Biomedical subjects

H Kwaan

Publications and source records attributed to H Kwaan.

4 recordsLinked to original sources

PubMed2000

A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo.

Urokinase plasminogen activator (uPA) plays an important role in the progression of several malignancies including breast cancer. We have identified a noncompetitive antagonist of the uPA-uPAR interaction derived from a nonreceptor binding region of uPA (amino acids 136-143). This 8-mer capped peptide (A6) inhibited breast cancer cell invasion and endothelial cell migration in a dose-dependent manner in vitro without altering cell doubling time. Intraperitoneal administration of A6 resulted in a significant inhibition of tumor growth and suppressed the development of lymph node metastases in several models of breast cancer cell growth and metastasis. Large areas of tumor necrosis and extensive positive staining by TUNEL were observed on histological and immunohistochemical analysis of experimental tumor sections from A6-treated animals. A6 treatment also resulted in a decrease in factor VIII-positive tumor microvessel hot-spots. These results identify a new epitope in uPA that is involved in the uPA-uPAR interaction and indicate that an antagonist based on this epitope is able to inhibit tumor progression by modulating the tumor microenvironment in the absence of direct cytotoxic effects in vivo.

Amino Acid Sequence↗

PubMed1985

Diagnosis of septic pelvic thrombophlebitis by measurement of fibrinopeptide A.

Septic pelvic thrombophlebitis is an uncommon but potentially life-threatening complication of puerperal endometritis. The lack of specific physical findings necessitates a diagnosis based by exclusion on the patient's response to anticoagulation. Fibrinopeptide A (FPA) is the first peptide cleaved from fibrinogen during thrombin-mediated fibrin generation. Because of its short half-life, FPA accurately reflects the level of ongoing fibrin generation. In a preliminary study of 40 puerperal patients, FPA successfully differentiated puerperal fever secondary to endometritis or abscess from fever responsive to a heparin trial. The mean FPA level in patients presumed to have septic pelvic thrombophlebitis was 23.8 ng/ml as opposed to 7 ng/ml in patients with endometritis. No patient with septic pelvic thrombophlebitis as diagnosed by her response to a heparin trial had a level of FPA less than 14 ng/ml. There was no overlap of FPA levels between patients with endometritis or abscess and septic pelvic thrombophlebitis. The data suggest further prospective evaluation of FPA for the diagnosis of septic pelvic thrombophlebitis is warranted.

Anti-Bacterial Agents↗

PubMed1984

Fibrin generation during the diabetic pregnancy.

Fibrin catabolism was measured during the pregnancy of insulin-dependent diabetic women in both a longitudinal and cross sectional fashion. Samples of maternal peripheral venous blood were obtained in 20 pregnant diabetic women between 26 and 38 weeks' gestational age. Fibrinopeptide A, the first peptide cleaved from fibrinogen during thrombin-mediated catabolism, was measured by radioimmunoassay. Intra-assay and interassay variation for fibrinopeptide A in this laboratory were 2% and 4% respectively. Antithrombin III activity was determined by the method of Odegaard. The patients ranged from 23 to 36 years. Overall blood glucose control was good as reflected in near-normal HbA1 fasting plasma glucose values. The mean HbA1 +/- 1 standard deviation was 7.1% +/- 1.2%. The mean fasting plasma glucose concentration was 101.9 mg% +/- 21.5 mg%. Mean FPA for the diabetic women exceeded control values at each gestational period. Significant differences were found in four of the seven intervals. While the highest FPA was noted in a patient with advanced diabetic vasculopathy, exclusion of this patient did not alter the overall findings. The findings were striking and suggest the need for a prospective study designed to account for White's classification of diabetes and the degree of glucose control. Because complications of the diabetic pregnancy include an increased risk of hypertension in the mother and sudden, unexplained fetal loss, two complications associated with abnormal clotting, the increase in fibrin catabolism in patients in tight metabolic control would suggest that events other than glucose regulation impact upon fibrin catabolism and possibly pregnancy outcome in the diabetic mother.

Adult↗

PubMed1984

Fibrin generation in normal pregnancy.

Both clinical and laboratory findings suggest that pregnancy constitutes a hypercoagulable condition; yet none of the observed laboratory changes are specific for thrombosis. An essential step involves thrombin-mediated fibrin generation. In the process, fibrinopeptide A (FPA) is cleaved from fibrinogen. Using a radioimmune assay, FPA was determined prospectively in a longitudinal and cross-sectional fashion. Fibrinopeptide A increased significantly over control by the end of the first trimester, from 1.3 ng/ml to 2.8 ng/ml. It continued to increase until 30 to 32 weeks' gestation and then plateaued at 4.3 to 4.7 ng/ml. In the immediate postpartum period, FPA remains elevated. In conclusion, thrombin generation as reflected in FPA production is increased throughout pregnancy, thus confirming a hypercoagulable milieu.

Female↗