Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to investigate the mechanism for hyperfibrinolysis in the ascites associated with peritonitis carcinomatosa. Various combinations of mouse MM2 ascites tumor (MAT) and mouse peritoneum (Mpr) and plasminogen (Plg) were incubated in medium 199 and the fibrinolytic activity of each preparation was assayed. 1) Among the preparations, the preparation of MAT plus Mpr plus Plg showed particularly high fibrinolytic activity. This suggests that plasminogen activator (PA) production is initiated by MAT together with Mpr. 2) Equal volumes of the ultrafiltrate and the concentrate of supernatant from MAT were each separately treated with a Mpr plus Plg preparation and incubated. The fibrinolytic activity of the ultrafiltrate was 10 times as great as that of the concentrate. 3) The ultrafiltrate of MAT was extracted in turn with petroleum ether, ether and hexane. The fibrinolytic activity of the petroleum ether and hexane extracts was higher than that of the ether extracts. These results suggest that MAT has a low polarity, low molecular weight, and lipid like substance (inducer of PA,IPA), which stimulates the Mpr to release PA.
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PMID:[Studies on fibrinolysis and ascites accumulation associated with peritonitis carcinomatosa--inducer of plasminogen activator (IPA) in malignant ascites tumor]. 294 4

Purified mouse T lymphocytes were separated into Lyt-2+ and Lyt-2- populations by the procedure of panning, in which a monoclonal rat anti-Lyt-2 antibody and dishes coated with affinity-purified mouse anti-rat Ig antibodies were used. The populations obtained were 95 to 99% pure as determined by immunofluorescence. Graded doses of these T cells were cultured with optimal mitogenic doses of concanavalin A and the 0 to 24 and 24 to 48-hr culture supernatants were collected. The dose-curve assays of the supernatants of Lyt-2+ and Lyt-2- cells showed comparable activity in interleukin 2 (IL 2) and T cell-replacing factor (TRF), assayed on antigen-stimulated culture of T-depleted spleen cells. Limiting dilution assays of IL 2-secreting precursor cells stimulated by Con A showed a high frequency of precursors in both populations, slightly higher among Lyt-2- cells. The supernatants also contained comparable levels of IPA (inducer of plasminogen activator production by the macrophages), MAF (macrophage-activating factor, assayed by induction of their cytolytic function), and MCGF (mast cells growth factor, assayed on a mast cell line). IPA and MAF were not produced with the same kinetics and in the same T cell concentration conditions as IL 2 and TRF. In contrast, interferon was principally produced by the Lyt-2+ cells.
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PMID:Positively selected Lyt-2+ and Lyt-2- mouse T lymphocytes are comparable, after Con A stimulation, in release of IL 2 and of lymphokines acting on B cells, macrophages, and mast cells, but differ in interferon production. 618 45

We have used the molecular dynamics (MD) simulation package AMBER4 to search the conformation of a peptide predicted as a leucine zipper motif for the human immunodeficiency virus type 1 integrase protein (HIV IN-LZM). The peptide is composed of 22 amino acid residues and its location is from Val 151 to Leu 172. The searching procedure also includes two known alpha-helices that served as positive controls--namely, a 22-residue GCN4-p1 (LZM) and a 20-residue poly (L-alanine) (PLA). A 21-residue peptide extracted from a cytochrome C crystal (CCC-t) with determined conformation as a beta-turn is also included as a negative control. At the beginning of the search, two starting conformations--namely, the standard right-handed alpha-helix and the fully stretched conformations--are generated for each peptide. Structures generated as standard alpha-helix are equilibrated at room temperature for 90 ps while structures generated as a fully stretched one are equilibrated at 600 K for 120 ps. The CCC-t and PLA helices are nearly destroyed from the beginning of equilibration. However, for both the HIV IN-LZM and the GCN4-p1 LZM structures, there is substantial helicity being retained throughout the entire course of equilibration. Although helix propagation profiles calculated indicate that both peptides possess about the same propensity to form an alpha-helix, the HIV IN-LZM helix appears to be more stable than the GCN4-p1 one as judged by a variety of analyses on both structures generated during the equilibration course. The fact that predicted HIV IN-LZM can exist as an alpha-helix is also supported by the results of high temperature equilibration run on the fully stretched structures generated. In this run, the RMS deviations between the backbone atoms of the structures with the lowest potential energy (PE) identified within every 2 ps and the structure with the lowest PE searched in the same course of simulation are calculated. For both the HIV IN-LZM and the GCN4-p1 LZM, these rms values decrease with the decrease of PE, which indicates that both structures are closer in conformations as their PEs are moved deeper into the PE well.
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PMID:Molecular dynamics simulation of a leucine zipper motif predicted for the integrase of human immunodeficiency virus type 1. 807 85

