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Biomedical subjects

B Larsson

Publications and source records attributed to B Larsson.

At least 343 records · Page 19Linked to original sources

Immunological comparison between human and rat plasminogen activators in blood and the vessel wall.

To evaluate the rat as an experimental model for plasminogen activator research, the ability of antibodies specific for human tissue type plasminogen activator and urokinase to suppress the plasminogen activator activity in whole plasma and in the vessel wall was studied in both rat and man. Plasminogen activator activity in plasma was assayed on fibrin plates containing plasminogen. Plasminogen activator in the vessel wall was shown by the fibrin side technique. Antibodies against human tissue type melanoma cell activator and urokinase were raised in goats and mixed into the fibrin film or the fibrin plates. In both species antibodies to melanoma cell activator were able to suppress the plasminogen activator activity completely in plasma and in the vessel wall. Anti-urokinase, however, had no suppressing effect. In rat plasma the inhibitory effect on the fibrinolytic activity was seen only with high concentrations of antibodies against melanoma cell activator, which suggests that rat plasminogen activator in plasma and vessel walls is similar to, but not identical with, human tissue type plasminogen activator.

Animals↗

Local anaesthetics and tinnitus. Proposed peripheral mechanism of action of lidocaine.

To elucidate the question whether lidocaine reduces tinnitus by a central or by a peripheral mechanism of action, its effect on tinnitus was compared with that of QX-572, a quaternary ammonium derivative of lidocaine which does not readily penetrate the blood-brain barrier. The results of experimental as well as clinical investigations indicate that the effects of lidocaine and QX-572 on tinnitus are mediated by a peripheral mechanism possibly related to their accumulation on inner ear melanin.

Animals↗

Tocainide and tinnitus. Clinical effect and site of action.

Tocainide, an amine analogue of lidocaine, which can be taken orally, was tested on 9 patients with severe tinnitus. 6 patients responded to the drug. In 4 patients the effect ceased after about 2 weeks despite continuous medication. 2 patients are still on this medication after more than 2 years. The binding of tocainide to melanin was analysed in vitro and in vivo in rats. It was concluded that the effect of tocainide on tinnitus is mediated by a peripheral mechanism possibly related to the accumulation on inner ear melanin.

Animals↗

Dilatation of the cervix by oral PGE2 before first-trimester termination of pregnancy.

Twenty-four patients--all primigravidae with an especially narrow, rigid cervix--were given PGE2 tablets or placebo tablets in order to prime the cervix before first trimester termination of pregnancy. 1.5 mg PGE2 or placebo tablets were administered hourly for 12 hours on the day before vacuum aspiration. The diameter of the cervix was measured by means of a Hegar dilator prior to administering the tablets and also before the vacuum aspiration the following day. The plasma level of 15-keto-13,14-dihydro-PGF2 alpha was determined before the treatment and again before the vacuum aspiration. All the 12 patients treated with PGE2 tablets had an average change in cervix diameter of 2 mm, whereas in the placebo group the average change was 0.58 mm.

Abortion, Induced↗

Effects of estradiol on norepinephrine-induced contraction, alpha adrenoceptor number and norepinephrine content in the female rabbit urethra.

Several studies have revealed that estrogen treatment increases the reactivity to catecholamines of various tissues. In the present study it was found that estrogen treatment caused an increased sensitivity to norepinephrine (NE) of the isolated female rabbit urethra. There was a 3-fold shift to the left of the concentration-response curve for longitudinal tension in perfused urethras and for tension in urethral ring preparations. Possible mechanisms for this increase in sensitivity were investigated by studying radioligand binding to the alpha adrenoceptors and by measuring the NE content of the urethras. Using [3H]dihydro-alpha-ergocryptine as a marker for alpha adrenoceptors, a more than 2-fold increase in the receptor number was found after estrogen treatment. This is suggested to be attributable to a selective increase in the number of alpha-2 adrenoceptors. No significant change was found in the affinity of [3H]dihydro-alpha-ergocryptine to the receptor. The total NE content in the urethra was not changed by estrogen treatment. However, if calculated per milligram of wet weight, the NE content was reduced to half in estrogen treated animals. It is suggested that in the rabbit urethra the estrogen-induced increased sensitivity to the contractant effects of NE, at least in part, is attributable to an increase in the number of postjunctional alpha-2 adrenoceptors.

