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The fibrinolysin system and its relationship to disease in the newborn.

The fibrinolysin system is incomplete in newborn infants. Lack of serum plasminogen in premature newborn has an important role in the pathophysiology of the respiratory distress syndrome since alveolar fibrin deposits cannot be eliminated. Urokinase activated human plasmin has increased the survival rate of infants with respiratory distress syndrome. Plasminogen given I.V. at birth has reduced the incidence and the severity of respiratory distress syndrome, in a randomized double-blind study of 500 premature infants. Death in the plasminogen recipient group occurred only among infants born to mothers with bleeding complications of pregnancy. Plasmin inhibitors measured with a functional assay were the highest in this group of infants, serum plasminogen was the lowest; when activator and purified human plasminogen were added to the serum, fibrinolytic activity was elicited in excess of the plasminogen added. It is suggested that plasminogen and/or plasmin inhibitors may be abnormal fetal variants in infants born to mothers with bleeding complications.

Clinical Trials as Topic↗

Development, characterisation and diagnostic application of monoclonal antibodies against Yersinia pestis fibrinolysin and coagulase.

A library of monoclonal antibodies (MAbs) which recognised different epitopes of Yersinia pestis fibrinolysin (Fib) was developed. These MAbs were species-specific and demonstrated no cross-reaction in indirect immunofluorescence tests (IIFT) with other gram-negative bacteria possessing plasminogen activator activity. All the MAbs provided equally high levels of immunofluorescence with pPst+ Y. pestis strains cultivated at 37 degrees C and at 28 degrees C. In all cases, the MAbs inhibited both fibrinolytic and coagulase (Coag) activities of Y. pestis in Fib-activity inhibition and coagulase-activity inhibition reactions, and reacted with 35- and 37-kDa proteins of Y. pestis in immunoblotting, demonstrating bifunctional activity possibly similar to the properties of MAbs produced by hybrid hybridomas. On the basis of these and earlier studies, the immunochemical identity of Fib and Coag, two distinct subunits of a bifunctional fusion protein whose specific functional activity depends upon the temperature factor, was established. A new rapid, cheap, strictly specific and safe dot-ELISA based on the use of MAb against Y. pestis Fib (MAb-Fib) for reliable identification of Y. pestis strains was developed. This technique has great advantages over monoclonal diagnostic kits based on the use of MAb against Y. pestis fraction I (FI) because it allows detection of plague bacilli grown at 37 degrees C as well as at 28 degrees C. This dot-ELISA will be valuable as a clinical diagnostic tool and might be applicable to field studies and plague surveillance.

Animals↗

A Yersinia pestis-specific DNA fragment encodes temperature-dependent coagulase and fibrinolysin-associated phenotypes.

The effect of temperature on coagulase and fibrinolysin expression (Pla) by Yersinia pestis has been implicated in the transmission of plague by fleas. In an attempt to improve our understanding of this process, we have cloned, sequenced and characterized the gene encoding the Pla phenotypes in Y. pestis, and examined its temperature-dependent regulation. The coding region for this gene overlaps a 900bp Y. pestis-specific DNA fragment that we have previously shown to be capable of detecting plague bacilli in fleas. The pla gene contains a single open reading frame encoding 312 amino acids with a predicted molecular weight of 34.7 kD and a putative signal sequence of 20 amino acids. This coding region appears to be sufficient for both coagulase and fibrinolytic activities. In Y. pestis, modulation between coagulase and fibrinolytic activities is temperature-dependent: coagulase activity is most evident at temperatures below 30 degrees C but fibrinolytic activity increases with higher temperatures (greater than 30 degrees C), regardless of the temperature at which the bacteria are grown. Our results lead us to believe that this regulation occurs post-translationally. It is possible that the alternative forms of the Pla protein are essential to 'flea blockage' and subsequent transmission of the plague bacillus to animals.

Amino Acid Sequence↗

[Characterization of Yersinia pestis fibrinolysin using monoclonal antibody].

Immunochemical identity of Y. pestis fibrinolysin and coagulase is demonstrated using monoclonal antibodies. These substances are proven to exist as complex proteins with two independent activities. Possible causes of this phenomenon are discussed. Coagulase antigenic determinants are involved in specific fluorescence of Y. pestis cells grown at 28 degrees C. A new original method for screening the hybridomas producing monoclonal antibodies is proposed, based on inhibition of the functional activity of antigen.

Antibodies, Bacterial↗

Proteases during the growth of Ehrlich ascites tumor. I. The fibrinolysin system.