A 21-year-old male presented with melaena and signs of hemorrhagic shock. In the following days several episodes of hematochezia occurred requiring the transfusion of nine units of blood. Findings at gastroscopy were normal, at colonoscopy fresh blood was noted from the ileocecal valve. Angiography performed in a bleeding-free interval showed no abnormalities. At repeat angiography, bleeding (from a left lateral branch of the superior mesenteric artery) was provoked by instillation of plasminogen activator. Subsequently, hemostasis was achieved by superselective embolization using coils. At operation one week later, a polypoid tumor of 1 cm diameter was resected along with a 4 cm segment of adjacent jejunum (40 cm distal to the ligament of Treitz). Histologically, a jejunal varix with superficial ulceration was diagnosed.
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PMID:[Massive hemorrhage from jejunal varices]. 917 88

Data from recent prospective studies of hemostasis and thrombosis indicate that the plasma concentration of endogenous tissue-type plasminogen activator (tPA) is often elevated years in advance of a first arterial occlusion. Specifically, among healthy subjects with no prior cardiovasacular disease, the risk of future myocardial infarction and stroke appears to be three to four times higher among subjects with high baseline levels of tPA antigen as compared to subjects with lower levels. Whether this relationship represents activation of the endogenous fibrinolytic system in response to the presence of preclinical atherosclerosis or is a reflection of elevated concentrations of local plasminogen activator inhibitors is currently unresolved. However, cross-sectional data indicate that the plasma concentration of IPA antigen is related to several traditional atherosclerotic risk factors, including HDL cholesterol, findings that further support a direct relationship between endogenous IPA and vascular risk. In concert with data concerning the primary inhibitors of plasminogen activation, it has been hypothesizd that the endogenous fibrinolytic system varies within the general population such that certain individuals are prone to thrombosis, whereas others may be prone to hemorrhage. Thus, observations regarding fibrinolytic activation and inhibition raise the possibility that assessment of the intrinsic fibrinolytic system may prove useful in identifying individuals at increased risk for vascular thrombosis. In addition, available findings suggest that therapeutic agents capable of favorably shifting the net filerinolytic balance may provide a new strategy for cardiovascular disease prevention.
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PMID:Plasma Concentration of Endogenous Tissue Plasminogen Activator and the Occurrence of Future Cardiovascular Events. 1060 9

A 21-month retrospective review was completed at the Lucile Packard Children's Hospital to assess the experience of 22 infants and children who received alteplase for the clearance of occluded central venous access devices. After the first dose, 86% (n = 19) of the catheters cleared. Two additional catheters cleared with a second dose. With alteplase treatment, 95% (n = 21) of the catheters cleared. No adverse events were noted within 24 hours after the alteplase was received. Infusion of alteplase appeared to be safe and effective in restoring patency to occluded central venous access devices in infants and children.
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PMID:The use of alteplase for restoring patency to occluded central venous access devices in infants and children. 1511 55

