Search PubMed⌕ Search

Biomedical subjects

H C Kwaan

Publications and source records attributed to H C Kwaan.

At least 19 recordsLinked to original sources
PubMed1992

Phosphorylation of a surface receptor bound urokinase-type plasminogen activator in a human metastatic carcinomatous cell line.

The 32P-labeled urokinase (uPA) bound to surface receptors of Detroit 562 cells was immunoprecipitated by anti-uPA antibody. Amino acid analysis showed that tyrosines and serines were the acceptors. Inhibition of protein kinases greatly reduced the 32P incorporation, suggesting that the respective cellular src gene product and protein kinase C were involved in the phosphorylations. Proteins purified on chromatographic columns contained two forms of uPA, a high (HMW) and a low (LMW) molecular weight. Tyrosine-phosphorylation occurs in the HMW and A-chain. Such modifications might modulate the extracellular activities of uPA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Enzymatic properties of the phosphorylated urokinase-type plasminogen activator isolated from a human carcinomatous cell line.

Enzymatic properties of phosphorylated urokinase plasminogen activator (P-uPA) (1) extracted from human carcinomatous cell line Detroit 562 cells were compared with those of non-phosphorylated uPA of urinary origin (nP-uPA). Using plasminogen as a substrate, the Km and Kcat of P-uPA were higher than that of nP-uPA while the Kcat/Km was lower. By zymography, a greater degree of plasminogen activation was observed. Concanavalin A reacted to both the enzymes. P-uPA had a low affinity for the inhibitors of plasminogen activator PAI-1 and PAI-2, and was inhibited only by the excess amounts of inhibitors. For PAI-1, and the KIs of P-uPA was greater and for PAI-2, KI was higher for P-uPA. These alterations by phosphorylation enable uPA to be more efficient in a focal proteolysis through plasminogen activation.

Amino Acid Sequence↗
PubMed1992

The plasminogen-plasmin system in malignancy.

The study of the plasminogen-plasmin system has, in the past, contributed much to the understanding of fibrinolysis and thrombolysis. Attention is now focused on the role of the components of this system in many biologic functions. Findings of uPA, its receptor and its inhibitor in many tumor tissues and tumor cell lines, strongly implicate their involvement in tumor invasion, tumor cell proliferation and metastasis. The characteristics of the plasminogen activators, the uPA receptor and the plasminogen activator inhibitors as well as their expression and regulation in tumors and tumor cell lines are reviewed.

Amino Acid Sequence↗
PubMed1992

Changes in blood coagulation, platelet function, and plasminogen-plasmin system in diabetes.

The increased risk of thromboembolism in people with diabetes mellitus is in part due to changes in the hemostatic mechanism including abnormal platelet function leading to platelet activation, increase in several coagulation factors, decrease in natural anticoagulants, and impaired fibrinolytic activity. Both microangiopathy and atherosclerosis in people with diabetes will enhance the thrombotic potential of these abnormal hemostatic changes. The recent recognition of a role of the components of the plasminogen-plasmin system in many biologic functions at the cellular level has led to studies showing that the angiopathic complications of diabetes may also be caused by impaired plasminogen activator function.

Blood Coagulation↗
PubMed1992

Comparison of dosage schedules of rt-PA in the treatment of proximal deep vein thrombosis.

This study assessed the efficacy and safety of increasing durations of constant-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) in the treatment of deep vein thrombosis. Patients with venogram-documented proximal lower limb (popliteal, iliofemoral) or upper limb (axillary, subclavian) thrombi were given an initial 2-hour rt-PA infusion at 4 micrograms/kg/min, followed by a maintenance infusion of 1 microgram/kg/min for an additional 4, 22, or 33 hours (mean total rt-PA dosages of 54, 127, and 185 mg). A new quantitative venogram scoring system was applied to the study, based on measurements of thrombus volume before and after completion of treatment. Whereas none of the seven patients given treatment for 6 hours and only one of four given treatment for 24 hours showed significant lysis, four of seven who received a prolonged infusion for 35 hours showed lysis of more than 40% of the original thrombus. Overall, the prolonged 35-hour infusion induced 51% lysis of original thrombus, representing a thrombus volume of 16.7 ml dissolved. Hemorrhagic complications were common in all three groups, with four of 18 patients having significant bleeding, including one massive gastrointestinal hemorrhage, two patients with a decrease in hematocrit of more than 10%, and one patient with an intracranial hemorrhage who recovered completely. Pharmacokinetics of the rt-PA showed a steady state antigen concentration of 240 ng/ml and activity of 200 IU/ml during the initial 2-hour infusion and a postinfusion half-life of 5 minutes. Plasma fibrinogen concentrations decreased to approximately 40% to 50% of initial values with all three treatment regimens, but the nadir fibrinogen concentrations did not correlate with either therapeutic efficacy or bleeding complications. One patient with systemic lupus erythematosus had an unusual allergic reaction that manifested primarily as angioedema. This study suggests that rt-PA infusion of 35 hours induces greater thrombolysis of deep vein thrombosis than does a shorter course of 6 or 24 hours, without an increase in hemorrhagic complications.

Adult↗
PubMed1991

Heterogeneity in plasminogen activator (PA) levels in human prostate cancer cell lines: increased PA activity correlates with biologically aggressive behavior.

Plasminogen activators (PA), particularly the lower Mr urokinase (u-PA) type, have been associated with tumor cell invasion and metastasis. We have examined the expression of PA by two human prostate cancer cell lines (PC-3 and DU-145) using functional and immunologic techniques. The culture media and cell extracts of the more aggressive PC-3 cell line contained more than two-fold greater PA activity than the relatively indolent DU-145 cell line. Zymographic studies identified the PA expressed as u-PA. PC-3 cells expressed an additional lower molecular weight form of u-PA not noted in DU-145 cells. Heterogeneity in u-PA expression was shown by the fibrin lysis assay, immunohistochemistry, and dual parameter flow cytometry indicating the presence of phenotypically divergent cell populations. Increased u-PA expression may identify those tumor cells that possess aggressive biological potential.

