Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of plasminogen activators (PA) and their inhibitors (PAI) in the rat cell lines: HTC and L2 was studied. HTC plasminogen activator inhibitor type 1 (PAI-1) production was stimulated by dexamethasone, serum factors and insulin; that of tissue-type plasminogen activator (tPA) by cAMP raising agents. Retinoic acid, butyrate, phorbol ester and endotoxin did not affect net PA/PAI activity elaborated by HTC. L2 cells produced tPA, which production was stimulated by retinoic acid, phorbol myristate acetate, butyrate and cAMP; serum factors blunted their response, whereas in the synthetic serum substituting medium Ultraculture and with cocktail Ultroser the action of tPA stimulators was enhanced.
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PMID:Regulation of plasminogen activation in rat cell lines. 128 21

Less than a decade ago, the use of continuous mammalian cell lines for the production of cloned proteins was considered strictly a research tool. At that time, few thought it possible to allay the many safety concerns associated with transformed cells. It soon became clear that mammalian expression systems had numerous advantages over bacteria for production of therapeutic proteins, initiating a multidisciplinary effort to address these concerns in a thorough and reliable manner. The success of these efforts is exemplified by the emergence of product molecules into the market. Today, there are seven recombinant human therapeutics that have received FDA approval. Almost half of them (OKT3, t-PA, and EPO) are produced in mammalian cells, with the remainder produced in bacteria (insulin, growth hormone, and alpha-interferon) or yeast (hepatitis vaccine). At least a dozen more recombinant cell culture products are in advanced human clinical trials. With the accumulation of data and experience, continuous mammalian cell lines will no doubt be the preferred hosts for many future products of biotechnology.
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PMID:Downstream processing of proteins from mammalian cells. 136 66

Lipoprotein(a) (Lp(a)) has been established as an important independent risk factor for the development of cardiovascular disease. Apolipoprotein(a), together with apo B-100 the apolipoprotein of Lp(a), is homologeous to plasminogen but lacks fibrinolytic capacity and appeared to interfere with fibrinolysis in in vitro and ex vivo experiments. We determined the correlations between Lp(a) and other blood lipids (serum cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), coagulation parameters (fibrinogen, factor VII, factor VIII:C fibrin monomers, thrombin-antithrombin III) and fibrinolysis parameters (tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and D-dimer) in 54 patients with essential hypertension, in 65 non-insulin-dependent diabetic patients and in 116 insulin-regulated diabetic patients. Signs of activated coagulation and increased reactive fibrinolysis were found in all three patient groups. In the hypertensive patients, Lp(a) was significantly correlated with LDL-cholesterol (r = 0.25, P = 0.04) and triglycerides (r = -0.30, P = 0.03), while in insulin-regulated diabetics, Lp(a) was also correlated with LDL-cholesterol (r = 0.20, P = 0.03). In the hypertensive patients and both diabetic groups there was no correlation of Lp(a) with coagulation or fibrinolysis parameters. These data show that Lp(a) concentrations are not related to coagulation or fibrinolysis parameters in hypertensive or diabetic patients and confirm the presence of an activated coagulation system in these patient groups.
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PMID:Low order correlations of lipoprotein(a) with other blood lipids and with coagulation and fibrinolysis parameters in hypertensive and diabetic patients. 138 33

Beside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of insulin treatment on the balance between tissue plasminogen activator and plasminogen activator inhibitor-1 in type 2 diabetic patients. 144 Apr 87

Forty-five patients who had been subjected to jejuno-ileal bypass (JIB) surgery for morbid obesity and 10 obese nonsurgery subjects were studied. The former group was examined 14 to 20 years after surgery, and was found to have lower mean plasminogen activator inhibitor type 1 (PAI-1) activity (8.4 v 32 U/mL, P < .001), tissue plasminogen activator (tPA) antigen concentrations (7.2 v 12 micrograms/L, P < .01), body mass index (BMI), and fasting plasma insulin, triglyceride, and cholesterol levels. The PAI-1 levels were correlated with BMI, waist to hip ratio, and insulin, triglyceride, and cholesterol levels. Thus, previously obese subjects have normal PAI levels 14 to 20 years after treatment with JIB surgery, in contrast to the high PAI-1 levels in nonsurgery obese subjects.
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PMID:Normal plasminogen activator inhibitor levels at long-term follow-up after jejuno-ileal bypass surgery in morbidly obese individuals. 146 Nov 44

