at a corresponding relaxation. The effects in the uterine muscle of all three agonists were mediated through beta 2-adrenoceptors since beta 2-adrenoceptor blockers (ICI 118, 551 and IPS 339) antagonized the effects in concentrations which had only marginal effects on the atrial responses of the agonists. The beta 1-antagonists pafenolol and pamatolol in concentrations higher than those, which blocked the effects of the agonists on beating rate, were devoid of inhibitory effects in the uterus. These results indicate that prenalterol possesses the ability to elicit a functional response by stimulation of either beta 1-or beta 2-adrenoceptors provided that the tissue has a large spare receptor reserve for full agonists.

Adrenergic beta-Agonists↗

Cardiostimulatory effects of prenalterol, a beta-1 adrenoceptor partial agonist, in vivo and in vitro. Correlation between physiological effects and adenylate cyclase activity.

The cardiostimulatory effects of prenalterol, a beta-1-adrenoceptor partial agonist, were studied in vivo and in vitro and compared to those evoked by isoprenaline, a full agonist, and to those of other partial agonists. In the anaesthetized rat, prenalterol and terbutaline were found not to elevate the myocardial cyclic AMP content; this was in sharp contrast to isoprenaline. Both partial agonists did, however, produce significant effects on heart rate. In the anaesthetized cat, prenalterol exhibited chronotropic and inotropic intrinsic activities of 88 and 76% respectively in relation to isoprenaline. No statistically significant increase in myocardial cyclic AMP content could however be detected. Prenalterol did not stimulate adenylate cyclase significantly in the cat myocardial homogenate. This was also true of the beta-2-adrenoceptor selective partial agonist procaterol. In this preparation, isoprenaline, noradrenaline and adrenaline acted as full agonists. Furthermore, prenalterol produced a concentration-dependent inhibition of isoprenaline-activated adenylate cyclase. Our data indicate that maximal cardiac stimulation occurs at a low level of adenylate cyclase activation and low myocardial cyclic AMP concentration when provoked by a full beta-adrenoceptor agonist. The maximal physiological effects of a partial agonist such as prenalterol may consequently be achieved at a marginal activation of the adenylate cyclase. The present data may thus support the hypothesis of a large beta-adrenoceptor reserve for full agonists in the heart.

Adenylyl Cyclases↗

Urine microscopy as screening method for bacteriuria.

Fresh urine samples from 90 ambulatory patients with urological disorders were examined for leucocytes by counting the number of WBC/mm3 and per high power field (HPF) in sediment. Bacteria could be cultured in 20 samples, 18 of which contained greater than 8 WBC/mm3. Two (3%) of the 63 samples with less than or equal to 8 WBC/mm3 contained bacteria. Bacteriuria was found in two (3%) of 65 samples containing 0--1 WBC/HPF. Microscopic examination of the sediment might be used for the screening of patients with a high frequency and urgency of micturition for bacteriuria. A normal number of urinary leucocytes (less than or equal to 8/mm3) indicates that no bacteria will be found in culture. Leucocyturia indicates a high probability of bacteriuria.

Adult↗

Treatment of early localized breast cancer in elderly patients by Tamoxifen.

Twenty-seven early localized breast cancer cases in elderly patients, 21 stage I and six stage II, were treated with Tamoxifen only. In 15 cases there was complete radiological remission and in seven cases partial remission or growth arrest. Five cases did not respond to treatment. Tamoxifen seemed to be a useful alternative treatment for this group of patients. Possibly tumour mass and growth rate may affect the response to antioestrogen treatment.

Aged↗

Single oblique-view mammography for periodic screening for breast cancer in women.

A population, originally 6,845 women, 40 years of age and over, was screened for breast cancer by single oblique-view mammography in 1974, 1977, and 1980. Of the 5,789 women remaining in their parish in 1980, 94% had attended the screening at least once. Of 111 breast cancers diagnosed in the 6.25-year study period, 78% were detected at screening, 15% as interval cancers, and 7% among nonresponders. Sixty-three percent of the women had tumors in clinical stage I, and 59% had tumors less than or equal to 10 mm. The predictive value for biopsy recommendations by mammography was 79%. This method was considered very suitable for screening. In the older age groups there was probably some overdiagnosis of cancers that would never have become symptomatic.

Adult↗

Alternative surfaces for microcarrier culture of animal cells.