Animals↗

The relative biological effectiveness in V79 Chinese hamster cells of the neutron capture reactions in boron and nitrogen.

V79 Chinese hamster cells were irradiated in the presence of different amounts of boric acid with thermal neutrons at the Medical Research Reactor at Brookhaven National Laboratory. From the linear dose-survival curves observed, a D0 value of 66 rad for the 10B(n, alpha) 7Li neutron capture reaction was obtained. No dependence of this value on the concentration of boric acid was found. Comparing this value to the D0 value of 150 rad obtained with 250 kVp X rays between 10 and 0.01% survival, an extrapolated RBE value of 2.3 was calculated. By irradiation of the same line of cells with cold neutrons at the Institut Laue - Langevin , a D0 value for the 14N(n,p)14C reaction of 77 rad was obtained, with a corresponding RBE value of 1.9. Comparison is made with previously published RBE values for the 10B(n, alpha) 7Li reaction.

Animals↗

Hydrolysis of chylomicron retinyl esters by an acid hydrolase of rat liver.

Rat liver homogenate hydrolyzed chylomicron remnant retinyl esters with pH optima 4.5, 6 and 8. The retinyl ester hydrolysis at pH 4.5 was correlated to the acid phosphatase activity in different subcellular fractions, and thus the highest activity was found in highly purified lysosomes. These fractions could also catalyze the reverse reaction, i.e., the esterification of retinol when incubated with excess palmitic acid. Purified rat liver lysosomes hydrolyzed chylomicron retinyl and cholesteryl esters with comparable rates, both being much lower than the hydrolysis of chylomicron triacylglycerols.

Animals↗

Why is the incidence of ischaemic heart disease in Sweden increasing?: study of men born in 1913 and 1923.

The mortality from ischaemic heart disease (IHD) in the USA is falling, and this has been attributed to a changing life-style, with less smoking, more jogging, and less fat consumption, and to improved medical care. Similar changes in life-style are taking place in Sweden, but IHD mortality there is increasing. The rising incidence of IHD was also evident in two cohorts of 50-year-old Swedish men examined 10 years apart. Despite similar levels of traditional IHD risk factors, the incidence of IHD in the second cohort was almost double that in the first. Possible explanations for the increasing IHD mortality are an increasing prevalence of obesity in Swedish men, a longer "incubation" time during which the traditional risk factors have acted in the second cohort, or the appearance of unknown risk factors.

Aged↗

Autoradiography in mice of tritiated 2-(2-furyl)benzimidazole and melanin-binding in vitro.

The distribution of tritiated 2-(2-furyl)benzimidazole ([3H]FB) in male and pregnant albino mice and male pigmented mice was studied by whole-body autoradiography. The most notable finding was the accumulation of radioactivity in the melanin-containing tissues of the eye, the inner ear and the hair follicles. An additional study in vitro on isolated bovine-eye melanin showed a substantial binding of [3H]FB to the melanin. The general distribution was characterized by a rapid excretion pattern, except for uptake in the thyroid and nasal mucosa. Transfer to fetuses was significant and the fetal distribution was dominated by excretion.

Animals↗

Evaluation of the effect of oxfendazole on sperm production and semen quality in boars.

Twice the recommended dose of oxfendazole was given as a single dose to each of 6 boars. From these and 6 placebo treated boars of similar age semen was regularly collected both before and after the antihelminth treatment. Sperm production (volume and total number of spermatozoa) and semen quality (motility and morphology of spermatozoa) were examined in each ejaculate. From these measurements and post-mortem examination of the genital organs there was no apparent negative influence of treatment on sperm production or semen quality.

