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Biomedical subjects

B Astedt

Publications and source records attributed to B Astedt.

At least 55 records · Page 3Linked to original sources
PubMed1989

The effect of cervical dilatation by laminaria tent in first trimester legal abortions on blood loss related to fibrinolytic activity in the decidua and placenta.

Increased blood loss (BL) has been reported after cervical dilatation by laminaria tent in legal abortions. The BL was measured in 72 women in whom first trimester legal vacuum aspiration was performed. The cervical canal was dilatated by laminaria tent in 37 patients, and mechanically with Hegar dilators in 35 patients. BL was studied in relation to the plasminogen activators (u-PA, t-PA) and the plasminogen activator inhibitors (PAI-1, PAI-2) in the decidua and placenta. There was no significant difference in BL between the two groups. Decidual PAI-1 concentrations were significantly higher in the laminaria tent group than in the Hegar dilator group. An inactivation of u-PA by PAI-1 might explain the lack of increase in BL among the laminaria tent group.

Abortion, Induced↗
PubMed1989

Repeated cranial computed tomographic and magnetic resonance imaging scans in two cases of eclampsia.

In two cases of eclampsia with consumptive thrombocytopenia, the maximum increase in blood pressure and the lowest platelet count coincided with the maximum degree of neurologic and neuroradiologic abnormality. Computed tomograms showed decreased attenuation, and T2-weighted magnetic resonance images showed increased signal intensity focally in the cerebral cortex and the deep gray and white matter. Blood pressure, platelet count, clinical status, and roentgenograms normalized completely in both cases. Severe arterial hypertension and disseminated transitory microvascular occlusions presumably caused multiple small foci of brain edema that resolved without remaining detectable ischemic brain damage.

Adult↗
PubMed1988

Kinetics of inhibition of tissue-type and urokinase-type plasminogen activator by plasminogen-activator inhibitor type 1 and type 2.

Highly purified plasminogen-activator inhibitors of type 1 (PAI-1) and type 2 (PAI-2), low-Mr form, were compared with respect to their kinetics of inhibition of tissue-type (t-PA) and urokinase-type plasminogen activator (u-PA). The time course of inhibition of plasminogen activator was studied under second-order or pseudo-first-order conditions. Residual enzyme activity was measured by the initial rate of hydrolysis of a chromogenic t-PA or u-PA substrate or by an immunosorbent assay for t-PA activity. PAI-1 rapidly reacted with single-chain t-PA as well as with two-chain forms of t-PA and u-PA. The second-order rate constant k for inhibition of single-chain t-PA (5.5 x 10(6) M-1 s-1) was about three times lower than k for inhibition of the two-chain activators. PAI-2 reacted slowly with single-chain t-PA, k = 4.6 x 10(3) M-1 s-1. The association rate was 26 times higher with two-chain t-PA and 435 times higher with two-chain u-PA. The k values for inhibition of single-chain t-PA, two-chain t-PA and two-chain u-PA were respectively, 1200, 150 and 8.5 times higher with PAI-1 than with PAI-2. The removal of the epidermal growth factor domain and the kringle domain from two-chain u-PA did not affect the kinetics of inhibition of the enzyme, suggesting that the C-terminal proteinase part of u-PA (B chain) is responsible for both the primary and the secondary interactions with PAI-1 and PAI-2. The k values for inhibition of single-chain t-PA and endogenous t-PA in plasma by PAI-1 or PAI-2 were identical indicating that t-PA in blood consists mainly in its single-chain form.

Glycoproteins↗
PubMed1988

Epidermal plasminogen activator inhibitor (PAI) is immunologically identical to placental-type PAI-2.

Plasminogen activator inhibitor (PAI) purified from human epidermis [(1986) FEBS Lett. 408, 273-277] was immunologically identified as placental-type PAI-2. In both fibrinolytic and synthetic substrate assays inhibitory activity of epidermal PAI was neutralized by anti-PAI-2, but not by anti-endothelial type PAI-1. Immunoblotting technique confirmed that the purified epidermal PAI is reactive with anti-PAI-2, but not with anti-PAI-1. Consequently PAI in human epidermis was demonstrable by immunohistochemical technique.

