Biomedical subjects
Publications and source records attributed to E R Hall.
Because rape occurs more frequently in adolescence than at any other age, the adequacy of services for adolescent victims of rape is a public health concern. This survey found that adolescents had favorable attitudes toward sexual assault treatment centers but that a center's affiliation, staff, and policies on confidentiality would influence young people's willingness to use its services.
To understand the pathophysiologic significance of abnormal serum prostacyclin (PGI2) binding activities in thrombotic thrombocytopenic purpura (TTP), we evaluated the PGI2 binding characteristics in three chronic TTP sera and 19 normal sera. PGI2 binding by serum was rapid and reversible. The binding activity in TTP sera (22.1 +/- SD, 4.4%) was significantly lower than that of normal sera (42.2 +/- 6.2%). Moreover, the antiaggregating activity and 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) content in the gel filtrates representing the binding peak was proportionally lower in a TTP serum than normal serum. Although normal and TTP sera bound [14C]arachidonate with similar activity, and neither bound [3H]6KPGF1 alpha, there was a difference in prostaglandin E1 (PGE1) binding. Binding of [3H]PGE1 was subnormal in two TTP sera (W.J. and T.G.) and normal in the third (H.S.). Normal serum corrected the binding defects of TTP serum. Interestingly, the mixture of two TTP sera (W.J. and H.S.) mutually corrected their PGI2 binding defects. In addition, although in vivo plasma transfusions improved the PGI2 binding activity of W.J. and H.S., there existed a striking difference in the nature of their response. These observations indicate that there is at least two types of PGI2 binding defects in TTP. Our data indicate that TTP is associated with diminished serum binding of PGI2. This defect may reduce the availability of PGI2 to damaged vascular sites and decrease an important modulator of platelet thrombus formation at times of severe vascular insult.
The uptake of arachidonate and stearate from serum-free media by endothelial cells was investigated over a 48 h period. Arachidonate was rapidly incorporated into both the phospholipids and triacylglycerols. Triacylglycerol incorporation reached a maximum at 2 h and then rapidly declined with a concomitant increase in phospholipid incorporation. High initial arachidonate incorporation into phosphatidylcholine was followed by a partial transfer of that arachidonate to phosphatidylethanolamine. In contrast, stearate was slowly incorporated into all of the phospholipids and was not incorporated into the triacylglycerols. Cells stimulated with A23187 for 24 h cleaved stearate from all the phospholipids equally, whereas more arachidonate was cleaved from phosphatidylethanolamine than from the other phospholipids. Released arachidonate was both metabolized and reacylated into the triacylglycerols. Our results suggest that triacylglycerols serve as a modulator of intracellular arachidonate concentrations in endothelial cells.
Nine underivatized prostaglandins were examined using direct exposure, ammonia, chemical-ionization, pulsed positive-negative ion mass spectrometry. The positive ion spectra were characterized by (M+18)+ ion adducts. The negative ion spectra were characterized by ions which depended upon the functionality present in the cyclopentane ring system (acetal for TXB2). The E and D series prostaglandins gave (M-18)- as the major negative ion, while the F series and TXB2 were characterized by negative ions corresponding to (M-1)-, and PGA2 by the parent (M)- ion. Prostaglandin 6-keto-PGF1 alpha was anomalous in this respect showing apparent dehydration, interpreted as an overall (M-18+1)+ and (M-18-1)- in the positive and negative ion spectra, respectively. All major ion types were shown to give essentially a linear response with respect to concentration in the 10-1000 ng range. Although these initial studies were conducted under ideal conditions, it would appear that direct chemical ionization techniques show promise for providing direct structural information on prostaglandins without the need for prior chemical derivatization.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effects of oral contraceptive (OC) usage on platelet responsiveness to arachidonic acid metabolites was investigated. Platelets obtained from women who had been taking oral contraceptives for at least 3 months were compared with those of age-matched controls. Both the basal and prostacyclin (PGI2)-stimulated platelet cAMP levels were significantly lower in OC users than in non-users. There was no significant difference in the PGD2-stimulated cAMP levels between the two groups. Furthermore, platelet aggregability to U46619, a TXA2 agonist, was greatly enhanced by OCs. Our data suggests that OC usage can specifically enhance platelet responsiveness to TXA2 while suppressing platelet responsiveness to PGI2. Thus their overall effect would be a disruption of normal platelet responses in favour of thrombus formation.
