Biomedical subjects
Publications and source records attributed to F Dunn.
The effects of 25 kHz ultrasound on murine testes was studied, as mimicking possible World WAR II SONAR exposure to swimming maintenance personnel. Very few specimens were found to exhibit morphological tissue alterations, depending upon length of exposure time and proximity of the source to the tissue. Thermal processes seem to be eliminated, but microstreaming may be implicated, as the physical mechanism(s) of interaction.
Light and electron microscopy were employed to examine ultrasonically irradiated murine neonate spinal cords. Spinal cord damage was always associated with functional changes, i.e. hind limb paralysis, and was never apparent in initially paralyzed specimens which had recovered function. Damage occurred preferentially at the periphery of the spinal cord and on the ventral side, though the ultrasound was incident on the dorsal side. The distribution of the damage suggests spinal column involvement and nonthermal effects that are enhanced by temperature elevation.
The dependence of the speed of sound and the attenuation coefficient upon exposure frequency, in the range of 1-5 MHz, and upon level of inflation, in the range of mass density 0.35-0.7 g/cm3, are reported. The speed of sound decreases linearly and the attenuation coefficient increases exponentially, for all levels of inflation studied.
A new role for platelets in fibrinolysis is proposed. Platelets (euglobulin from platelet rich plasma and from human platelet extract) may potentiate plasminogen activation by tissue plasminogen activator (tPA). The potentiating activity was detected by both chromogenic substrate and fibrin plate analysis. The fibrinolysis-potentiating substance in the platelets required the presence of both tPA and plasminogen, suggesting that it potentiates the activation of plasminogen by tPA. This substance was not related to fibrinogen degradation products because it was also present in platelets from two afibrinogenemic patients and did not lose its activity when separated from fibrinogen-related antigen by Sepharose 2B gel filtration. Since platelets contain both activator(s) and inhibitor(s) of plasminogen activation by tPA, a balance between activator(s) and inhibitor(s) in platelets may also be required for control of the fibrinolytic pathway.
Inactivation of Chinese hamster V79 cells in vitro by a temperature elevation to 43 degrees C and with Couette shear flow was investigated. The shear stresses were chosen to mimic those produced by ultrasound of approximately 3 MHz and 3 W/cm2 within the chambers employed by earlier investigators studying ultrasonic inactivation of cellular processes. The combined shear and thermal stresses produced survival curves exhibiting a summating effect among these two stresses and remarkably similar to the ultrasound/thermal survival curves.
The specific ultrasonic absorption coefficient per wavelength as a function of temperature in the vicinity of the phase transition of liposomes, composed of a 4:1 mixture of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG), of different sizes was determined using an acoustic interferometer. Small unilamellar vesicles (SUV) and multilamellar vesicles (MLV) yielded results similar to those in the literature, viz., an absorption maximum at the transition temperature. Seven intermediate sizes including several size distributions of large unilamellar vesicles (LUV) were studied, yielding information on size dependencies of the temperatures at which the peaks occur, the widths at half peak amplitude, and the peak amplitudes. All liposome sizes except the SUV exhibited approximately the same transition temperature as did the largest MLV. The widths of the peaks were inversely related to liposome size, with a strong dependence for the smallest vesicles and an approach to independence for the largest vesicles. The amplitudes of the peaks exhibited a general increase with size with two exceptions, viz., the SUV and the vesicles with average diameters of 90-100 nm. It was also found that the membrane permeability increased near the transition temperature. The temperature dependencies of ultrasonic absorption and membrane permeability are compared.
Previous experiments demonstrated that chymotrypsin, but not adenosine diphosphate (ADP), exposed fibrinogen binding sites on platelets from patients with Glanzmann's thrombasthenia. Three of these patients have been reexamined, and previous observations were confirmed. The quantity of iodine 125-labeled glycoprotein IIb (GPIIb) and glycoprotein IIIa (GPIIIa) on the platelets of these patients was considerably less than normal but was detectable by immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and autoradiography. The amount of residual GPIIb and GPIIIa as measured by binding studies with radiolabeled monoclonal antibodies was between 3% and 12% of the normal value. Platelet suspensions from these patients did not aggregate with fibrinogen and did not bind 125I-fibrinogen on stimulation with ADP. However, incubation of these platelets with chymotrypsin or pronase resulted in fibrinogen binding and platelet aggregation. Monoclonal antibodies specific for the GPIIb-GPIIIa complex blocked both the fibrinogen binding and the aggregation of enzyme-treated platelets. The treatment of washed platelets of a fourth thrombasthenic patient with ADP or with chymotrypsin failed to result in fibrinogen binding and aggregation. However, the level of GPIIb and GPIIIa on these platelets as measured by a Western blot technique and by monoclonal antibody binding amounted to less than 0.35% to 0.5% of normal values. In conclusion, fibrinogen binding sites exposed on thrombasthenic platelets by chymotrypsin are derived from GPIIb-GPIIIa molecules. Aggregation of chymotrypsin-treated thrombasthenic platelets by fibrinogen appears to represent a sensitive test for detection of functionally active GPIIb-GPIIIa complex on the platelet surface.