Antibodies, Monoclonal↗
PubMed1988

Determination of intermediates, products and cleavage site in the reaction between plasminogen activator inhibitor type-2 and urokinases.

Several specific inhibitors for plasminogen activators have been isolated from various organs and cell lines, those from human placenta and the human monocyte-like cell line U-937 being virtually identical. The reaction between this type of inhibitor, designated as type-2, and high-Mr and low-Mr urokinase-type plasminogen activators was followed by reversed-phase high-performance liquid chromatography and gel electrophoresis. The components, their stable complexes and their dissociation and cleavage products could be clearly identified in both systems. The amino acid sequence of the inhibitor at the cleavage site was determined to be -Met-Thr-Gly-Arg decreases Thr-Gly-His-Gly-. A 35-residue carboxy-terminal fragment was found to be released.

Amino Acid Sequence↗
PubMed1988

Progestogen regulation of tissue plasminogen activator in a human melanoma cell line.

The influence of progestogens, i.e. medroxyprogesterone, levonorgestrel and norethisterone, was studied in a melanoma cell line producing tissue-type plasminogen activator (t-PA). The cell cultures were exposed to the three progestogens by addition of the steroids dissolved in a weak alcoholic solution to the culture media, in which the released t-PA was assayed by an immunoradiometric method. Ethanol (0.76% w/v) stimulated the t-PA production, while significant inhibitory effect of the present progestogens in the concentration of 1.7 x 10(-6) M was recorded. By tenfold decrease in progestogen concentration significant reduction of t-PA levels was still seen in the cultures exposed to levonorgestrel, while medroxyprogesterone and norethisterone in this dose had no effect on t-PA release. Norethisterone differed from the other two progestogens in having weak toxic effect on melanoma cells. It was concluded that the progestogens studied, in particular norethisterone and levonorgestrel, had an inhibitory effect on the production of t-PA in melanoma cell culture.

Ethanol↗
PubMed1988

Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release.

We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5-8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosuppressed with Cyclosporin A. The grafts produced an extensive new DA-containing terminal network in the previously denervated caudate-putamen, and they normalized amphetamine-induced, apomorphine-induced and spontaneous motor asymmetry in rats with unilateral lesions of the mesostriatal DA pathway. Grafts from an 11.5-week old donor exhibited a lower survival rate and smaller functional effects. As assessed with the intracerebral dialysis technique the grafted DA neurons were found to restore spontaneous DA release in the reinnervated host striatum to normal levels. The neurons responded with large increases in extracellular striatal DA levels after the intrastriatal administration of the DA-releasing agent d-amphetamine and the DA-reuptake blocker nomifensine, although not to the same extent as seen in striata with an intact mesostriatal DA system. DA fiber outgrowth from the grafts was dependent on the localization of the graft tissue. Thus, grafts located within the striatum gave rise to an extensive axonal network throughout the whole host striatum, whereas grafted DA neurons localized in the neocortex had their outgrowing fibers confined within the grafts themselves. In contrast to the good graft survival and behavioural effects obtained in immunosuppressed rats, there was no survival, or behavioural effects, of human DA neurons implanted in rats that did not receive immunosuppression. In addition, we found that all the graft recipients were immunized, having formed antibodies against antigens present on human T-cells. This supports the notion that the human neurons grafted to the non-immunosuppressed rats underwent immunological rejection. Based on an estimation of the survival rate and extent of fiber outgrowth from the grafted human fetal DA neurons, we suggest that DA neurons that can be obtained from one fetus may be sufficient to restore significant DA neurotransmission unilaterally, in one putamen, in an immunosuppressed PD patient.

Amphetamine↗
PubMed1988

Fibrinolysis during normal human pregnancy: complex inter-relationships between plasma levels of tissue plasminogen activator and inhibitors and the euglobulin clot lysis time.

