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T Quertermous

Publications and source records attributed to T Quertermous.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cooperative interaction of GATA-2 and AP1 regulates transcription of the endothelin-1 gene.

Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide initially characterized as a product of endothelial cells. Reporter gene transfection experiments have indicated that a GATA site and an AP1 site are essential for ET-1 promoter function in endothelial cells, and GATA-2 appears to be the active GATA factor which regulates ET-1 expression. To look for interactions between AP1 and GATA-2, transactivation experiments were performed with expression vectors encoding c-Jun, c-Fos, and GATA-2. Cooperativity between the AP1 complex and GATA-2 was observed as a synergistic increase in transcriptional activity of the ET-1 reporter plasmid. In addition, AP1 was able to potentiate the action of GATA-2 on reporter constructs lacking a functional AP1 site. In a similar fashion, GATA-2 was able to potentiate the action of AP1 despite deletion of the GATA site. Experiments with GATA-1 and GATA-3 expression vectors provided evidence that this capacity to interact with AP1 may be a characteristic of all GATA family members. Biochemical evidence for AP1-GATA interaction was provided by immunoprecipitation experiments. A GATA-2-specific antiserum was shown to immunoprecipitate in vitro-synthesized Jun and Fos protein from reticulocyte lysate. Also, antisera directed against Jun and Fos were able to immunoprecipitate from nuclear extracts a GATA-binding protein, indicating the association of AP1 and GATA proteins in vivo.

Base Sequence↗
PubMed1995

Regional and maturation-associated expression of endothelin 2 in rat gastrointestinal tract.

Endothelin 2 (ET2), also referred to as vasoactive intestinal contractor peptide, is a member of a family of vasoactive peptides. ET2 is a potent constrictor of intestinal smooth muscle, and the mRNA that encodes it has been detected in murine intestinal extracts. To further investigate the potential physiological roles of ET2, we characterized the cellular distribution of ET2 gene expression in adult rat gastrointestinal tract. Using an RNAse protection assay, an overall proximal to distal gradient of increasing ET2 gene expression was observed from stomach to colon. In situ hybridization studies confirmed this finding and demonstrated ET2 mRNA localized in lamina propria stromal cells. Moreover, ET2 gene expression in stromal cells increased from crypt to villous tip. The results demonstrate that ET2 is produced by stromal cells in villi throughout the intestine. Increased ET2 gene expression at the villous tip is associated with more mature overlying epithelial cells, suggesting a possible role for this vasoactive peptide in intestinal epithelial differentiation or secretory activity.

Animals↗
PubMed1994

Cloning and characterization of a basic helix-loop-helix protein expressed in early mesoderm and the developing somites.

Basic helix-loop-helix (bHLH) heterodimer protein complexes regulate transcription of genes during the processes of differentiation and development. To study the molecular basis of early mesodermal differentiation, we sought to identify bHLH proteins from cells of mesodermal origin. By using an interaction cloning strategy with a radiolabled recombinant bHLH protein, E12, a clone encoding a potential heterodimer partner was isolated from an endothelial cell library. This gene (bHLH-EC2) is most homologous to Twist but shares similarity within the bHLH domain with TAL1 and other members of this family. bHLH-EC2 is expressed in cultured endothelial cells and in embryonic stem cell, erythroleukemia, and muscle cell lines in a differentiation-dependent manner. In situ hybridization studies of mouse embryos reveal that bHLH-EC2 is expressed throughout the primitive mesoderm as early as 7.5 days postcoitum. Expression then becomes restricted to the paraxial mesoderm and to the dermamyotome of the developing somite. Expression of bHLH-EC2 in cells destined to become myoblasts thus predates expression of myogenic bHLH factors. bHLH-EC2 is expressed in early endothelial and hematopoietic cells in vivo, as shown by RNA studies of embryonic yolk sac and cultured cells derived from yolk sac explants. These findings suggest that bHLH-EC2 plays a role in the development of multiple cell types derived from the primitive mesoderm.

Amino Acid Sequence↗
PubMed1994

The immunoreactive region in a novel autoantigen contains a nuclear localization sequence.