Animals↗

Calcium antagonists: effects on cerebral blood flow and blood-brain barrier permeability in the rat.

1 Because they affect isolated cerebral arteries, some calcium antagonists have been studied on the intact cerebral circulation of the rat.2 Global cerebral blood flow ((133)Xe clearance technique) was measured in anaesthetized rats. Neither perhexiline (0.1 mug/kg to 1.0 mg/kg, i.v.) nor diltiazem (0.06-0.6 mg/kg, i.v.) had any significant effect on resting cerebral blood flow when measured 5 min after each dose. A high dose of nifedipine (1.0 mg/kg, i.v.) was administered during induced hypocapnia. Nifedipine failed to modify the hypocapnic vasoconstriction of the cerebral vasculature when compared to vehicle-treated rats.3 The possibility of discrete changes in regional cerebral blood flow was investigated. Local cerebral blood flow was measured in a number of brain regions by the [(14)C]-ethanol technique 15 min after the administration of nifedipine (20 or 100 mug/kg, i.v.). Nifedipine had no apparent effect on regional blood flow in the rat brain.4 Acute arterial hypertension increases protein leakage into the brain, a phenomenon susceptible to drugs that act on endothelial pinocytosis which is known to be calcium-dependent. The increase in protein extravasation, induced by the intravenous administration of either angiotensin II or adrenaline, was unchanged in rats previously treated with either nimodipine (20 mug/kg, i.v.) or nifedipine (50 mug/kg, i.v.) when dissolved in ethanol alone. However, nifedipine (20 mug/kg, i.v.) when dissolved in a solution of polyethylene glycol and ethanol further enhanced the hypertension-induced increase in brain albumin permeability.5 In conclusion, we have been unable to demonstrate any apparent effects of various calcium antagonists on the intact cerebral circulation of the rat, despite the number of different experimental models used.

Animals↗

Demonstration of alpha-adrenoceptors in the rabbit bladder base and urethra with 3H-dihydroergocryptine ligand binding.

The purpose of this work was to demonstrate the presence of alpha-adrenoceptors in a crude membrane preparation made from rabbit bladder base and urethra. This was achieved by radioligand binding studies, using 3H-dihydro-alpha-ergocryptine (3H-DHE) as the radioligand. The specific binding, i.e. the binding that could be inhibited by 10(-5) M phentolamine, was saturable with 73 fmol 3H-DHE bound per mg membrane protein. Binding was at steady state after 60 min., and reversible. Rate constants for association and dissociation were 3 X 10(7) M-1 min.-1, and 2 X 10(-2) min.-1, respectively. A number of compounds were tested for their abilities to compete with 3H-DHE for the binding sites. The relative affinity of some adrenoceptor agonists was: (-)-adrenaline greater than (-)-noradrenaline much greater than (+/-)-isoprenaline. Stereoselectivity was shown, since (-)-noradrenaline had 42 times higher affinity than (+)-noradrenaline. Adrenoceptor antagonists inhibited 3H-DHE binding in the following order of potency: DHE greater than phentolamine much greater than (+/-)-propranolol. The dissociation constant, KD, for DHE to the binding sites was estimated in three different ways. The constants were derived from saturation, competition, and kinetic studies, and gave KD values of 1.1, 1.4 and 0.7 nM, respectively. The results suggest that alpha-adrenoceptors were labelled by 3H-DHE in the tissue homogenates.

Animals↗

Thioamides as false melanin precursors: studies in murine melanomas.

