Biomedical subjects
Publications and source records attributed to B Astedt.
The treatment of circumscribed plaque psoriasis with a carbon dioxide (CO2) laser as an outpatient procedure is reported in three patients. The growth of new tissue over the healed laser vaporized area was similar to normal skin and has remained free of psoriasis during a follow-up of 3 X 5 years. Laser vaporization appears to be a simple and effective alternative to conventional therapy in cases of plaque psoriasis.
The content of tissue plasminogen activator inhibitor (t-PA-I), and of specific pregnancy plasma-PA-I reacting with antibodies to placental-PA-I, was measured in platelet-poor plasma (PPP), platelet-rich plasma (PRP), serum and platelet lysate, both from pregnant women and healthy non-pregnant (male or female) controls. Inhibitory activity was much higher in PPP from pregnant women than in PPP from controls, though it was comparable in platelet lysates both from pregnant women and from controls. The specific pregnancy Plasma-PA-I was present in high concentration in pregnancy PPP, but absent in PPP from the controls and also absent in platelet lysates from both pregnant women and controls. The results show that the specific pregnancy plasma-PA-I is not identical to either the PA-I in platelet lysate or to the PA-I in PPP from non-pregnant controls.
A specific plasminogen activator inhibitor was isolated from the plasma of pregnant women by matrix-bound, cross reacting monoclonal antibodies against placental plasminogen activator inhibitor. The pregnancy plasma plasminogen activator inhibitor (PP-PA-I) was found to be immunologically different from the inhibitor produced by endothelial cells. Its molecular weight was 70 000 daltons. It formed complexes with urokinase (u-PA) and with plasminogen activator of the tissue type (t-PA), similar to those formed by the placental plasminogen activator inhibitor (PI-PA-I). It did not inhibit plasmin. For measuring PP-PA-I, an enzyme-linked immunosorbent assay (ELISA) was designed using monoclonal and polyclonal antibodies against the placental inhibitor. Concentrations of PP-PA-I increased successively during pregnancy, and fell sharply after delivery. This inhibitor could not be detected in normal non-pregnancy plasma. The results indicate that the inhibitor isolated from pregnancy plasma is responsible for the depressed fibrinolytic activity during pregnancy, and that the placenta is the source of the inhibitor.
Ultrasound scan for detection of ovarian enlargements was performed in a target group of out-patients attending the clinic for various reasons in the 40-70 years range. Overall 805 women were examined, in 99% of whom the ovaries and/or their vessels could be identified. Pathological findings were suspected in 83 patients at the first scan, and were confirmed in 50 after a repeat scan, 39 of whom subsequently underwent surgery. Various ovarian lesions were found in 35 women, including five mucinous and serous cystadenomas, one carcinoma, two borderline tumours, and a cancer of the caecum. None of the borderline or malignant ovarian lesions were found by manual pelvic examination. Ultrasound screening appears to be a useful diagnostic aid, though its usefulness might be further improved if other risk factors such as heredity and period of ovulatory activity are taken into consideration.
In women undergoing conization of the uterine cervix, peripheral blood samples and blood samples from the cone cavity were obtained and analysed for their concentration of plasminogen activator of tissue type (t-PA) and of urokinase type (u-PA) and the concentration of fibrinogen/fibrin degradation products (FDP). A significant increase was found for t-PA (p less than 0.002) and u-PA (p less than 0.0002) as well as for FDP (p less than 0.002) in blood from the cone cavity compared with peripheral blood. The finding of increased liberation of plasminogen activators strengthens the rationale for administration of synthetic inhibitors of fibrinolysis to reduce the frequency of bleeding complications at conization.
Plasminogen activators in alveolar bone in man was studied in quenching experiments by a fibrin slide technique with addition of monospecific antibodies against tissue plasminogen activators (t-PA) and urokinase (u-PA). The plasminogen activator activity was quenched in the slides with anti-t-PA. No quenching was observed in the slides with anti-u-PA. This does not exclude the possibility that enzymatically inactive pre-urokinase is present.
Two types of plasminogen activator (PA), t-PA (tissue type) and u-PA (urokinase type), are released from endometrial tissue in organ culture, as judged by immunological identification and molecular weight. Addition of estradiol to the medium greatly enhanced the release of u-PA, whereas that of t-PA was not low. Addition of progesterone, on the other hand, after priming of the endometrial tissue with estradiol, resulted in a much lower release of both types of PA. This pattern of PA release in response to hormonal stimulation in vitro agrees with previous observations of the PA activity of endometrial secretion in vivo. Endometrial tissue also released a PA inhibitor with molecular weight of approximately 50,000, which complexed both t-PA and u-PA. In cultures stimulated with estradiol the amount of free u-PA increased gradually during incubation and minor amounts of free t-PA appeared after 4-6 days culture. The amount of complexes, and thus the amount of PA inhibitor also increased under influence of estradiol. In cultures stimulated with progesterone, on the other hand, only minor amounts of free u-PA and no free t-PA was detected. The inhibitor might be of either the endothelial or the placental type, or both.
