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)

Tissue-type plasminogen activator, von Willebrand factor, and plasminogen-activator inhibitor type 1 plasma levels were measured at first consultation in 85 consecutive patients infected with human immunodeficiency virus. Patients were assigned to three groups according to clinical status: mild disease group, intermediate group, and acquired immunodeficiency syndrome group. Significant differences were found in von Willebrand factor, tissue-type plasminogen activator, and plasminogen-activator inhibitor type 1 plasma levels among the three groups: severe clinical status was associated with higher von Willebrand factor, tissue-type plasminogen activator, and plasminogen-activator inhibitor type 1 plasma levels. Significant correlations were found among these three parameters, such known biologic prognostic indicators of human immunodeficiency virus infection as IgA, anti-p24 antibodies, p24 antigenemia, CD4+ lymphocytes, beta 2-microglobulin, and the clinical status. The prognostic relevance of plasma von Willebrand factor and tissue-type plasminogen activator levels at the time of entry into the study was then investigated in a cohort of 65 of the 85 patients who had follow-up during a median period of 22 months. The median survival time for all patients was 39 months after the first consultation. A plasma von Willebrand factor level greater than 200% of the control value had a positive predictive value of 86% for determining nonsurvivors; the median survival time for such patients was 9 months after the first consultation. A positive predictive value of 100% in recognizing nonsurvivors was found for tissue-type plasminogen factor plasma levels greater than 20 ng/ml; the median survival time for these patients was 2 months after the first consultation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:von Willebrand factor antigen, tissue-type plasminogen activator antigen, and risk of death in human immunodeficiency virus 1-related clinical disease: independent prognostic relevance of tissue-type plasminogen activator. 151 88

We have observed that proteins, such as human tissue-type plasminogen activator, pro-urokinase or gp41 of human immunodeficiency virus, which have a high content of rare codons in their respective genes, are not readily expressed in Escherichia coli. Furthermore induction of these heterologous genes leads to growth inhibition and plasmid instability. Supplementation with tRNA(AGA/AGG(Arg)) by cotransfection with the dnaY gene, which supplies this minor tRNA, resulted in high-level production with greatly improved cell viability and plasmid stability.
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PMID:High-level expression of recombinant genes in Escherichia coli is dependent on the availability of the dnaY gene product. 251 92

Many eukaryotic DNA sequences, especially lenti-retrovirus proviral genomes and their env genes, are unstable when cloned in high-copy-number plasmids in Escherichia coli. Stability can be increased by the use of low-copy-number vectors, although plasmid yields are low. Vectors are described here that contain the intermediate-copy-number P15A ori for cloning, stable propagation and higher-yield production of plasmid DNA in E. coli, and the f1 ori for propagation as single-stranded phage. These vectors also have the capacity to direct high-yield production of protein in mammalian cells, and the option of incorporation into and expression via a T7 promoter in vaccinia virus. The SR alpha promoter, encephalomyocarditis (EMC) virus untranslated leader sequence, and poly(A) signal sequence serve as a high-yield mammalian cell expression cassette without the requirement for mRNA capping. A polyhistidine sequence is available at the 3' end of the cassette to facilitate chromatographic purification of protein. neo and gpt genes were included in some vectors to serve as selectable markers, and the dhfr gene was included in one to achieve gene amplification in mammalian cells. Dicistronic mRNAs can be generated by insertion of coding sequences up and downstream from the EMC leader. The utility of these vectors was shown through expression of feline immunodeficiency virus (FIV) Env protein, in conjunction with the tissue plasminogen activator (tPA) leader sequence.
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PMID:Mammalian cell/vaccinia virus expression vectors with increased stability of retroviral sequences in Escherichia coli: production of feline immunodeficiency virus envelope protein. 787 88

Widespread digital ischemic changes and gangrene of the hands and feet is an uncommon but dramatic presentation in patients with human immunodeficiency virus (HIV) infection. We describe a patient in whom these clinical findings were associated with elevated serum endothelin levels. Because endothelin may affect the fibrinolytic system, we elected to treat with tissue plasminogen activator (tPA), which resulted in salvage of tissue of the fingers and toes. Patients with HIV infection with widespread ischemic necrosis and gangrene may require treatment with corticosteroids (in the event of possible vasculitis), thrombolytic agents (for the thrombotic component), or both, unless there are contraindications to either.
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PMID:Digital necrosis in acquired immune deficiency syndrome vasculopathy treated with recombinant tissue plasminogen activator. 937 95