Antibodies in the serum of patients with autoimmune diseases have been used to identify human autoantigens. Because autoantibodies often recognize active sites within corresponding protein antigens, autoantibodies have facilitated the functional characterization of these polypeptides. In the present study, serum from a patient with Sjögren's syndrome was used to identify a novel autoantigen which was designated Ge-1. Using the patient's serum, a 4.8-kb cDNA encoding Ge-1 was identified. Fragments of the cDNA were ligated into prokaryotic expression vectors, expressed in Escherichia coli, and used to produce recombinant Ge-1 fusion proteins. Fusion proteins containing different portions of Ge-1 were used to identify a 58 amino acid immunoreactive region within the protein. This immunoreactive region contained the protein's putative nuclear localization sequence (NLS). To demonstrate that the immunoreactive region was capable of functioning as a NLS, a eukaryotic expression plasmid was constructed to encode the immunoreactive region fused to the cytoplasmic protein, chicken muscle pyruvate kinase. After transfection of this plasmid into COS-1 cells, the fusion protein was detected in the nucleus. The presence of the NLS motif within the immunoreactive region of Ge-1 and other nuclear autoantigens suggests that the NLS may be a target of human autoantibodies.

Amino Acid Sequence↗
PubMed1994

Pulmonary hypoxia increases endothelin-1 gene expression in sheep.

The hypoxic pulmonary vasoconstrictor response (HPVR) is a physiologic mechanism for directing pulmonary blood flow to nonhypoxic regions of the lung. The mechanism of this response remains unclear. To investigate the role of endothelin-1 (ET-1), a potent vasoconstrictor produced by vascular endothelium, in HPVR an in vivo model of alveolar hypoxia was developed. When one lung in an anesthetized sheep was made hypoxic, the static ET-1 mRNA levels in lung tissue increased in proportion to the observed decrease in pulmonary blood flow (Qp) to that lung. With reversal of hypoxia, Qp and ET-1 levels returned to baseline. This relationship between alveolar hypoxia and ET-1 mRNA levels suggests a role for ET-1 in the local pulmonary response to hypoxia.

Animals↗
PubMed1994

Cosegregation of the endothelin-3 locus with blood pressure and relative heart weight in inbred Dahl rats.

OBJECTIVE: To determine whether the endothelin-1 or endothelin-3 genes are genetically linked with blood pressure and relative heart weight in segregating rat populations, in the context of an elevated dietary sodium chloride intake. METHODS: Endothelin-1 and endothelin-3 genotypes of rats in segregating populations, derived from crosses of Dahl salt-sensitive (SS/Jr) rats with contrasting inbred strains, including Lewis rats, spontaneously hypertensive rats and Dahl salt-resistant (SR/Jr) rats, were determined using restriction fragment length polymorphisms. Segregating populations were fed a high (8%)-sodium chloride diet. Linkage of genotype with blood pressure or relative heart weight was determined by analysis of variance. Chromosomal location of the rat endothelin-3 gene was determined by genotyping a panel of recombinant inbred strains. RESULTS: Two alleles for the endothelin-1 gene and three alleles for the endothelin-3 gene were identified. The endothelin-1 locus did not cosegregate with blood pressure or relative heart weight. The endothelin-3 locus cosegregated with blood pressure and relative heart weight in an SS/Jr x F1 (SS/Jr x SR/Jr) population, but not in populations containing a higher percentage of genes from the SR/Jr strain. The endothelin-3 and seminal vesicle protein-1 loci were linked and located on rat chromosome 3. CONCLUSION: The endothelin-3 gene is, or is linked to, a locus on chromosome 3 that regulates blood pressure and relative heart weight in inbred Dahl rats, and these effects were strongly dependent on the genetic background.

Animals↗
PubMed1993

Effect of heavy chain signal peptide mutations and NH2-terminal chain length on binding of anti-digoxin antibodies.

