Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SM-4300, a newly developed human immunoglobulin for intravenous use, was administered to 6 patients in the pediatric field. Two cases out of 3 cases with immunodeficiency syndrome were studied in terms of absorption and excretion of SM-4300 and all of them were observed effect of preventive bacterial infection. Three cases were administered combination therapy with SM-4300 and antibiotics. Two cases were pneumonia and 1 case was pleurisy. The following results were obtained. Two cases with immunodeficiency syndrome were observed serum levels of immuno gammaglobulin before and after administration of SM-4300. At 2-3 hours after the administration of SM-4300, the serum levels got to peak and the half-lives were 22.1 days and 22.6 days, respectively. The half-lives of SM-4300 were similar to plasmin or polyethylene glycol treated and sulfonated human immunoglobulin. The clinical effects of substitution therapy against 3 patients with immunodeficiency syndrome were observed. Through the administration of SM-4300 every 18 to 21 days for 6 months, 1 case was doing well. One case with chronic bronchitis and otitis media was hanging in the balance as well as she has been administered other immunoglobulin preparations. The last case didn't control the serum levels of immunoglobulin because he did not visit a hospital until incidence of infectious disease.
...
PMID:[Clinical trial of SM-4300 in the pediatric field]. 407 25

An experimental disseminated intravascular coagulation (DIC) was induced in female CD rats by the intravenous administration of living bacteria (9.5 x 10(7) cfu Klebsiella pneumoniae), sublethal (5 mg/kg) or lethal (50 mg/kg) lipopolysaccharide (LPS), or tissue factor (1.5 micrograms/kg i.v. bolus or 0.4 micrograms/kg x hr i.v. infusion). We used a new fibrin monomer (FM) assay to follow the course of DIC. FM were detected by their ability to stimulate the tissue-type (t-PA) plasminogen activator dependent conversion of plasminogen to plasmin by a chromogenic assay. Miniplasminogen was used instead of plasminogen to avoid interference of the assay by alpha 2-antiplasmin. As a marker of DIC, elevated levels of FM were observed with all DIC-inducing agents (plasma levels were up to 90 micrograms/ml). The kinetics of FM formation were similar to the course of thrombin-antithrombin III (TAT) levels (maximal plasma levels 70 ng/ml); however, in the bacterial infection group, both parameters rose after a lag phase of about 1 hr. A 4 hr infusion of the highly specific thrombin inhibitor recombinant (rec.) hirudin (0.125 mg/kg x hr) resulted in a decrease of FM levels from 89.2 +/- 14.4 micrograms/ml in the LPS group (n = 10) to 27.4 +/- 11.2 micrograms/ml in the rec. hirudin group (n = 10; P < 0.001). The respective values for TAT levels were 73.1 +/- 19.7 micrograms/ml in the LPS group and 52.7 +/- 15.7 ng/ml in the rec. hirudin group (P < 0.001). Other coagulation parameters, such as platelets, fibrinogen, and fibrin(ogen) degradation products, were ameliorated accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Formation of fibrin monomers in experimental disseminated intravascular coagulation and its inhibition by recombinant hirudin. 805 64

Twenty-five leg ulcer exudate samples from 17 patients with chronic non-healing venous leg ulcer were analyzed for proteolytic activity using radial caseinolysis procedures and zymographic analysis, and for fibronectin fragmentation using immunoblotting technology. Caseinolytic activity was detected in 21 of the 25 samples. A minority of them were inhibited (3 were totally, 6 partially inhibited) by aprotinin, a serine proteinase inhibitor, suggesting that proteinase(s) other than plasmin were also responsible for the caseinolysis. In zymographic analysis, 23 of the 25 samples showed positive reactions for enzyme activities comigrating with plasmin and urokinase-type plasminogen activator. Fibronectin fragmentation, another sign of proteolytic activity, was seen in all but 2 ulcers. No correlation was seen between bacterial infection or inflammatory cells and the above parameters in the wound fluid. Acute wound fluid collected from the donor sites of patients undergoing split skin grafting was used as a control. In the control specimens no proteolytic activity was found during the days following operation. These results show that there is proteolytic activity in the chronic ulcer exudate and support the possibility that the proteolytic activity and consequent fibronectin fragmentation may be related to the retarded epithelization and ulcer healing.
...
PMID:Proteolytic activity in leg ulcer exudate. 815 67

Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) are the most important factors involved in the regulation of blood fibrinolysis. t-PA converts zymogen plasminogen to plasmin on the surface of endothelial cells to maintain blood fluidity and on the surface of the thrombus to efficiently lyse the thrombus. In circulating plasma, PAI-1 inactivates t-PA by forming an equimolar complex with t-PA to suppress the hyperfibrinolysis of the blood. Both proteins are synthesized by the vascular endothelial cells and secreted from the cells in resting state and in response to several stimuli such as thrombin, endotoxin, cytokines and growth factors. In various diseases such as DIC, thromboembolism and bacterial infection, the plasma concentrations of those two factors vary as a consequence of several stimuli, representing the altered fibrinolytic balance caused by the disease. Measurements of these factors and evaluation of the fibrinolytic balance will be important for determination of the most appropriate method of treatment. Moreover, the high plasma concentration of PAI-1 will be a prognostic marker of the disease and may be a risk factor of thrombotic events. In clinical treatment, t-PA is now widely used as a valuable fibrinolytic agent especially in myocardial infarction.
...
PMID:[Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)]. 817 42

Vascular pathophysiology at the sites of bacterial infection and cancerous tissues share numerous common events similar to inflammatory tissue. Among them enhanced vascular permeability is the universal and hallmark event mediated by bradykinin. All 16 or more bacterial or fungal proteases we have examined activated one or more steps of the kinin generating Hageman-factor-kallikrein cascade. In the meantime, most of the microbial proteases rapidly inactivated various plasma inhibitors such as alpha 1-protease inhibitor and alpha 2-macroglobulin. In addition to the extracellular proteases, bacterial cell wall components (negatively charged LPS) of gram-negative bacteria and teichoic acid moieties of gram-positive bacteria activate the Hageman-factor-kallikrein system and exert hypotensive effects via kinin generation. Endotoxin (LPS) also induces nitric oxide synthase (NOS) which appears to exhibit a rather slow, but significant, effect in relaxing the vascular tone of the infected animal (thus hypotension). Furthermore, bacterial proteases can activate the matrix metalloproteinase (collagenase) resulting in exacerbation of tissue injury in the diseased animal. Many tumor cells or tissues excrete plasminogen activator, and hence activate plasminogen. The plasmin thus generated activates procollagenases, as well as the Hageman-factor-kallikrein system, resulting in pronounced extravasation. Fluid accumulation in pleural and ascitic carcinomatoses is largely due to the activated bradykinin-generating system. We can also demonstrate and control enhanced vascular permeability using kallikrein inhibitors, especially the polymer-conjugated soybean trypsin inhibitor which exhibits a prolonged plasma t1/2, kinin antagonists, NOS inhibitors, NO scavengers, inhibitors of prostaglandins and others. Bacterial proteases induce shock in mice which can be prevented by the soybean trypsin inhibitor by blocking the kallikrein-kinin cascade. Therapeutic use of kinin antagonists and a kallikrein inhibitor has been made for infectious diseases such as septicemia and in tumor pathology.
...
PMID:Bradykinin and nitric oxide in infectious disease and cancer. 885 54

The plasminogen activator, surface protease Pla, of the plague bacterium Yersinia pestis is an important virulence factor that enables the spread of Y. pestis from subcutaneous sites into circulation. Pla-expressing Y. pestis and recombinant Escherichia coli formed active plasmin in the presence of the major human plasmin inhibitor, alpha2-antiplasmin, and the bacteria were found to inactivate alpha2-antiplasmin. In contrast, only poor plasminogen activation and no cleavage of alpha2-antiplasmin was observed with recombinant bacteria expressing the homologous gene ompT from E. coli. A beta-barrel topology model for Pla and OmpT predicted 10 transmembrane beta-strands and five surface-exposed loops L1-L5. Hybrid Pla-OmpT proteins were created by substituting each of the loops between Pla and OmpT. Analysis of the hybrid molecules suggested a critical role of L3 and L4 in the substrate specificity of Pla towards plasminogen and alpha2-antiplasmin. Substitution analysis at 25 surface-located residues showed the importance of the conserved residues H101, H208, D84, D86, D206 and S99 for the proteolytic activity of Pla-expressing recombinant E. coli. The mature alpha-Pla of 292 amino acids was processed into beta-Pla by an autoprocessing cleavage at residue K262, and residues important for the self-recognition of Pla were identified. Prevention of autoprocessing of Pla, however, had no detectable effect on plasminogen activation or cleavage of alpha2-antiplasmin. Cleavage of alpha2-antiplasmin and plasminogen activation were influenced by residue R211 in L4 as well as by unidentified residues in L3. OmpT, which is not associated with invasive bacterial disease, was converted into a Pla-like protease by deleting residues D214 and P215, by substituting residue K217 for R217 in L4 of OmpT and also by substituting the entire L3 with that from Pla. This simple modification of the surface loops and the substrate specificity of OmpT exemplifies the evolution of a housekeeping protein into a virulence factor by subtle mutations at critical protein regions. We propose that inactivation of alpha2-antiplasmin by Pla of Y. pestis promotes uncontrolled proteolysis and contributes to the invasive character of plague.
...
PMID:Protein regions important for plasminogen activation and inactivation of alpha2-antiplasmin in the surface protease Pla of Yersinia pestis. 1140 15