Although it has been previously considered that blood fibrinolytic capacity is reduced during pregnancy, this has been disputed. Also the mechanisms underlying any change in fibrinolysis in pregnancy require clarification. We have therefore measured the plasma activity of tissue plasminogen activator (t-PA) and inhibitors (t-PAi) and the concentration of the pregnancy specific inhibitor (PA12) antigen, as well as the euglobulin clot lysis time (ECLT) during normal pregnancy. Plasma concentrations of fibrinogen, plasminogen, fibrin(ogen) degradation products (FDP) and cross-linked products (D-dimer) were also monitored. We confirm a marked reduction of the fibrinolytic activity of the plasma euglobulin fraction from the second trimester, and a parallel reduction in t-PA and increase in t-PAi activities, with rapid return to non-pregnant levels post-partum. In contrast, PAI2, whilst undetectable in non-pregnant control plasma, was already measurable in the first trimester, increased through pregnancy, and remained at a high concentration up to at least 48 h post-partum. Fibrinogen and plasminogen concentrations rose progressively through pregnancy and FDP and D-dimer were frequently detectable in late pregnancy plasma. Changes in the ECLT and plasma t-PA and t-PAi activities in pregnancy cannot therefore be directly related to the concentration of PAI2 antigen. Also, despite the apparent marked reduction in fibrinolytic capacity fibrin(ogen) breakdown products are frequently present in increased plasma concentrations in late pregnancy.

Female↗
PubMed1987

Tissue plasminogen activator and urokinase in normal, dysplastic and cancerous squamous epithelium of the uterine cervix.

The distribution of tissue plasminogen activator (t-PA) and urokinase (u-PA) was investigated immunohistochemically in squamous epithelium of the uterine cervix, in normal and dysplastic conditions as well as in preinvasive and invasive carcinomas. Normal epithelium showed presence of both t-PA and u-PA immunoreactivity only in the superficial cellular layer, whereas in preinvasive lesions they were present in all layers. In sections of normal specimens as well as preinvasive lesions the UK immunoreactivity was weaker compared to that of t-PA. Invasive lesions showed a patchy distribution of t-PA and u-PA immunoreactivity. Furthermore, it could be demonstrated that stromal cells close to the infiltrating malignant squamous epithelium contained t-PA immunoreactivity and also u-PA immunoreactivity. Further immunohistochemical studies disclosed that these cells were macrophages.

Cervix Uteri↗
PubMed1987

Plasminogen activator inhibitors from placenta and fibrosarcoma cells are antigenically different as evaluated with monoclonal and polyclonal antibodies.

Plasminogen activator inhibitor (PAI) purified from human placenta was compared to PAI purified from conditioned cell culture fluid of the human fibrosarcoma cell line HT-1080. The two inhibitors had a similar mobility (Mr approximately 50,000) in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Purified placental inhibitor revealed 2 major and 1 minor Coomassie blue stainable bands, while the fibrosarcoma inhibitor appeared as one band. By immunoblotting analysis both monoclonal and polyclonal antibodies against each of the inhibitors showed reaction with the inhibitor against which they were raised, but not cross reaction with the other inhibitor. Similar results were obtained, when antibody binding was tested by ELISA with the inhibitors coated on the solid phase. HPLC fingerprint patterns of cyanogen bromide fragments of the two inhibitors were different. The inhibitory activity of the placental PAI was decreased by a factor of 3 after incubation with SDS, while that of the fibrosarcoma PAI was increased by a factor of 30. It is concluded that the two inhibitors show no detectable common antigenic determinants and most likely are products of different genes.

Antibodies↗
PubMed1987

Clinical pharmacology of tranexamic acid.

Tranexamic acid (AMCA) is a potent antifibrinolytic drug occurring in two isomeric forms; the antifibrinolytic potency resides in the transisomeric form. The main action of AMCA is blocking of the lysine-binding sites of the plasminogen molecule, which are of importance for the binding to fibrin. This prevents activation of plasminogen by plasminogen activator also absorbed to fibrin. AMCA can be administered perorally or intravenously and is excreted into the urine. It enters tissues and fluids in various concentrations and crosses the placenta. There is no evidence of a thrombogenic effect of AMCA, but in accordance with its action, it prolongs dissolution of fibrin deposits already formed. AMCA is a drug of high clinical value for the treatment of bleedings due to both systemic and local fibrinolysis.

