Search PubMed⌕ Search

Biomedical subjects

B Astedt

Publications and source records attributed to B Astedt.

At least 91 records · Page 5Linked to original sources

Differential inhibition of two molecular forms of melanoma cell plasminogen activator by a placental inhibitor.

The inhibitory effect of a placental urokinase inhibitor on the one- and two-chain form of melanoma cell derived plasminogen activator (PA) was investigated. The melanoma cell PA has been shown to be similar to or identical with the PA found in normal tissue. With constant concentration of placental inhibitor the rate of inhibition of the two-chain form was fast in contrast to that of the one-chain form. With constant incubation time but increasing concentrations of the placental inhibitor the two-chain form was inactivated to a greater extent at lower concentrations of placental inhibitor than was the one-chain form. The increased reactivity of the two-chain form of melanoma PA compared to the single-chain form may explain the role of tissue PA in achieving high local concentrations of PA activity which facilitate selective fibrin clot lysis.

Fibrinolysis↗

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↗

[Immunoradiometric determination of blood/tissue plasminogen activators in thrombophilia].

Immunoradiometric determination of the blood/tissue plasminogen activator was in plasma from patients before and after response to venous occlusion, infusion of DDAVP or exercise. The raise in the level of plasminogen activator was most pronounced after venous occlusion. In patients who earlier had had verified thrombosis the levels of plasminogen activator compared to normals did not show any significant difference.

Contraceptives, Oral↗

Characterisation of the vascular plasminogen activator from the pig ear.

Spontaneously released plasminogen activator after perfusion with 0.9% NaCl of isolated pig ear was purified by affinity chromatography on Heparin-Sepharose. The molecular weight of the plasminogen activator is about 60,000 Daltons, the isoelectric point lies at pH 7.6. The enzyme is most stable at neutral pH. At 37 degrees C it is stable for two hours. The activator did not show lytic activity either on heated or on PAMBA fibrin plates. The activity of the activator was inhibited by exposure to DFP and PMSF but not by exposure to TLCK and TPCK, suggesting that it is an enzyme with an active-site residue which belongs to the tissue-type activators.

Animals↗

Reduced plasminogen activator content of the endometrium in oral contraceptive users.

Human endometrium was found to contain two different plasminogen activators, urokinase and tissue activator. Urokinase was released in higher amounts from endometrial tissue explants obtained in the midcycle phase than from those obtained in the luteal phase. Plasminogen activator activity of the culture medium followed the same pattern. Treatment of postmenopausal patients with ethinylestradiol resulted in liberation of urokinase and tissue activator from endometrial explants in concentrations similar to those found in the normal midcycle phase. In contrast, treatment with oral contraceptives (OCs), containing ethinylestradiol and a progestagen, resulted in lowered release of both activators, even lower than was found during the normal luteal phase. Also the amounts of extractable urokinase from endometrial tissue samples were significantly lower in OC-users than in non-users. Estradiol seems to have a stimulatory effect on the release of plasminogen activators from the endometrium; whereas, gestagens depress the content and release of activators. The low content of plasminogen activators in the endometrium explains the reduced menstrual bleedings found in OC-users.

Contraceptives, Oral↗

Occurrence of both urokinase and tissue plasminogen activator in the human endometrium.

The presence of two different plasminogen activators, urokinase and tissue activator, in the endometrium was demonstrated immunologically. Tissue activator was prevalent and urokinase was present in only minor amounts in endometrial tissue extractions. In tissue culture, on the contrary, endometrial explants released more urokinase than tissue activator into the medium and the fibrinolytic activity of the medium was mainly due to urokinase. This may reflect different modes of intracellular storage of the two activators, or the presence of a pre-urokinase which is immunologically different from urokinase and which is activated upon release. The amount of urokinase and fibrinolytic activity released into the culture medium was higher when endometrium samples had been obtained in the midcycle phase than in the proliferative and luteal phases. This pattern mimics the in vivo release of plasminogen activator from the endometrium into the uterine fluid. Endometrium obtained from IUD-users had a higher content of urokinase than that obtained from non-users.

Culture Media↗

Laser miniconization in mild and moderate dysplasia of the uterine cervix.

Mass cytologic screening for cervical cancer often reveals only mild dysplasia not indicating conization but necessitating continual checkup. Such routine checkups are often insufficient, beside which the patients find them frustrating. Therefore a new method, called miniconization, for treatment of patients with vaginal smears showing mild or moderate dysplasia (cervical intraepithelial neoplasia/CIN/I-II), was developed. With the CO2 laser handpiece a 5-mm-thick disc of the cervix, including the whole transformation zone, was removed. This was followed by endocervical curettage. The advantage of the method over cryosurgery, electrocoagulation, and laser vaporization, for example, is that the tissue specimen as a whole disc including the transformation zone can be sectioned and examined histologically. Another advantage is the decreased risk of postoperative bleeding, which enables ambulant care. One hundred and fifty-one patients have hitherto been treated and carcinoma in situ has been found in 15.2% and microinvasive carcinoma in 1.3% of all these patients in whom vaginal smears showed mild or moderate dysplasia (CIN I-II).