Triethylene thiophosphoramide, an alkylating agent of value as a palliative in cases of neoplastic disease and reticulosis, has been effective in preventing vascularization of the cornea when used locally. Since recurrent pterygium, a persistent clinical problem, particularly in the Western states, is preceded by corneal vascularization and fibroplastic proliferation, it is possible that this drug when used topically may be useful in obviating to some extent the use of radiation, which must be used with great caution to avoid the production of cataract. In the treatment of gram-negative bacterial infection, especially Pseudomonas aeruginosa, the drug colistin has been known to be effective in some cases which were not helped by other antibiotics, including polymixin B. In the field of virus infections, a major breakthrough may have come about by the discovery that 5-iodo-2-deoxyuridine (IDU) attacks the herpes cirrus in the cornea as a metabolic antagonist. Animal experiments and some clinical studies have confirmed its effectiveness as compared with other therapeutic measures in selected cases. In the treatment of ocular problems resulting from systemic disease fibrinolysin (plasmin) has apparently caused dissolution of the clot and restoration of circulation in some cases of retinal artery occlusion. Severe diabetic retinopathy in younger diabetic patients has been shown to regress in certain cases treated by hypophysectomy or radiation of the pituitary gland employing the cyclotron. This gland is also associated intimately with the exophthalmos of thyroid origin, and its action may be aggravated by the use of ACTH or steroids.
...
PMID:Recent developments in ocular therapeutics. 1399 13

Staphylokinase is a 136 aa long bacteriophage encoded protein expressed by lysogenic strains of Staphylococcus aureus. Present understanding of the role of staphylokinase during bacterial infection is based on its interaction with the host proteins, alpha-defensins and plasminogen. alpha-Defensins are bactericidal peptides originating from human neutrophils. Binding of staphylokinase to alpha-defensins abolishes their bactericidal properties, which makes staphylokinase a vital tool for staphylococcal resistance to host innate immunity. Complex binding between staphylokinase and plasminogen results in the formation of active plasmin, a broad-spectrum proteolytic enzyme facilitating bacterial penetration into the surrounding tissues. We have recently shown high levels of staphylokinase expression in clinical isolates of skin and mucosal origin and relative low levels in isolates invading internal organs. These findings are supported by sepsis studies using isogenic S. aureus strains demonstrating increased bacterial load in the absence of staphylokinase production. Our observations indicate that staphylokinase favours symbiosis of staphylococci with the host that makes it an important colonization factor.
...
PMID:Staphylococcus aureus: Staphylokinase. 1611 12

Aside from its enzymatic function in the glycolytic pathway, alpha-enolase (ENO1) has been implicated in numerous diseases, including metastatic cancer, autoimmune disorders, ischaemia and bacterial infection. The disease-related roles of ENO1 are mostly attributed to its immunogenic capacity, DNA-binding ability and plasmin(ogen) receptor function, which are significantly affected by its three-dimensional structure and surface properties, rather than its enzymatic activity. Here, the crystal structure of human ENO1 (hENO1) is presented at 2.2 A resolution. Despite its high sequence similarity to other enolases, the hENO1 structure exhibits distinct surface properties, explaining its various activities, including plasmin(ogen) and DNA binding.
...
PMID:Structure of human alpha-enolase (hENO1), a multifunctional glycolytic enzyme. 1856 Jan 53

The immune response to infection includes activation of the blood clotting system, leading to extravascular fibrin deposition to limit the spread of invasive microorganisms. Some bacteria have evolved mechanisms to counteract this host response. Pla, a member of the omptin family of Gram-negative bacterial proteases, promotes the invasiveness of the plague bacterium, Yersinia pestis, by activating plasminogen to plasmin to digest fibrin. We now show that the endogenous anticoagulant tissue factor pathway inhibitor (TFPI) is also highly sensitive to proteolysis by Pla and its orthologs OmpT in Escherichia coli and PgtE in Salmonella enterica serovar Typhimurium. Using gene deletions, we demonstrate that bacterial inactivation of TFPI requires omptin expression. TFPI inactivation is mediated by proteolysis since Western blot analysis showed that TFPI cleavage correlated with loss of anticoagulant function in clotting assays. Rates of TFPI inactivation were much higher than rates of plasminogen activation, indicating that TFPI is a better substrate for omptins. We hypothesize that TFPI has evolved sensitivity to proteolytic inactivation by bacterial omptins to potentiate procoagulant responses to bacterial infection. This may contribute to the hemostatic imbalance in disseminated intravascular coagulation and other coagulopathies accompanying severe sepsis.
...
PMID:Proteolytic inactivation of tissue factor pathway inhibitor by bacterial omptins. 1898 66


1 2 Next >>

---