Flow Cytometry↗
PubMed1990

Neurovascular fibrinolytic activity in normal Lewis rats and rats with cell-transferred experimental allergic encephalomyelitis.

Fibrinolytic activity in the form of plasminogen activator (PA) was assessed using a histochemical fibrin slide technique in spinal cords of normal Lewis rats and rats with the cell-transferred form of experimental allergic encephalomyelitis (EAE). PA was localized exclusively to blood vessels. Vessels in the leptomeninges had maximum activity. A precipitous decrease in PA activity occurred in recipient rats which coincided with onset of clinical neurologic signs. A subsequent return in activity occurred in association with clinical remission of disease but remained well below the activity level of normal rats for as long as the recipient animals were followed. Vessels containing perivascular cellular infiltrates of EAE had little or no detectable PA activity. Furthermore, PA could not be demonstrated to be associated with infiltrating inflammatory cells, including macrophages. These findings provide further support for involvement of the coagulation and fibrinolytic systems in the early clinical manifestations of EAE in Lewis rats.

Animals↗
PubMed1990

Quantitation of venous clot lysis with the D-dimer immunoassay during fibrinolytic therapy requires correction for soluble fibrin degradation.

Plasma cross-linked fibrin-degradation products were analyzed using a D-dimer (DD) immunoassay in patients with deep vein thrombosis (DVT) or acute myocardial infarction (MI) treated with fibrinolytic therapy, and the results were correlated with clot lysis documented angiographically. In 13 patients with DVT, the mean DD concentration increased 10-fold (1,074 +/- 252 to 10,333 +/- 1,004 ng/ml) during therapy, but neither the peak level nor the DD concentration integrated over the course of therapy correlated with clot lysis. Since plasma DD can derive from degradation of soluble plasma fibrin as well as from thrombi, the contribution of the former was estimated by in vitro incubation of the pretreatment plasma with plasminogen activator. Subtraction of this value from the measured posttreatment DD concentration provided a "corrected" level that represented DD originating from lysis of thrombi. This modification resulted in improved correlation of DD levels with clot lysis. The mean corrected peak DD was higher in patients with successful thrombolysis (8,780 +/- 1,352 ng/ml) compared with patients without lysis (3,075 +/- 589 ng/ml, p less than 0.001). There was a moderate correlation between the volume of clot lysed and the corrected peak DD (r = 0.62) and a higher correlation with the corrected DD integrated over the course of treatment (r = 0.97). By contrast, the corrected DD concentrations were near zero in patients treated for MI with or without thrombolytic reperfusion, suggesting that fibrin in small coronary thrombi did not contribute significantly to total plasma DD during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Plasminogen activators in human prostate cancer cell lines and tumors: correlation with the aggressive phenotype.

The levels of several tumor associated proteases, including plasminogen activators (PA), are elevated in many malignant tumors compared to their benign tumor counterparts. Extracellular matrix degradation mediated by PA may facilitate tumor cell invasion and metastasis. To assess whether PA content correlates with the aggressive phenotype in prostate cancer, we studied these activators in the PC-3 human prostate cell line and PC-3CALN, an aggressive in vivo derived variant cell line. Enzymatic assays using H-D-val-leu-lys-pNA (S-2251) as substrate and peroxidase-anti-peroxidase immunohistochemical techniques were used. In an in vitro chemoinvasion assay, the PC-3CALN variant cell line demonstrated significantly greater invasive behavior than the unselected, parental PC-3 line. The activity of PA secreted by PC-3CALN cells was 3.5 times greater than that of PC-3 cells (p less than 0.01). PC-3 metastases obtained following intrasplenic injection of PC-3 cells had greater PA activities than the corresponding primary tumors. Immunohistochemical studies of PC-3 tumors demonstrated preferential localization of urokinase-type PA to areas of apparent tumor cell invasion. These data suggest a correlation between PA and the aggressive phenotype in this model of human prostate cancer. PA, in particular u-PA, may play a role in the migration and invasion of prostate cancer cells and provide a marker of the aggressive phenotype.

Animals↗
PubMed1989

Fatal thrombotic thrombocytopenic purpura despite plasmapheresis. A case report of autopsy findings.

Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and renal dysfunction. Prior to modern therapy, fewer than 3% of patients survived. However, with plasmapheresis, up to 82% of patients survive. We report a case of recurrent TTP which proved fatal despite plasmapheresis. At autopsy the hyaline thrombi found were notably smaller and of shorter duration than those of untreated TTP. These findings suggest that therapy had brought about an abatement of the microthrombotic process in spite of the fatal outcome.

Autopsy↗
PubMed1988

Reproducibility of two in vivo tests of platelet function.

We correlated repeat determinations of platelet aggregate ratios (PAR) and plasma beta-thromboglobulin (BTG) in the right and left arms of thirty-four subjects in order to measure test reproducibility and to evaluate the effects of venipuncture. The reproducibility of PAR on the same blood samples was relatively low but similar to that obtained when the right arm and left arm values were compared, thus indicating little variation secondary to venipuncture. For BTG, the reproducibility on identical blood samples was quite high, but fell significantly when plasma samples from the two sides were correlated. This finding and increased BTG values when obvious blood collection problems occurred, indicated that plasma BTG levels are quite sensitive to venipuncture technique.

Humans↗