Component levels of the fibrinolysin system in the plasma and ascitic fluid of Swiss mice bearing Ehrlich ascites tumor cells were determined during a 15-day tumor growth time phase. During tumor growth, the concentration of plasminogen in the ascitic fluid decreased inversely to the total packed cell volume. Free plasmin was not present in the ascitic fluid nor was there any measurable plasminogen activator activity. Both antiplasmin activity and fibrinogen levels present in the fluid decreased during tumor growth. The nuclear and mitochondrial-microsomal subcellular fractions of the tumor cell exhibited plasminogen activator activity. No significant changes in the above parameters occurred in the plasma during the tumor growth period we studied.

Animals↗

[Necrolysis in burns using fibrinolysin and deoxyribonuclease].

Fibrolan was used altogether in 42 cases. This product, containing fibrinolysin and sesoxyribonuclease may be used favourably to remove necrotic tissues by conservative surgery until the extent of about 15 per cent burned surface. The necrolysis in burned injuries of grade II/2 is completed in the majority of the cases in 5-10 days, after this the development of the epithelium is finished in 5-10 days. If operation would be necessary, this can be performed after the end of the necrolysis with more favourable prospects. From the viewpoint of the technics of application and considering the cost too, the unguent is more favourable. The therapy had not to be interrupted because of complication or side effects.

Adult↗

[Bacteriophages of serologic group B converting synthesis of fibrinolysin in S. aureus].

On the basis of the length of tail, two morphological types of S. aureus bacteriophages of the serogroup B converting fibrinolysine were shown. The properties of the 22 S. aureus bacteriophages of the serologic group B were investigated. All of the investigated bacteriophages were classified as the morphological group II of the family Styloviridae on the basis of electron microscope analysis. The size of capsids of the examined bacteriophages was 53.85 +/- 1.05 nm and the tail length varied from 135.4 nm to 170.5 nm. All of them had the tail terminated in the basal plate. The lytic properties of the investigated bacteriophages were not identical. 7 of them showed features of lytic group I and 15 of lytic group III. The members of lytic group III had apparently a longer tail than bacteriophages of lytic group I.

Fibrinolysin↗

[Bacteriophages of serologic group F converting synthesis of fibrinolysin and beta toxin in S. aureus].

The properties of the 18 S. aureus bacteriophages of the serogroup F were investigated. The chosen bacteriophages were able to convert production of fibrinolysine inhibited synthesis of beta toxin. All of the investigated bacteriophages were classified as morphological group II of the family Styloviridae on the basis of the electron microscope analysis. The size of capsids of the examined bacteriophages was 54.10 +/- 0.80 nm and the tail length was from 206.1 nm to 311.9 nm. Most of them (15 bacteriophages) had the tail terminated in the basal plate. The lytic properties of the investigated bacteriophages were not identical. 11 of them showed features of lytic group III and 7 of lytic group V (miscellaneous).

Enterotoxins↗

[Inhibition of 5-fluorouracil-cisplatin-induced stomatitis by oral cryotherapy: use of an ice-bar containing fibrinolysin and deoxyribonuclease combine (Elase)].

Stomatitis caused by a combined chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP) is a serious problem in the course of treatment for patients with oral carcinoma. In the present study, we proposed a form of cryotherapy using an ice-bar containing fibrinolysin and deoxyribonuclease (Elase) to inhibit the stomatitis. The therapeutic effect of the ice-bar cryotherapy was evaluated in 20 patients with oral squamous cell carcinoma who were undergoing 5-FU-CDDP chemotherapy. Nine of the 20 patients were given the ice-bar cryotherapy while the remaining patients were not. As a result, although there was no significant difference between the incidence of stomatitis in the groups with and without the ice-bar cryotherapy, the incidence of severe stomatitis with ulcers and/or eating disturbance in the 11 cases without the ice-bar cryotherapy (90%) was significantly higher than that in the 9 cases with the cryotherapy (44%) (p < 0.05). However, no significant difference in the clinical response rate of the 5-FU-CDDP chemotherapy was observed between the two groups.

Adult↗

The fibrinolysin system in otitis media with effusion.

Middle ear effusions can cause the fibrinolytic dissolution of human fibrin clots. The data presented herein indicate that the highest level of fibrinolytic activity and general proteolytic activity is found in the serous effusions. The mucoid effusions show the lowest levels of fibrinolytic activity. The significance of the fibrinolytic activity in middle ear fluids is not fully understood. Plasmin, the active protease of the fibrinolysin system, is capable of activating a number of proteolytic systems, including the intrinsic coagulation system, the vasoactive peptide system, and the complement system. All the inflammatory mediator systems can promote increased vascular permeability, tissue edema, and leukocytic migration. The relation of these systems to inflammation in the middle ear may have a profound influence on the possible conversion of a simple middle ear effusion into chronic otitis media.

Aprotinin↗