As part of an effort to broaden the applicability and efficiency of microcarrier cell culture various alternative new microcarriers were synthesized. The microcarriers were compared as substrates for the growth of several types of cells and with respect to binding of proteins from the culture medium. Cross-linked dextran has been found to be the most suitable material for a microcarrier matrix and was used as the matrix for the new microcarriers. One type of microcarrier was synthesized so that the charges necessary for cell attachment were present only in the surface layer of the microcarrier in the form of N,N,N-trimethyl-2-hydroxyaminopropyl groups. The resulting microcarriers had a very low capacity to bind proteins from the culture medium (e.g. albumin and IgG) and such proteins could be removed from the cultures more efficiently than when using previous microcarriers. A new principle was used for the development of the other type of microcarrier. A surface layer of cross-linked denatured collagen provided the surface for growth of cells. These microcarriers provided a "natural" substrate for cell growth and allowed improved attachment and spreading of cells with epithelial morphology. Harvesting cells from these microcarriers with proteolytic enzymes was more efficient than with previous microcarriers. The two alternative microcarriers should result in improved process efficiency and have a potential value in the preparation of live vaccines.

Animals↗

Sustained cardiac beta adrenoceptor blockade in vitro and increased vulnerability to aconitine-induced arrhythmias in vivo after propranolol withdrawal in rats.

The present study was undertaken in order to investigate the possibility of cardiac hypersensitivity to norepinephrine (NE) after propranolol withdrawal in rats. The effect of NE was studied on heart rate and left intraventricular pressure development (maximal dP/dt) in the isolated perfused heart at various time periods after termination of the propranolol feeding. Also, the influence of propranolol withdrawal on vulnerability to aconitine-induced arrhythmias in vivo was evaluated in anesthetized rats. No hypersensitivity to NE was seen in the perfused rat heart 1 and 3 days after propranolol withdrawal. Rather, a depressed response to NE was registered suggesting a long half-life for the disappearance of beta adrenoceptor blockade. Increased vulnerability to aconitine-induced arrhythmias was observed 1 and 3 days after treatment with propranolol had ceased. Rats receiving propranolol continuously until experimentation exhibited an elevated threshold to aconitine-induced arrhythmias. These data indicate that a hypothetical rebound phenomenon after withdrawal of propranolol is not associated with an increase in mechanical performance of the heart in response to NE. A decreased threshold for development of arrhythmias appears, however, to be at hand, perhaps due to an inbalance in the transmembrane sodium flux in the heart in the early time course after propranolol withdrawal.

Aconitine↗

Breast cancer screening in Sweden. The single modality approach.

Four population-based breast cancer screening projects are in progress in Sweden, three of which are randomized studies. Mammography is the only screening method. 51% of all carcinomas detected at the first screening were either in situ or invasive with a diameter of 10 mm or less. Axillary metastases were found in 16% of the patients. Sensitivity was over 90% in all projects. The ultimate aim of the randomized projects is to demonstrate the effect of screening on breast cancer mortality. It is estimated that mortality statistics will reach significant levels in 1983.,

Adult↗

Beta-adrenoceptor blockade by atenolol, metoprolol and propranolol in the anaesthetized cat.

The inhibitory effects of atenolol, metoprolol and propranolol on isoprenaline-induced tachycardia, broncho-relaxation and vasodilatation were investigated in the reserpinized and anaesthetized cat. In low doses all three antagonists inhibited the heart rate response to isoprenaline, the order of potency being propranolol greater than metoprolol greater than atenolol. While propranolol inhibited the bronchodilation and vasodilation responses to isoprenaline in the same dose range as it blocked the heart rate response, atenolol and metoprolol had to be given in considerably higher doses to block these effects. The results indicate that both metoprolol and atenolol, in contrast to propranolol, are selective beta1-adrenoceptor antagonist. No statistically significant difference in the degree of selectivity was found between metoprolol and atenolol. The three compounds were devoid of intrinsic beta-mimetic activity.

Adrenergic beta-Antagonists↗

Single-view mammography screening. Three-year follow-up of interval cancer cases.

In 1974, screening trials indicated that both the sensitivity and specificity of single-view mammography are high. During the subsequent three years, 11 cases of breast carcinoma have been detected in the study population of 6,845 women aged 40 or older. The average incidence was three cases per year, compared to the expected rate of 8.9. The age-adjusted incidence rate in 1975, the year after screening, was 55.4 per 100,000, which is 40% of the expected rate of 140. In 1976 it was 75.9, or 54% of the expected rate of 141. These results support the view that single-view mammography is an efficient screening method, at least in the subject population described.

Adult↗