Pulmonary embolism (PE) is an important cause of morbidity and mortality during pregnancy. A 21-year-old pregnant woman presented with chest pain and progressive shortness of breath at 35 weeks of gestation. Her respiratory rate was 26 breaths/min. Electrocardiography showed sinus tachycardia and nonspecific ST-T changes. Her plasma D-dimer level was elevated (1,325 ng/ml). Transthoracic echocardiography revealed enlargement of the right ventricle and a large, highly mobile thrombus in the right atrium moving during diastole into the right ventricle. Doppler ultrasonography of the lower extremities showed bilateral acute deep femoral vein thrombosis. Following the diagnosis of right heart thrombosis with massive PE, low-dose and prolonged infusion of tissue-type plasminogen activator (25 mg in three hours) was administered. Echocardiography performed six hours after thrombolysis showed a significant decrease in the right ventricular size and complete lysis of the thrombus in the right heart. Thrombosis risk panel studies showed factor V Leiden homozygote mutation. A live newborn was delivered by cesarean section at 37 weeks of gestation. No complications were seen during a 6-month follow-up.
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PMID:Successful treatment of massive pulmonary embolism in a pregnant woman, with low-dose, slow infusion of tissue plasminogen activator. 2021 40

Babies are frequently exposed to cerebral hypoxia and ischemia (H/I) during the perinatal period as a result of stroke, problems with delivery, or postdelivery respiratory management. The sole approved treatment for acute stroke is tissue type plasminogen activator. H/I impairs pial artery dilation (PAD) induced by hypercapnia and hypotension, the impairment aggravated by type plasminogen activator and attenuated by the plasminogen activator inhibitor-1-derived peptide EEIIMD. Mitogen-activated protein kinase (MAPK), a family of at least three kinases, ERK, p38, and JNK, is upregulated after H/I and ERK contribute to impaired cerebrovasodilation. This study determined the roles of p38 and JNK MAPK in the impairment of dilation post-H/I in pigs equipped with a closed cranial window and the relationship between alterations in MAPK isoforms and EEIIMD-mediated cerebrovascular protection. Cerebrospinal fluid-phosphorylated (activated) p38 MAPK, but not JNK MAPK, was increased after H/I, an effect potentiated by intravenous EEIIMD administered 1 h postinjury. PAD in response to hypercapnia and hypotension was blunted by H/I, but dilation was maintained by EEIIMD. PAD was further impaired by the p38 antagonist SB-203580 but unchanged by the JNK antagonist SP-600125. Isoproterenol-induced PAD was unchanged by H/I, EEIIMD, SB-203580, and SP-600125. These data indicate that postinjury treatment with EEIIMD attenuated impaired cerebrovasodilation post-H/I by upregulating p38 but not JNK. These data suggest that plasminogen activator inhibitor-1-based peptides and other approaches to upregulate p38 may offer a novel approach to increase the benefit-to-risk ratio of thrombolytic therapy for diverse central nervous system disorders associated with H/I.
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PMID:PAI-1-derived peptide EEIIMD prevents impairment of cerebrovasodilation by augmenting p38 MAPK upregulation after cerebral hypoxia/ischemia. 2043 43

A 21-year old female, recently diagnosed with osteosarcoma of right humerus, presented to the emergency with history of fever, productive cough, chest pain and progressive respiratory distress for six days. Initial investigations suggested pneumonia but she did not respond to parenteral antibiotics. CT pulmonary angiogram revealed bilateral pulmonary artery embolism. Thrombolysis was performed using alteplase, which failed to improve the clinical condition. In view of underlying malignancy, a possibility of tumour-embolism was considered and she was started on chemotherapy for osteosarcoma. There was dramatic improvement in her respiratory symptoms after the first chemotherapy cycle, along with radiological resolution of the embolism. This case highlights the importance of suspecting tumour embolism in a known case of malignancy with respiratory distress.
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PMID:Treatment of Pulmonary Embolism with Chemotherapy in a Case of Newly Diagnosed Osteosarcoma. 3129 47