Adult↗

Immunological characterisation of plasminogen activators in the human vessel wall.

A histochemical technique was used to identify the activity of the plasminogen activator (PA) in the vessel wall of veins. Antibodies against melanoma cell activator and urokinase (UK), both raised in goats, were mixed into the fibrin film. The PA activity was quenched by the antibodies against melanoma activator but remained unchanged when antibodies against UK, or an IgG preparation of normal goat serum, was mixed in the fibrin film. The results of this study show that the PA activity in the vein vessel wall is immunologically similar to or identical to the PA derived from melanoma cells which has previously been shown to cross-react with the tissue-like PA. No UK-like activity was present in the vessel wall.

Antibodies↗

Higher fibrinolytic activity in human endometrium in direct contact with an IUD.

From 18 apparently healthy women wearing a copper-IUD, endometrial biopsy specimens were obtained under hysteroscopic control, both from the site of the IUD and from a distant area. The fibrinolytic activity proved significantly higher in the former specimens than in the latter. The results provide a theoretical basis for the development of an IUD which releases a synthetic inhibitor of fibrinolysis.

Endometrium↗

[Laser miniconization - a new method of treating mild and moderate cervix dysplasia].

The miniconization by carbon dioxid laser is a non-destructive method for treatment of mild and moderate dysplasia of the uterine cervix permitting an adequate histopathological interpretation of the whole transformation zone. The risk of postoperative haemorrhage is minimal which enables ambulant care. 413 patients have hitherto been treated and we have found carcinoma in situ in 16.7%, micro-invasive carcinoma in 1.2% and invasive carcinoma in 0.25%.

Adolescent↗

Kinetics of the reaction between urokinase and an inhibitor of fibrinolysis from placental tissue.

The interaction of urokinase (EC 3.4.21.31) and a protein proteinase inhibitor of fibrinolysis partially purified from placental tissue, which inhibits urokinase but not plasmin, was investigated. The preparations of the inhibitor contained no other known proteinase inhibitors. It was found that a 1:1 complex is formed and that the reaction proceeds as a second order, one step process, the association rate constant of which is 4.5 10(6) M-1 S-1 at pH 8.4, 37 degrees C and 3.0 10(6) M-1 S-1 at pH 7.3, 37 degrees C. The binding is very tight, the dissociation constant of the inhibitor-urokinase complex was estimated to be Ki less than or equal to 10(-11) M.

Blood Proteins↗

Release of proteolytic enzymes from leucocytes attached to IUDs.

The leucocytes adhering to intrauterine devices (IUDs) were predominantly mononuclear phagocytic cells (MPCs) and granulocytes. These cells released elastase and a plasminogen activator in the culture medium. The plasminogen activator was found to be immunologically identical to tissue activator, and the release pattern indicated that the activator as well as elastase were released from both MPCs and granulocytes. Thus, the results suggest the generalized conclusion that both MPCs and granulocytes release the tissue activator-type of plasminogen activator. The urokinase-type of plasminogen activator, which was detected initially in some cultures, may originate from endometrial tissue fragments adhering to the IUD. IUDs removed in the end of the menstrual phase and in the midcycle phase released more plasminogen activator than did devices removed at the proliferative and luteal phases. No such cyclic variation was found for the release of elastase.

Female↗

Coagulation and fibrinolysis in pregnancy complicated by intrauterine growth retardation.

In a prospective study, blood from women in the 19th and 32nd week of pregnancy was analyzed for fibrinogen, prothrombin complex (P & P), F, V, F VIII:C, F VIIIR:Ag, the VIIIR:Ag/VIII:C ratio, F IX, F XII, F XIII, antithrombin III, alpha 2-macroglobulin, alpha 1-antitrypsin, alpha 2-antiplasmin, the inhibitor of plasminogen activation and fibrinogen degradation products. In normal pregnancies all the coagulation factors except F XIII were markedly increased, as were alpha 1-antitrypsin and the inhibitor of plasminogen activation. Pregnancy did not influence the levels of antithrombin III, alpha 2-macroglobulin or alpha 2-antiplasmin. Peripheral blood from women with growth retarded fetuses differed in that the levels of P & P, F XII (in the 19th week) and the inhibitor of plasminogen activation (in the 19th and 32nd weeks) were lower. The level of F XIII was higher in the 32nd week. A low grade activation of the coagulation system is suggested as one possible factor in the pathogenesis of intrauterine growth retardation, which emphasized the value of heparin treatment in certain cases with this syndrome.

Blood Coagulation Disorders↗