Animals↗
PubMed1987

Specific plasminogen activator inhibitor of placental type PAI 2 occurring in amniotic fluid and cord blood.

Plasminogen activator inhibitor of placental type (PAI 2) occurs in a high molecular weight form (HMW) of 60 kd and a low molecular weight form (LMW) of 48 kd. Amniotic fluid and umbilical cord and maternal term plasma were examined for presence of PAI 2 using an enzyme-linked immunosorbent assay sandwich technique, purification on an affinity column (monoclonal antibodies coupled to Sepharose 4B), and immunoblotting. The median values of the concentrations of PAI 2 were 89, 13, and 75 micrograms/L, respectively. The HMW and LMW forms were found at about the same concentrations in amniotic fluid, but the LMW form predominated in cord blood, and the HMW form in maternal blood. The physiologic function of PAI 2 in the child is probably to prevent bleeding during the hazards of parturition.

Amniotic Fluid↗
PubMed1986

Release of both urokinase and tissue plasminogen activator from veins in vitro.

Specimens of human veins were incubated in culture media, in which the concentrations of urokinase (UK) and tissue plasminogen activator (t-PA) were determined by radioimmunoassay and immunoradiometric assay. Both UK and t-PA were released to the media, in which the concentration of plasminogen activators was correlated to the weight of the specimens. The release of t-PA was maximal on the first day, after which it rapidly decreased, and t-PA was not demonstrable after the third day of incubation. By contrast, UK was continuously liberated to the media during the study period of 5 days. The present results indicate that both UK and t-PA are present in the vein wall and probably released by different cells.

Culture Media↗
PubMed1986

Cellular localisation in placenta of placental type plasminogen activator inhibitor.

A specific plasminogen activator inhibitor is known to occur in placenta and in pregnancy plasma. Immunohistochemical methods with polyclonal and monoclonal antibodies against the inhibitor were used for its localisation in term placentas. Immunoreactive material was found in the trophoblastic epithelium. It was absent in the stroma of the chorion villi.

Antibodies↗
PubMed1986

Estrogen regulation of tissue plasminogen activator in a human melanoma cell line.

The influence of ethinylestradiol and the three natural estrogens, i.e. estrone, 17-beta-estradiol and estriol, was studied in a melanoma cell line producing a tissue-type plasminogen activator (t-PA). The cell cultures were exposed to the four estrogens by addition of the steroids dissolved in a weak alcoholic solution to the culture media, in which the released t-PA was assayed by an immunoradiometric method. Ethanol (0.76% w/v) stimulated the t-PA production, while no significant effect of the estrogens in the concentration of 1.7 X 10(-7) M was seen. By tenfold increase in estrogen concentration a highly significant reduction of t-PA levels was recorded in the cultures exposed to ethinylestradiol and 17-beta-estradiol. Estriol differed from these two estrogens in having rather weak inhibitory effect; whereas estrone in this concentration had toxic effect on melanoma cells. It was concluded that the present estrogens, in particular ethinylestradiol and 17-beta-estradiol, had a dose-dependent inhibitory effect on the production of t-PA in melanoma cell culture.

Cell Line↗
PubMed1986

Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease.

The ventral mesencephalon, containing the developing dopaminergic neurons of the substantia nigra-ventral tegmental region, was obtained from aborted human fetuses of 9-19 weeks of gestation. The tissue was grafted into the striatum of rats previously subjected to a 6-hydroxydopamine lesion of the mesostriatal dopamine pathway. The graft recipients were immunosuppressed by daily injections of Cyclosporin A. Amphetamine-induced motor asymmetry was reduced, and finally totally reversed, only in rats receiving grafts from the 9-week old fetal donor. The fluorescence microscopic analysis revealed large numbers of surviving dopamine neurons, and extensive fiber outgrowth into the host striatum, in these rats. By contrast, rats receiving grafts from 11-19 week old donors had at most only few surviving dopamine neurons. These results indicate that human fetal mesencephalic tissue may be an efficient source of dopamine neurons for functional intracerebral grafting in patients with Parkinson's disease.

Animals↗