A synthetic gene consisting of the reverse transcriptase (RT) and integrase (IN) domains of human immunodeficiency virus type 1 (HIV-1) pol was constructed using codons most frequently used in humans. The humanized pol gave dramatically improved levels of Rev-independent, in vitro protein production in mammalian cells and elicited much stronger cellular immunity in rodents than did virus-derived gene. Specifically, BALB/c mice were immunized with plasmids and/or recombinant vaccinia virus constructs expressing the synthetic gene. High frequencies of Pol-specific T lymphocytes were detected in these animals by the gamma interferon enzyme-linked immunospot assay against pools of short overlapping peptides. Characterization of the stimulatory peptides from these pools indicates that the optimized gene constructs are able to effectively activate both CD4+ and CD8+ T cells. Immunization of rhesus macaques with DNA vaccines expressing the humanized pol coupled to a human tissue plasminogen activator leader sequence led to pronounced in vitro cytotoxic T-lymphocyte killing activities and enhanced levels of circulating Pol-specific T cells, comparable to those observed in HIV-1-infected human subjects. Thus, optimizing the immunogenic properties of HIV-1 Pol at the level of the gene sequence validates it as an antigen and provides an important step toward the construction of a potent pol-based HIV-1 vaccine component.
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PMID:Vaccine-induced immune responses in rodents and nonhuman primates by use of a humanized human immunodeficiency virus type 1 pol gene. 1173 84

We examined the influence of dose and method of antigen delivery on the dynamics and durability of T-cell responses to candidate human immunodeficiency virus (HIV) vaccines. Codon-optimized sequences from the HIV gag gene were inserted into alternative DNA vaccine vectors to express the coding sequence with or without the tissue plasminogen activator leader sequence. We delivered the vaccines by intramuscular injection as plasmid DNA without adjuvant or as plasmid DNA formulated with a novel block copolymer adjuvant (CRL8623) and then monitored the ensuing T-cell responses by using a gamma interferon enzyme-linked immunospot assay. We demonstrated persistence of the cell-mediated immune (CMI) response in rhesus macaques for at least 18 months following a four-dose vaccination regimen. The plasmid vaccine, with or without CRL8623, was immunogenic in macaques; however, the form coadministered with adjuvant exhibited improved T-cell responses, with a bias toward more antigen-specific CD8(+) T cells. Finally, we examined the fine specificity of the T-cell response to the gag vaccines by testing the response of 23 vaccinated macaques to individual Gag 20-mer peptides. Collectively, the monkeys responded to 25 epitopes, and, on average, each monkey recognized a minimum of 2.7 epitopes. The results indicate that a broad and durable CMI response to HIV DNA vaccines can be induced in a relevant nonhuman primate model.
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PMID:Sustained peptide-specific gamma interferon T-cell response in rhesus macaques immunized with human immunodeficiency virus gag DNA vaccines. 1220 82

The endothelium participates in haemostasis, inflammation, blood pressure regulation and other physiological systems. Consequently, endothelial dysfunction has been related to hypertension, thrombosis and atherosclerosis. Both von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA) are synthesized by the endothelium and their plasma levels increased during endothelium activation or injury. So far, they are well-known markers of endothelial cell function. Many circumstances activate or damage the endothelium, such as viruses, bacterium and inflammation. Circulating vWF and t-PA were studied in 92 unselected human immunodeficiency virus-1 (HIV-1)-infected patients [27 patients with and 65 patients without acquired immunodeficiency syndrome (AIDS)] and correlated with plasma levels of pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-6), viral load, CD4 T-cell count and infectious status. HIV-1-infected patients had significantly higher plasma levels of vWF (152 versus 90%), tumour necrosis factor-alpha (31.3 versus 9.0 pg/ml) and interleukin-6 (3.5 versus 1.9 pg/ml) but not t-PA (5.9 versus 4.2 ng/ml) than the control group. These two endothelial markers correlated significantly with viral load and interleukin-6 levels in HIV-1-infected patients. The highest levels of vWF and t-PA were found in patients with AIDS. In conclusion, endothelial cell perturbation is present in HIV infection and may be a consequence of different mechanisms such as viral load, cytokines and advanced diseases.
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PMID:Viral load and disease progression as responsible for endothelial activation and/or injury in human immunodeficiency virus-1-infected patients. 1254 23

