Evaluation of low PAI-1 activity as a risk factor for hemorrhagic diathesis.

BACKGROUND: Prospective studies of the epidemiology and clinical significance of low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking. OBJECTIVE: To evaluate the prevalence of low PAI-1 activity in patients with a bleeding tendency in comparison with a normal population. METHODS: In 586 consecutive patients, referred because of bleeding symptoms, we added analyses of PAI-1 activity and tissue plasminogen activator complex with PAI-1 (t-PA-PAI-1) to the routine investigation, consisting of platelet count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, von Willebrand factor activity, and antigen. Controls were 100 blood donors and 100 age- and sex-matched healthy individuals. The latter were also evaluated regarding the previous bleeding episodes. The bleeding history was classified as clinically significant or not, and the criteria were fulfilled in 75% of the patients and 18% of the healthy controls. RESULTS: The routine laboratory investigation of the patients was negative in 57%. Low PAI-1 activity, defined as <1.0 U mL(-1), was found in 23% of the patients and in 13% and 10% of the blood donors and healthy controls, respectively (odds ratio and 95% CI, 2.04; 1.11-3.77 and 2.75; 1.39-5.42, respectively). The difference remained statistically significant after the adjustment for body mass index, use of estrogens, sex and age (odds ratio for patients vs. healthy controls 3.23; 95% CI, 1.22-8.56, P = 0.019). The distribution of the 4G/5G genotypes in the patients was not different from that of two control populations. No specific symptom predicted for low PAI-1, which did not aggravate the clinical picture in association with the other hemostatic defects. Low tPA-PAI-1 was not associated with the increased bleeding tendency. CONCLUSION: Low PAI-1 activity is common in patients with a bleeding diathesis, but it is a risk factor of minor clinical importance and not associated with specific bleeding manifestations.

Passive IgE-sensitization by blood transfusion.

BACKGROUND: To study the mechanisms of passive sensitization of patients receiving plasma containing IgE antibodies to a defined allergen. METHODS: When required for medical reasons, regular donor plasma with IgE antibodies to timothy grass allergen (8-205 kU(A)/l), was given. Kinetics of IgE antibodies in the recipients' serum and his/her basophil allergen threshold sensitivity, CD-sens, was monitored up to 2-3 weeks after transfusion. The IgE antibodies were quantitated by ImmunoCAP. The CD-sens in plasma recipients, determined by CD63 up-regulation, was measured by flow cytometry and compared to CD-sens of patients with allergic asthma and/or rhinitis. RESULTS: There was a significant correlation (r = 0.98; P < 0.001) between amount of IgE antibody given and recipient serum peak concentration. The T(1/2) for IgE antibody in circulation was 1.13 days (95% confidence limit 0.35-1.91 days). The recipients became CD-sens positive already 3 h after transfusion. The CD-sens peak was observed after 3.4 days and the value were correlated (r = 0.68; P < 0.02) to the amount of IgE antibody transfused and were of the same magnitude as found in allergic patients. The T(1/2) of CD-sens indicated two populations of basophils; one with a CD-sens decrease T(1/2) of 4 days and one of 10 days. CONCLUSION: Transfused IgE antibodies will sensitize mast cells and basophils to CD-sens levels similar to those of allergic patients. The recipients expressed 'slow' or 'rapid' CD-sens decline, indicating two different basophil populations. After transfusion of plasma with >10 kU(A)/l IgE antibody the recipient could have allergen reactive basophils for up to 7 weeks.

Cavitation fatigue. Embolism and refilling cycles can weaken the cavitation resistance of xylem.

Although cavitation and refilling cycles could be common in plants, it is unknown whether these cycles weaken the cavitation resistance of xylem. Stem or petiole segments were tested for cavitation resistance before and after a controlled cavitation-refilling cycle. Cavitation was induced by centrifugation, air drying of shoots, or soil drought. Except for droughted plants, material was not significantly water stressed prior to collection. Cavitation resistance was determined from "vulnerability curves" showing the percentage loss of conductivity versus xylem pressure. Two responses were observed. "Resilient" xylem (Acer negundo and Alnus incana stems) showed no change in cavitation resistance after a cavitation-refilling cycle. In contrast, "weakened" xylem (Populus angustifolia, P. tremuloides, Helianthus annuus stems, and Aesculus hippocastanum petioles) showed considerable reduction in cavitation resistance. Weakening was observed whether cavitation was induced by centrifugation, air dehydration, or soil drought. Observations from H. annuus showed that weakening was proportional to the embolism induced by stress. Air injection experiments indicated that the weakened response was a result of an increase in the leakiness of the vascular system to air seeding. The increased air permeability in weakened xylem could result from rupture or loosening of the cellulosic mesh of interconduit pit membranes during the water stress and cavitation treatment.

Canny's compensating pressure theory fails a test.

Canny's compensating pressure theory for water transport (American Journal of Botany 85: 897-909) has evolved from the premise that cavitation pressures are only a few tenths of a megapascal negative (approximately -0.3 MPa). In contradiction, "vulnerability curves" indicate that xylem pressures can drop below -3 MPa in some species without causing a loss of hydraulic conductivity. Canny claims these curves do not measure the limits to negative pressure by cavitation, but rather the limits to the compensating tissue pressure that otherwise quickly refills cavitated conduits. Compensating pressure is derived from the turgor pressure of the living cells in the tissue. To test this claim, we compared vulnerability curves of Betula nigra stems given three treatments: (1) living control, (2) killed in a microwave oven, and (3) perfused with a -1.5 MPa (10% w/w) mannitol solution. According to Canny's theory, the microwaved and mannitol curves should show cavitation and loss of conductance beginning at approximately -0.3 MPa because in both cases, the turgor pressure would be eliminated or substantially reduced compared to controls. We also tested the refilling capability of nonstressed stems where compensating pressure would be in full operation and compared this with dead stems with no compensating pressure. According to Canny's interpretation of vulnerability curves, the living stems should refill within 5 min. Results failed to support the compensating tissue theory because (a) all vulnerability curves were identical, reaching a -1.5 MPa threshold before substantial loss of conductance occurred, and (b) killed or living stems had equally slow refilling rates showing no significant increase in conductivity after 30 min. In consequence, the cohesion theory remains the most parsimonious explanation of xylem sap ascent in plants.