In certain instances, antibody variable region mutations outside of the antigen-combining site influence antigen binding. We reported previously that a heavy chain mutation (Ser-94-->Arg) decreased binding of the anti-digoxin antibody 40-150, whereas an additional signal peptide mutation at the -2 position (Gln-->Pro) causing NH2-terminal 2-residue truncation partially restored binding. To assess the combined effects on binding of two seemingly distant mutations, we constructed signal peptide mutations and NH2-terminal deletions in the presence of Ser-94 and Arg-94. Deletions of one to three amino acids had little effect on binding for Ser-94 mutants, whereas 2-residue truncations produced directly or by signal peptide mutation increased affinity approximately 40-fold for Arg-94 mutants. These observations are consistent with the reported computer-generated model of antibody 40-150. Introduction of Pro at the signal peptide -3 position in 40-150 resulted in cleavage at alternative sites, with varying effects on affinity. Introduction of Pro at -2 into the anti-digoxin antibody 26-10 resulted, unexpectedly, in expression of heavy chains with 3 extra NH2-terminal residues, causing an approximately 100-fold reduction in affinity. Thus, both extensions and deletions of the heavy chain amino terminus can enhance or reduce antigen binding, depending on the structural context of specific antigen combining sites.

Amino Acid Sequence↗
PubMed1993

Structural organization and chromosomal assignment of the gene encoding the human heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently identified, potent smooth muscle cell mitogen of macrophage origin. It is expressed in a highly regulated fashion in vascular endothelial and smooth muscle cells, indicating a potentially important role for this gene in atherosclerosis. In addition, the HB-EGF precursor has recently been found to function as a receptor for diphtheria toxin. Using an HB-EGF cDNA probe, we cloned the human gene encoding HB-EGF. The HB-EGF gene contains six exons and five intervening sequences spanning 14 kb of DNA. By primer extension and S1 nuclease analysis, we located a major transcription start site (corresponding to an A residue) 14 bp beyond the 5' end of the HB-EGF cDNA. There were no TATAAA or CCAAT consensus sequences upstream of the transcription start site. The density of primer extension bands generated by RNA from endothelial cells treated with tumor necrosis factor-alpha (TNF-alpha) was 10 times higher than that of bands generated by the control, indicating that TNF-alpha increased the level of HB-EGF mRNA. Using transient reporter gene transfection experiments, we show that 2.0 kb of HB-EGF 5'-flanking sequence has promoter activity in bovine aortic endothelial cells. By analysis of DNA isolated from human-mouse somatic hybrid cell lines, we assign the HB-EGF gene to chromosome 5. By functional study, chromosome 5 has been associated with diphtheria toxin susceptibility.

Amino Acid Sequence↗
PubMed1993

High-level expression of antibody-plasminogen activator fusion proteins in hybridoma cells.

We show that the mouse gamma 2b heavy chain or human beta-globin 3' untranslated region can greatly enhance protein expression in myeloma cells transfected by genes coding for antibody-plasminogen activator fusion proteins. Expression plasmids were constructed containing a cloned genomic heavy chain variable region from fibrin-specific monoclonal antibody 59D8, a cloned genomic constant region of the mouse gamma 2b heavy chain, and DNA sequence coding for either tissue-type plasminogen activator (tPA) or a segment of urokinase (UK) and their respective 3' untranslated sequences. Cell lines transfected with these constructs, pSVtPA (tPA) and pSVUKG(UK), produced extremely low levels of mRNA and protein (0.008-0.06 micrograms/ml) in comparison with the parental 59D8 myeloma cell line (7.6-10 micrograms/ml). In vitro nuclear run-off analysis indicated that the low steady-state levels of mRNA encoded by pSVUKG(UK) did not result from a lower rate of transcription of the transfected gene (relative to the rate of transcription of the endogenous heavy chain gene in the 59D8 parent cells). In an attempt to increase protein secretion, we assembled the expression plasmids pSVtPA(Ig), pSVUKG(Ig), and pSVUKG(beta), in which the 3' untranslated region of the mouse gamma 2b heavy chain or human beta-globin gene was substituted for the 3' untranslated region of the plasminogen activator gene. Analysis of supernatant media from cell lines transfected with these constructs showed an increase in recombinant protein secretion of 68 to 100 fold in comparison with that from cell lines transfected with pSVtPA(tPA) or pSVUKG(UK).

Amino Acid Sequence↗
PubMed1992

Induction of heparin-binding epidermal growth factor-like growth factor mRNA by phorbol ester and angiotensin II in rat aortic smooth muscle cells.