Melanotic melanomas show a high rate of melanin synthesis. Foreign substances that are accepted as precursors in the formation of melanin may therefore be useful in the diagnosis and therapy of malignant melanotic melanomas, if labelled with suitable radionuclides. We have earlier reported that 2-thiouracil is incorporated in melanotic melanomas, apparently as a false melanin precursor. In the present study it is shown that methimazole and 5-iodo-2-thiouracil are as well accepted as melanin precursors. 5-Iodo-2-thiouracil is of special interest, since iodine has many clinically useful radioisotopes. The chemical properties that characterize substances which are incorporated as false precursors into melanin are discussed. A free sulfur ligand of the thioamides (2-thiouracil, 5-iodo-2-thiouracil, methimazole and thiourea are all incorporated into melanin) seems to be essential and the link between these substances and the melanin. Uracil (which lacks sulfur) and 2-benzylthiouracil (where the sulfur is blocked with a benzyl group) do not attach to melanin. Our conclusion therefore is that the thioureylene structure is the smallest common molecular fragment of the false melanin precursors.

Amides↗

Autoradiographic studies with albumin-bound 1-14C-linoleic acid in normal and essential fatty acid-deficient rats. A pilot study.

Young rats fed a diet providing 0.3, 3 or 10% of the energy as essential fatty acids (EFA) were given a single intravenous dose of albumin-bound 1-14C-linoleic acid. 1 animal from each group was killed at 1 and 18 h, respectively, after the injection and submitted to whole-body autoradiography. In general, the activities in the tissues were higher in the 0.3% group than in the other groups, whereas the differences between the 3% and the 10% group were small. In all groups the highest activity occurred in the brown fat. High activities were also noted in the liver, the adrenal cortex, the diaphragm, and the gastric and intestinal mucosa. The higher activities in the tissues of the rats fed 0.3% than in the tissues of those fed 3% or 10% EFA probably reflect a higher incorporation of fatty acids of the linoleic acid series into structural and other lipids in the former group due to the lack of EFA.

Adipose Tissue, Brown↗

Fibrinolytic activity in the walls of foot veins in women using combined contraceptive pills.

In the present study, the fibrinolytic activity of dorsal foot veins (FAV) was histochemically determined in 46 young and middle-aged healthy women, 26 of whom were using combined contraceptive pills (CCP). Significantly reduced FAV was demonstrated in women with a history of previous thrombophlebitis or family manifestation of deep venous thrombosis irrespective of age, as well as in middle-aged women using CCP, whereas the FAV of young women was uninfluenced by CCP and smoking. The FAV of the smoking middle-aged pill users was significantly reduced as compared to that of the young smoking pill users. With reference to this significant reduction of FAV it might be concluded that the combined contraceptive pill is unsuitable for middle-aged female smokers.

Adolescent↗

Priming and induction of labor with oral PGE2 in patients with low Bishop score.

Oral prostaglandin in hourly doses of 0.5 mg PGE2 was given to 58 patients with an initial Bishop score of five or less, for two 12-hour periods in order to prime the cervix. After priming, the patients were induced with oral PGE2; 90% of these patients were delivered. In a control group comprising 59 patients induced with oxytocin, the delivery rate was only 51%.

Administration, Oral↗

Irradiation effects upon ischemic regenerating rat liver cells.

Starch particles injected into the arterial and portal systems of the liver of the rat caused a temporary blockage of the liver circulation and consequent hypoxia in the liver cells. In the regenerating liver this resulted in a 30-40% decrease of thymidine incorporation into DNA, when analysed 1.5 hours after injection. Irradiation-induced cell damage, evaluated by thymidine incorporation 1.5 hours after irradiation with a single dose of X-rays, was not ameliorated by the ischemic condition. It is suggested that this depends on an inhibited nucleotide metabolism and DNA synthesis leading to an additive metabolic hypoxic effect of the starch particles on radiation damage. An equal level of thymidine incorporation, however, was found in an ischemic and a non-ischemic group of animals 16 hours after irradiation. In this case the liver cells in the ischemic group had overcome the additional inhibition of DNA synthesis caused by temporary hypoxia.

Animals↗