PubMed · 13694439
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
S I COHEN, R WARREN. 1961-01-19. Fibrinolysis.. https://doi.org/10.1056/nejm196101192640306
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Components of the fibrinolytic pathway contribute to diverse pathways in many tissues, in addition to their well-recognized role in degradation of fibrin clots. In this study of nasal mucosa, we investigated the presence of mRNA of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor-1 (PAI-1), and plasminogen activator inhibitor-2 (PAI-2) using reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization, and compared these results with their localization in immunostained tissues. According to real-time RT-PCR results, t-PA, u-PA, PAI-1, and PAI-2 mRNA were noted in human nasal mucosa. Particularly, expression of u-PA and PAI-1 mRNA was significantly high in allergic nasal mucosa in comparison with normal mucosa. t-PA mRNA was detected in endothelial cells and epithelium in normal nasal mucosa. t-PA mRNA was detected in mucous cells of allergic submucosal glands, but not in normal glands. In allergic rhinitis, u-PA and PAI-2 mRNA were detected in mucinous cells and epithelium, and PAI-1 mRNA was detected in serous cells and epithelium. Expression of u-PA and PAI-1 mRNA in normal nasal tissues was decreased in contrast to that in allergic nasal tissues. u-PA staining was observed in mucous cells of allergic submucosal glands and the staining pattern of PAI-2 was similar to that of u-PA. PAI-1 was present in serous cells of submucosal glands from allergy samples, while epithelial cells were almost devoid of stain. In contrast, with allergy, immunohistochemical staining of t-PA was negative in submucosal glands, though positive in endothelial cells and epithelium. However, the expression of t-PA mRNA in allergic nasal mucosa was noted in mucous cells. In fibrin autography of nasal discharge, u-PA was markedly activated in the allergic patient. These results suggest that t-PA synthesized in mucous cells is promptly secreted and modifies watery nasal discharge in allergic rhinitis, and that u-PA activity may help the passage of large amounts of rhinorrhea by also reducing its viscosity. A lot of cellular infiltration (eosinophils in particular) was recognized in allergic nasal mucosa. It is most likely that the modifications in expression of PAs and PAIs are due to the local release of cytokines or growth factors from these inflammatory and immune cells.
A failure of hemostasis and consequent formation of blood clots in the circulatory system can produce severe outcomes such as stroke and myocardial infraction. Pathological development of blood clots requires clinical intervention with fibrinolytic agents such as urokinase, tissue plasminogen activator and streptokinase. This review deals with streptokinase as a clinically important and cost-effective plasminogen activator. The aspects discussed include: the mode of action; the structure and structure-function relationships; the structural modifications for improving functionality; recombinant streptokinase; microbial production; and recovery of this protein from crude broths.
Ultrasound of 2 MHz frequency and 1.2 W/cm(2) acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% +/-6.9% which is significantly higher (p<0.0001) than in the group of clots treated with rt-PA only (19.9% +/-4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 +/-2513 ng/ml vs. 2364 +/-725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p<0.0001), and broadened the zone of lysis from 8.9 +/-2.6 microm to 21.2 +/-7.2 microm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.