To determine whether the gene encoding the recently identified heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent smooth muscle cell (SMC) mitogen of macrophage origin, is transcribed and regulated in vascular SMC, we isolated cDNA clones encoding rat HB-EGF from a macrophage library. Using the rat HB-EGF cDNA as a probe for RNA blot analysis, we detected low levels of HB-EGF mRNA in rat aortic SMC in culture. However, 20 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) and 10(-6) M angiotensin II (AII) induced a marked increase in HB-EGF mRNA levels in rat aortic SMC (11- and 4.6-fold, respectively) that was both dose- and time-dependent. In response to TPA and AII, HB-EGF mRNA levels increased rapidly, peaked at 2 h, and returned to base line at 7 h. This effect of AII on HB-EGF induction was specific, as evidenced by the fact that it could be completely blocked by the AII antagonist saralasin. This is the first demonstration that HB-EGF is transcribed and regulated in SMC. The inducible transcription of this potent SMC mitogen gene in vascular SMC suggests that HB-EGF may have an important autocrine role in the proliferation of SMC in vascular diseases such as atherosclerosis and hypertension.

Amino Acid Sequence↗
PubMed1992

Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase.

Nitric oxide, which accounts for the biological activity of endothelium-derived relaxing factor (EDRF), is synthesized in endothelial cells from L-arginine by nitric oxide synthase (NOS). We report here the cloning and functional expression of a cDNA encoding human endothelial NOS. Oligonucleotides corresponding to amino acid sequences shared by cytochrome P450 reductase and the recently identified brain NOS were synthesized to amplify a partial cDNA encoding a bovine endothelial cell NOS-related protein. This partial cDNA was used to isolate a cDNA encoding a human vascular endothelial NOS. The translated human protein is 1294 amino acids long and shares 52% of its amino acid sequence with brain NOS. Using RNA blot hybridization, abundant endothelial NOS mRNA was detected in unstimulated human umbilical vein endothelial cells. To determine the functional activity of the endothelial protein, we ligated the cDNA into an expression vector and transfected it into NIH3T3 cells. Cells expressing this cDNA contained abundant NADPH diaphorase activity, a histochemical marker for NOS. In co-culture assays, nitric oxide production by transfected cells increased guanylate cyclase activity in reporter rat fetal lung fibroblasts. In addition, NOS-catalyzed conversion of arginine to citrulline in transfected cells was significantly increased by A23187, a calcium ionophore. Isolation of a cDNA encoding a calcium-regulated, constitutively expressed human endothelial NOS, capable of producing EDRF in blood vessels, will accelerate the characterization of the role of this enzyme in normal and abnormal endothelial regulation of vascular tone.

3T3 Cells↗
PubMed1992

Tumor necrosis factor increases transcription of the heparin-binding epidermal growth factor-like growth factor gene in vascular endothelial cells.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently identified, potent vascular smooth muscle cell (SMC) mitogen of macrophage origin. To determine whether this gene is transcribed and regulated in vascular endothelial cells, we measured HB-EGF mRNA levels in human umbilical vein endothelial cells (HUVEC) by RNA blot analysis with an HB-EGF cDNA probe. The base-line level of HB-EFG mRNA in HUVEC in culture was low. However, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta markedly increased HB-EGF mRNA levels in HUVEC by 12- and 7-fold, respectively, and induction of the gene by TNF-alpha was both dose- and time-dependent. In response to TNF-alpha, HB-EGF mRNA levels quickly increased and peaked at 1 h, indicating that HB-EGF belongs to the family of immediate early genes. In nuclear run-off experiments, TNF-alpha increased the rate of HB-EGF gene transcription by 3.2-fold. To our knowledge this is the first demonstration that the HB-EGF gene is transcribed in vascular endothelial cells. The inducible transcription of this potent SMC mitogen gene in endothelial cells suggests that HB-EGF may have an important role in the pathogenesis of atherosclerosis.

Base Sequence↗
PubMed1991

Stimulation of endothelin-1 gene expression by insulin in endothelial cells.