Testicular peritubular cells produce a paracrine factor termed PModS that has dramatic effects on Sertoli cell function in vitro. The current study was designed to examine the actions of PModS and hormones on Sertoli cell aromatase activity and plasminogen activator production at various stages of pubertal development. Sertoli cells were isolated from 10-, 20-, and 35-day-old rats (ages correspond to prepubertal, midpubertal, and late-pubertal stages of development). Aromatase activity was found to be high and hormone-responsive in prepubertal Sertoli cells and to decline and be nonresponsive to hormones in late-pubertal Sertoli cells. FSH was the only hormone found to influence aromatase activity and estrogen production. PModS alone was not found to affect aromatase activity at any of the developmental stages examined. Interestingly, PModS was found to suppress the ability of FSH to stimulate aromatase activity and estrogen production in midpubertal Sertoli cells. Results imply that PModS may promote Sertoli cell differentiation to a more adult stage of development that is less responsive to FSH in stimulating aromatase activity. In contrast to aromatase activity, plasminogen activator production was found to increase during pubertal development. Production of Sertoli cell tissue-type plasminogen activator (tPa) was stimulated by FSH at each of the developmental stages examined, whereas production of urokinase-type plasminogen activator (uPa) was influenced by FSH only in prepubertal Sertoli cells. Insulin also stimulated uPa and tPa production by prepubertal Sertoli cells, and retinol significantly suppressed uPa production and the ability of FSH to stimulate tPa production by midpubertal Sertoli cells.
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PMID:Developmental regulation of Sertoli cell aromatase activity and plasminogen activator production by hormones, retinoids and the testicular paracrine factor, PModS. 157 55

The mechanism underlying diurnal variations in PAI-1 as well as the cellular origin of PAI-1 in subjects with high PAI-1 levels are unknown. We evaluated diurnal changes (8:00 am vs 4:00 pm) in PAI-1 (functional and immunological assays), t-PA Ag and t-PA/PAI-1 complex levels in controls and subjects with high PAI-1 levels. Three test groups were recruited among obese hyperinsulinemic subjects, emergency care unit patients with inflammatory syndrome or infection and pregnant women. The classical afternoon decrease of PAI-1 level was observed in controls and obese subjects but its amplitude was greater in the latter. The decrease in t-PA Ag and t-PA/PAI-1 complex levels was the same in controls and in obese. As, in previous studies, elevated PAI-1 levels have been correlated with insulin resistance and a decrease in insulin sensibility has been described in the early morning, it is proposed that this "dawn phenomenon" could be implicated in the circadian variations of PAI-1 in controls and could be amplified in obese subjects. Great variability in PAI-1, t-PA Ag or t-PA/PAI-1 complex levels was observed in patients with acute inflammatory syndrome or infection for whom classical biorhythms are suppressed. No diurnal changes in PAI-1 and other fibrinolytic parameters were observed in patients with inflammatory syndrome or in pregnant women suggesting that other sources and/or other regulatory mechanisms of PAI-1 production are involved.
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PMID:Daytime fluctuations of plasminogen activator inhibitor 1 (PAI-1) in populations with high PAI-1 levels. 161 88

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. 162 64

Seborrheic keratoses were investigated by means of histo- and biochemical techniques in order to define the epidermal differentiation and proliferation of this most common epithelial tumor in adults. The following markers have been used in our study: cytokeratins, epidermal proteins binding zinc, insulin receptors, tissue plasminogen activator (tPA), as well as calmodulin (immunohistochemical and quantitative evaluation). Immunohistochemical investigation of seborrheic keratoses revealed a decreased tPA expression; their epidermal concentration of calmodulin was doubled. The differentiation markers failed to show any significant deviation from normal skin. Thus, seborrheic keratoses are associated with normal epidermal differentiation in spite of morphogenic alterations. Pathogenetically, we have to consider epidermaldermal interactions.
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PMID:[Seborrheic keratoses. Intact epidermal differentiation despite disordered morphogenesis]. 169 26

Rhabdoid tumor of kidney (RTK) is a rare, highly malignant childhood neoplasm of uncertain histogenesis. Several recent studies have described considerable histochemical heterogeneity among cases of RTK, with confusing combinations of epithelial, mesenchymal, myogenous, and neuroepithelial markers in some tumors. The present study characterizes the histology, ultrastructure, histochemistry, cytogenetics, and oncogene expression in a cell line derived from RTK. The surgical specimen, nude mouse xenograft, and cell cultures demonstrated characteristic intermediate filament whorls by electron microscopy and expressed vimentin (diffusely) and cytokeratin (focally, in hyaline cytoplasmic inclusions) without detectable desmin, Thy-1, or epithelial membrane antigen. S-100 protein was absent in the surgical specimen and heterotransplant, and was seen very weakly and focally in the cell cultures. Light microscopic features of cultures were unchanged by several compounds (tissue plasminogen activator, nerve growth factor, cyclic adenosine monophosphate) which induce differentiation of some other pediatric neoplasms. The growth factor requirements of RTK cultures indicate a cell with mesenchymal features. Insulin-like growth factor-2 mRNA was detected in the RTK and in three Wilms' tumors also studied. Unlike most Wilms' tumors, RTK expresses the c-myc rather than the N-myc oncogene.
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PMID:Characterization of a cell line derived from rhabdoid tumor of kidney. 170 6


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