The ultrasonic absorption of large unilamellar vesicles (average diameter 0.2 micron) was determined in the frequency range 0.5-5 MHz. The liposomes were composed of a 4:1 mixture by weight of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidylglycerol. They were studied with and without cholesterol or gramicidin incorporated into the bilayer. A large increase in absorption occurs at the solid to liquid-crystalline phase transition temperature (42 degrees C) of the pure lipid vesicles. This increase in absorption is interpreted as a structural relaxation of the 'melting' fatty acid chains occurring with an average relaxation time of 76 ns. The liposomes were also found to be extremely permeable near the transition temperature. Essentially complete release of cytosine arabinoside, a small water-soluble molecule, occurred at 42 degrees C. Addition of cholesterol or gramicidin to the bilayer of the liposomes broadened the ultrasonic absorption and reduced the efflux of cytosine arabinoside at the phase transition. No increase in absorption was observed at the transition temperature in the presence of 50 mol% of cholesterol. Gramicidin, in addition to broadening the transition, slows the isomerization of bonds in the hydrocarbon chains of the lipids. A concentration of 5 mol% gramicidin increased the average relaxation time to 211 ns.
Explore the source record for details and available documents.
An abnormal plasminogen was discovered because of a decreased level of plasminogen activity in plasma contrasting with a normal level of plasminogen antigen concentration. The same discrepancy was found in the purified plasminogen. The molecular abnormality seems to be inherited. The patient is a heterozygote. The experimental findings can be explained by assuming that half of the plasminogen is normal, while the other half is an inactive mutant protein, without catalytic activity after SK or UK addition. There was no binding of labeled DFP and a decreased binding of TLCK to the abnormal plasminogen. The role of the abnormal plasminogen in thrombotic tendency is uncertain since the patient is the only one who has suffered a thrombotic accident, while her relatives who present the same defective plasminogen have not had thrombotic problems.
Unfractionated heparin increased the binding of fibrinogen on ADP-treated platelets. The results varied according to both, the platelets of the donor and the kind of heparin preparation used. Beef lung heparin was more active than porcine intestinal mucosa heparin (p less than 0.02). A fraction of low molecular weight low sulfated heparin, did not significantly increase the binding of fibrinogen, except in one case for which the binding of fibrinogen to platelets was largely increased by standard heparin. On the contrary, pentosane polysulfate, a sulfated polysaccharide (of low molecular weight) significantly increased the binding of fibrinogen (p less than 0.01).
Explore the source record for details and available documents.
In the presence of an excess of streptokinase (SK) the amidolytic activity of the plasminogen-SK complex on chromogenic substrates is 12% lower in serum than in the corresponding plasma. However, in subjects in whom venous stasis lead to a shortening of the euglobulin lysis time to less than 60 min (high responders), the amidolytic activity of the plasminogen-SK complex in serum was 60% higher than in the corresponding plasma. Attempts to find alterations of the plasminogen molecule itself which would account for the enhanced activity in high responder serum were negative. No free plasmin was present and the plasminogens isolated from plasma and serum before and after venous stasis had the same amidolytic activity as gluplasminogen in the presence of an excess of SK. N-terminal analysis of these four plasminogens revealed in each instance glutamic acid. The enhancement of the amidolytic activity of the SK-plasminogen complex in serum of high responders (potentiator activity) could be reproduced by adding purified tissue plasminogen activator (TA) to native blood before clotting, but not if TA was added to plasma or to prestasis serum. Removal of fibrin degradation products from poststasis serum resulted in the disappearance of potentiator activity. These experiments suggest that fibrin degradation products, generated during clotting in the presence of vascular or tissular plasminogen activator act as a potentiator of the amidolytic activity of the plasminogen SK-complex.
Explore the source record for details and available documents.
The nonlinearity parameter B/A for several biological materials was determined by measuring the amplitude of the second harmonic pressure as a function of distance from the source and the amplitude of the fundamental at the source. The B/A values for bovine serum albumin and haemoglobin solutions were found to increase approximately linearly with solution concentration. Blood and homogenized liver exhibit a B/A value similar to a haemoglobin solution of the same dry weight, but whole liver has a greater B/A value.
Explore the source record for details and available documents.
Non-linear mechanical response of viscoelastic strain responding media to high amplitude stress-strain is examined from a phenomenological point of view and found to lead to results compatible with empirical observations of high intensity ultrasound irradiation of brain, liver, and eye lens tissues. The proposed hysteresis model provides for most of the observed dependencies such as an intensity dependent absorption coefficient, an absorption coefficient increasing linearly with frequency, and a dispersionless velocity of ultrasound in soft tissues (excluding lung). The non-linear compliance of tissues further predicts production of half-harmonic signals even in the absence of cavitation.
Explore the source record for details and available documents.