The present study characterized the regulation of the genetic expression of the vasoactive peptide endothelin-1 (ET-1) by insulin in bovine aortic endothelial cells. By RNA blot analysis, insulin (1.67 x 10(-8) M) increased ET-1 mRNA levels by 2.3-fold over the basal within 10 min and attained a maximum (5.3-fold increase) in 2 h. Dose-response studies showed that a maximum effect of insulin was reached at 1.67 x 10(-8) M although a significant increase can be observed at 1.66 x 10(-9) M. Radioligand receptor studies indicated that the affinity constant for insulin receptors on endothelial cells correlated closely with the dose response observed for ET-1 mRNA. The ET-1 mRNA half-life was estimated with actinomycin D studies to be 20 min in control cells and was not affected by insulin treatment. Moreover, the effects of phorbol 12-myristate 13-acetate (PMA) and insulin were additive in the induction of ET-1 gene expression. When protein kinase C in the bovine aortic endothelial cells was down-regulated by preincubation with 8 x 10(-7) M PMA for 24 or 48 h, insulin was still able to increase ET-1 mRNA levels whereas PMA was ineffective. Using a chloramphenicol acetyltransferase (CAT) fusion plasmid containing the CAT gene and the 5'-flanking region of the ET-1 gene (Lee, M. E., Bloch, K. D., Clifford, J. A., and Quertermous, T. (1990) J. Biol. Chem. 265, 10446-10450), we observed that 1.67 x 10(-8) M insulin increased CAT enzyme activity and mRNA levels. The insulin dose-response curve observed for CAT activity correlated with that observed for ET-1 mRNA levels. These results suggest that insulin stimulates expression of the ET-1 gene at the transcriptional level via its own receptors. This effect is mediated mostly through a protein kinase C-independent pathway, suggesting the existence of an insulin-responsive element in the ET-1 gene 5'-flanking sequence.

Amino Acid Sequence↗
PubMed1991

A recombinant chimeric plasminogen activator with high affinity for fibrin has increased thrombolytic potency in vitro and in vivo.

A recombinant plasminogen activator with high fibrin affinity and specificity was expressed by transfecting hybridoma cells with a plasmid that combines sequence coding for low molecular mass (32 kDa) single-chain urokinase-type plasminogen activator [scuPA(32kDa)] and anti-fibrin monoclonal antibody 59D8. The expression of the recombinant molecule [r-scuPA(32kDa)-59D8] was optimized by replacing the 3' untranslated region (initially that of high molecular mass scuPA) in the plasmid with the 3' untranslated region of either beta-globin or mouse immunoglobulin. This modification resulted in a greater than 100-fold improvement in the level of protein expression. The 103-kDa r-scuPA(32kDa)-59D8 protein displayed catalytic activity indistinguishable from that of high molecular mass scuPA and fibrin binding comparable to that of native antibody 59D8. r-scuPA(32kDa)-59D8 was 6 times more potent than high molecular mass scuPA in lysing a human plasma clot in vitro and was 20 times more potent than high molecular mass scuPA in the rabbit jugular vein model of thrombolysis. Molecules of this type may serve as prototypes for highly specific, antibody-targeted enzymes suitable for human use.

Animals↗
PubMed1991

Regulation of endothelin-1 gene expression by Fos and Jun.

The endothelin peptides constitute a family of potent vasoconstrictor molecules. Endothelin-1 (ET1) is secreted by vascular endothelial cells and may have a role in the regulation of vascular tone. To better understand the function of ET1, we have investigated the transcriptional regulation of the ET1 gene. Utilizing reporter gene transfection experiments, we have previously identified two promoter regions, located at base pairs -148 to -117 (Region A) and -117 to -98 (Region B) of the ET1 gene. Both regions are necessary for high level ET1 transcription in endothelial cells. A nuclear protein binding to the GATA motif in Region A has been identified and proven to be necessary for expression of the ET1 gene. However, the cis-acting sequences and their cognate binding proteins for Region B have not been investigated. To identify protein binding motifs in Region B we performed DNase I footprinting and gel mobility shift assays using a DNA fragment encoding base pairs -204 to -94 of the ET1 gene. Results from these studies indicated that the AP1 consensus sequence (GTGACTAA) in Region B as the only protein-binding motif. Site-directed mutagenesis of the ET1 AP1 site resulted in a 30-fold reduction in promoter activity, establishing the functional significance of this sequence. Additional experiments investigated the role of Jun and Fos in ET1 transcription. By employing antisera to Jun and Fos in gel mobility shift assays, both of these proteins were identified as endothelial cell nuclear proteins binding to the ET1 AP1 sequence. In trans-activation experiments, we showed that cotransfection of c-fos and c-jun expression plasmids markedly increased the transcription rate of chloramphenicol acetyltransferase reporter plasmids containing three synthetic ET1 AP1 sites. Taken together, these data indicate the importance of the AP1 recognition sequence, and the role of Fos and Jun proteins in the regulation of ET1 gene transcription.