Hepatic veno-occlusive disease (HVOD) following bone marrow transplantation is potentially fatal. Criteria for diagnosis and starting treatment are mainly based on adult studies. Recombinant tissue plasminogen activator (rtPA) has been used with variable success. rtPA and heparin were given to 12 children (nine with immunodeficiency, two malignancy, one thalassaemia) with moderate to severe HVOD. Of the 12, 10 responded with a fall in bilirubin concentration; eight survived with complete resolution of HVOD. Four of the five patients with associated multiorgan failure (MOF) died despite rtPA treatment. One child suffered significant, and one minor, bleeding during rtPA treatment. A scoring system for quantifying the severity of HVOD in children is proposed, incorporating the criteria used to diagnose HVOD, risk factors for its development and also parameters reflective of the patient's general condition. This will facilitate early diagnosis and management of those cases which, if not treated promptly, are likely to deteriorate with an adverse outcome. Our experience suggests rtPA and heparin are an effective treatment for HVOD in children, with relatively little toxicity provided therapy is started before MOF develops.
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PMID:Recombinant tissue plasminogen activator for treatment of hepatic veno-occlusive disease following bone marrow transplantation in children: effectiveness and a scoring system for initiating treatment. 1269 27

In certain cell systems, exchange of the human immunodeficiency virus (HIV) Env signal peptide (SP) sequence with that of heterologous SPs has been shown to increase gp120 transport and secretion. Here we demonstrate that exchange of the HIV-Env-SP with those from erythropoietin or tissue plasminogen activator in the proviral context does not increase wild-type membrane-bound Env expression or incorporation into released virions. In fact, virion infectivity was decreased. These infectivity decreases were largely due to effects on Env transport and/or function and only to a minor extent to cis effects as a result of the sequence exchanges themselves. Thus, in fact, it is not advantageous to employ heterologous SPs to achieve high-level expression of functional cell surface membrane- or virion-associated HIV-Env.
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PMID:Effects of signal peptide exchange on HIV-1 glycoprotein expression and viral infectivity in mammalian cells. 1677 98

Blood products are those biologicals derived from plasma or obtained by recombinant technologies. This overview covers the characteristics and classification of plasma proteins, the current status of products (albumin, immunoglobulins, coagulation factors and microcontent proteins), as well as the likely trends in the near future. Human serum albumin is one of the earliest, safest and most widely used proteins in the pharmaceutical field. The approval and development of high-purity plasma albumin, recombinant human albumin and HSA fusion proteins provide a favorable prospect for the therapeutic protein. Normal immunoglobulin contains antibodies to all the micro-organisms prevalent in the donor population. The IMIG is relatively simple to prepare and use, and the side effects are acceptable; IVIG is used mainly to treat patients with primary immunodeficiency syndromes; SCIG preparations can be used in selecting suitable patients for home therapy and have occurred fewer adverse systemic reactions; specific immunoglobulins contain concentrations of antibody to an individual organism or toxin at a higher titer than normal immunoglobulin and can not be replaced in clinical use. The plasma-derived or recombinant coagulation factors are used to treat the patients with congenital or acquired factor deficiency. The products such as Fibrinogen, FVII, FVIII, von Willebrand complex, FIX/PCC, FXI, FXIII and so on, have been widely used and proved to be effective. The development of recombinant FVIIa is now as a good bypassing product to haemophilia with inhibitors. The Fibrinogen and thrombin play a very important role in surgery hemostasis. Moreover, microcontent proteins including protein C, antithrombin, alpha 1-AT, tPA have been licensed and used in clinical treatment; a number of other small field proteins are under produced research or pre-clinical investment. The ongoing development of new recombinant plasma proteins is providing alternatives for patients, but the distinct position and the potential impact of plasma-derived preparations are unique, furthermore the development of new plasma protein is still a hot spot in global pharmaceutics. Nowadays, a relative difference exists in the development of blood products between our nation and developed countries, so the domestic manufacturers are faced with chances and challenges.
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PMID:[Current status and trends in blood biologicals]. 2184 40


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