Treatment of venous thrombosis during pregnancy is not without risks. Therefore diagnosis has been made by phlebography. Streptokinase therapy is accompanied with bleedings and needs a precise indication. 4 women have been operated on by thrombectomy. Dicumaroles cause fetal demages and are not suitable for prophylaxis of recurrences. Heparin is the treatment of choice, partly by self injection. During parturition a short time change to low molecular dextran is recommended.
A monoclonal antibody of IgG2a-type was obtained against a specific fast acting plasminogen activator inhibitor found in placenta. The placental inhibitor was purified by affinity chromatography using the monoclonal antibody and additionally in a FPLC-system. A strong complex formation was found between the inhibitor and urokinase and also with the two-chain form of plasminogen activator of the tissue-type. A weaker complex was found between the placental inhibitor and the one-chain form of the tissue-type activator.
The interaction of tissue plasminogen activator derived from a melanoma cell line with a specific plasminogen activator inhibitor from placental tissue, which inhibits urokinase and tissue plasminogen activator but not plasmin, was studied. Tissue plasminogen activator exists in two forms, a one chain and a two chain molecule. It was found that the two enzyme species each form 1:1 complexes with the inhibitor and that the two chain enzyme binds the inhibitor very strongly, Ki = 3 X 10(-10) mol/l, whereas the one chain enzyme forms a much weaker complex, Ki is approximately 10(-7) to 10(-8) mol/l. Substrate hydrolysis is much more efficiently catalysed by the two chain plasminogen activator than by the one chain activator.
Immunoreactive plasminogen activators were studied in tissue sections using a peroxidase method and monospecific antibodies to tissue plasminogen activator produced by a melanoma. Tissue plasminogen activator reactivity was found in skin melanomas and in endothelial and smooth muscle cells of arteries and veins. Vessels of the umbilical cord showed higher reactivity than peripheral vessels. Only faint antiurokinase reactivity was found. By means of the fibrin slide technique, fibrinolytic activity could be shown in peripheral vessel walls but not in the umbilical cord, which suggests that immunoreactivity of tissue plasminogen activator bound to an inhibitor can also be demonstrated. This method may be a useful tool in further studies of tissue plasminogen activator in physiological as well as pathological processes.
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A case of prolapse of the small bowel through the vagina after gynaecologic operations is described. This is a very rare complication and up to date only eleven cases have been described. Measures to prevent this complication are discussed.
The influence of ethinylestradiol (EE2) and d-norgestrel (d-Ng) was studied in a melanoma cell line producing a tissue-type plasminogen activator (t-PA) very similar to or identical with the t-PA isolated in extracts from human uterus. The cell cultures were exposed to the two contraceptive steroids by addition of EE2 or d-Ng dissolved in a week alcoholic solution to the culture media, in which the released t-PA was assayed by an immunoradiometric method. A strongly stimulating effect of ethanol (0.76% w/v) on the t-PA production was demonstrated. Whereas, EE2 in the concentration of 1.7 X 10(-7)M and d-Ng in the concentration of 8.6 X 10(-7)M both caused a significantly reduced secretion of t-PA, and this effect was independent of whether the cell cultures were grown to confluency in the presence of the two synthetic steroids or not. It was concluded, that the two contraceptive steroids had an inhibitory effect on the production of t-PA in melanoma cell culture.
In organ cultures of human ureters, plasminogen activators were released into the medium. Unlike most tissue cultures that release mainly urokinase (UK), the activators released by ureter cultures were predominantly of the tissue-type (t-PA), as shown by radioimmunoassay. Using affinity chromatography it was possible to distinguish two activities. One minor fraction was quenched by antibodies against UK, but not by antibodies against t-PA. The other activity was quenched by antibodies against t-PA, but not by those against UK, and required the presence of fibrin to activate plasminogen. Because of the large amount of t-PA, cells derived from human ureter might well prove to be a useful source of t-PA.
The release of tissue-type plasminogen activator (t-PA) from incubated specimens of human veins was investigated by an immunoradiometric determination of the concentration of t-PA in the medium. The initial release of t-PA was strongly correlated to the weight of the incubated specimens. T-PA was not demonstrable after the third day of incubation. The addition of d-norgestrel (83.3 ng/ml) to the medium significantly stimulated the release of t-PA; whereas, ethinylestradiol (16.6 ng/ml) did not have an effect.
Plasminogen-activator activity was examined qualitatively in normal and malignant mucosa of the oral cavity in humans, using an immunological histochemical fibrin slide technique. No fibrinolytic activity was observed in sections of normal mucosa when monospecific antibodies against a melanoma cell activator (anti-MA) were added. Antibodies against urokinase (anti-UK) did not react on the fibrinolytic activity which indicates that the activator is of tissue type. In malignant tissue, fibrinolytic activity was completely blocked by a mixture of anti-MA and anti-UK.