Base Sequence↗
PubMed1991

Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells.

Previously, we have identified two regions (A and B) of the endothelin-1 promoter that are important for the expression of this gene in cultured vascular endothelial cells. The cis-acting sequence in one of these regions (Region A) includes the core binding motif GATA, raising the possibility that this region of DNA mediates binding of a member of the GATA-binding protein family. In this report, we describe the use of polymerase chain reaction in conjunction with cDNA cloning to characterize the GATA-binding protein expressed in endothelial cells. The nucleotide sequence of endothelial cell cDNA clones is highly homologous to that of the chicken GATA-2 (NF-E1b) gene, indicating that our clones encode the human GATA-2 gene transcript. By RNA blot analysis, this gene is expressed in cultured cell lines derived from a number of different tissues. Transactivation experiments utilizing human GATA-2 eukaryotic expression vectors indicate that the GATA-2 protein interacts with the endothelin-1 GATA sequence to increase transcription of reporter genes in both BAEC and HeLa cells. These data provide the first evidence for a non-erythroid target gene regulated by GATA-2 and indicate that GATA-2 may have a more broad role in transcriptional regulation than the erythroid-specific GATA-1 protein.

Amino Acid Sequence↗
PubMed1991

Effect of chemical conjugation of recombinant single-chain urokinase-type plasminogen activator with monoclonal antiplatelet antibodies on platelet aggregation and on plasma clot lysis in vitro and in vivo.

The murine monoclonal antiplatelet antibodies MA-TSPI-1 (directed against human thrombospondin) and MA-PMI-2, MA-PMI-1, and MA-LIBS-1 (directed against ligand-induced binding sites [LIBS] on human platelet glycoprotein IIb/IIIa) were conjugated with recombinant single-chain urokinase-type plasminogen activator (rscu-PA) using the cross-linking reagent N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). The conjugates (rscu-PA/MA-TSPI-1, rscu-PA/MA-PMI-2, rscu-PA/MA-PMI-1, and rscu-PA/MA-LIBS-1), purified by immunoadsorption and gel filtration, were obtained with recoveries of 34% to 45%, with an average stoichiometry of 1.6 to 1.8 IgG molecules per rscu-PA molecule, and with unaltered specific activities and affinities. Preincubation of human platelet-rich plasma with rscu-PA/MA-PMI-2, rscu-PA/MA-PMI-1, or unconjugated rscu-PA resulted in partial inhibition of ADP-induced aggregation; 25% inhibition was obtained with 63 micrograms/mL rscu-PA and with 6 micrograms u-PA/mL rscu-PA/MA-PMI-2 or 1.2 micrograms u-PA/mL rscu-PA/MA-PMI-1. In an in vitro system composed of a 125I-fibrin-labeled platelet-rich human plasma clot immersed in normal human plasma, the conjugates had threefold to greater than 15-fold less fibrinolytic potency than unconjugated rscu-PA. The thrombolytic potency of rscu-PA/MA-PMI-1 and rscu-PA/MA-LIBS-1 was compared with that of rscu-PA and that of a control conjugate rscu-PA/MA-1C8 in a pulmonary embolism model in the hamster, using clots prepared from platelet-poor or platelet-rich human plasma. Lysis was measured 30 minutes after the end of a 60-minute intravenous infusion of the thrombolytic agents. rscu-PA, rscu-PA/MA-PMI-1, rscu-PA/MA-LIBS-1, as well as rscu-PA/MA-1C8 had comparable thrombolytic potencies (percent lysis per dose administered) towards platelet-poor human plasma clots. In contrast, the thrombolytic potency of rscu-PA/MA-PMI-1 and of rscu-PA/MA-LIBS-1 towards platelet-rich clots was 2.3- to 3-fold higher than that of rscu-PA (P less than .005) and fivefold to sevenfold higher than that of the control conjugate (P less than .01).

Adenosine Diphosphate↗