It has been postulated that metabolites of the arachidonic acid pathway exert an important influence on hemostasis and thrombosis. This notion is based on in vitro experiments. We have utilized two experimental models to elucidate the physiologic roles of thromboxane A2 (TxA2) and prostacyclin (PGI2) in the modulation of thrombus formation. The role of TxA2 in promoting thrombus formation was evaluated in a rabbit model where the aorta was deendothelialized by a balloon catheter technique and indium-111-labeled platelets were used as a marker for quantifying platelet deposition. Both 1-benzylimidazole, a thromboxane synthase inhibitor, and 13-azaprostanoic acid, an antagonist of thromboxane/endoperoxide receptors significantly reduced the platelet deposition onto the damaged vessel wall. The data indicate the TxA2 plays an important role in thrombosis and hemostasis. The influence of PGI2 insufficiency due to accelerated PGI2 degradation on microvascular thrombosis was evaluated in a unique clinical disease, i.e. thrombotic thrombocytopenic purpura (TTP). Accelerated PGI2 degradation was observed in several patients with chronic TTP. The degradation abnormalities were corrected by plasma infusion in vivo or serum supplement in vitro. To test the hypothesis that PGI2 must be bound to serum macromolecules to prevent rapid hydrolysis, serum binding capacity for PGI2 was measured by Sephadex G-25 gel filtration. The binding capacity was significantly reduced in the patients and was corrected by serum supplement. Abnormalities of PGI2 binding were also noted in a group of patients with ischemic stroke. Our findings suggest that there exist in the serum certain constituents which bind and stabilize PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)
The cost-effectiveness of biological processes has encouraged many researchers to consider biotreatment for the stabilization of toxic or recalcitrant wastewaters. However, to ensure adequate removal of trace contaminants and satisfactory performance with high strength inhibitory industrial wastewaters, conventional biotechnology is being re-evaluated. This review summarizes selected recent contributions to the development of appropriate biotechnology for toxic wastewater treatment. Microbiological constraints and potential solutions are examined. Assessments of conventional biological processes for contaminant control are reviewed, and several new developments in bioreactor design for inhibitory wastes are presented.
The role of thromboxane A2 (TXA2) in platelet-vessel wall interaction was investigated using 1-benzylimidazole (1-BI), a selective thromboxane synthetase inhibitor. 1-BI (0.9 mM) will reduce the aggregatory response of rabbit platelets to 0.2 mM arachidonate by 50% and their production of TXA2 by 84%. The effect of 1-BI on platelet thrombus formation was evaluated in vivo on New Zealand white male rabbits using the autologous indium-111 labeled platelet technique. After injection of autologous 111In-platelets, 10 cm of the abdominal aorta was de-endothelialized with a balloon catheter. Three hours later the animals were sacrificed and injured and uninjured segments of the aorta removed. The radioactivity and dry weight of the tissue were determined. The radioactivity/gm of tissue was greater for the injured tissue than for the uninjured tissue. 1-BI at 10 mg/kg reduced the specific platelet accumulation at the injured site (n = 5; 4.8 +/- 0.3 X 10(5) cpm/gm) compared to the controls (n = 10; 11.7 +/- 2.1 X 10(5) cpm/gm). Platelet accumulation on the injured tissue was further reduced by increasing the dosage to 30 mg/kg. Thirty minutes after 1-BI administration (30 mg/kg), platelets were less sensitive to arachidonate-induced aggregation (a 67% decrease) and TXA2 production was decreased 82%. Alterations in platelet sensitivity persisted for up to 3 hours. These findings indicate that TXA2 plays an important role in platelet-vessel wall interaction.
Explore the source record for details and available documents.
Synthesis of thromboxane B2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid by crude microsomes and by partially purified thromboxane synthetase from porcine lung has been studied. Formation of both compounds catalyzed by the purified enzyme is inhibited similarly by imidazole or increased temperature (52 degrees C). However, during the initial stages of purification only the production of thromboxane B2 was diminished by imidazole or increased temperature, indicating the presence of an additional mechanism for the formation of 12-L-hydroxy-5,8,10-heptadecatrienoic acid. This novel mechanism is attributed to the effect of nondialyzable heat-stable factor(s) present in the crude preparation which stimulates the formation of 12-L-hydroxy-5,8,10-heptadecatrienoic acid from prostaglandin H2 in a time-dependent manner.
Plasma prostacyclin (PGI2) degradation rate was measured in a 39-year-old man with chronic thrombotic thrombocytopenic purpura (TTP). His disease responded to plasma exchange, or plasma infusion alone, given at 3-4 week intervals. Plasmapheresis with albumin replacement had an adverse effect. PGI2 degradation rate was measured by incubation of exogenous PGI2 with plasma at 37 degrees C and recording of PGI2 activity after one, five, and fifteen min incubation by measurement of inhibition of platelet aggregation. The PGI2 degradation rate of the patient was significantly higher than that of normal subjects. The degradation rate improved after each plasma treatment and correlated well with clinical improvement. Moreover, the degradation rate of PGI2 could be corrected in vitro by the addition of normal plasma. When the patients plasma was incubated with aortic rings, PGI2 activity was reduced but the level of its inactive end product, 6-keto-PGF1 alpha, was normal. These findings indicate that our patient had normal PGI2 stimulating activity but had an abnormal rate of PGI2 degradation. Accelerated PGI2 degradation which leads to PGI2 deficiency may be important in the pathogenesis of microvascular thrombosis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Human erythrocyte acetylcholinesterase was incorporated into liposomes of different phospholipid composition by detergent depletion methods. Complete incorporation of activity into liposomes was achieved. Either by gel filtration or by dialysis 99.96% of the sodium deoxycholate originally present was removed. The preferred method of liposome formation involved the use of dialysis followed by gel filtration, as gel filtration alone resulted in liposomes heterogeneous in size. The liposomes had a diameter of about 30 nm (determined by electron microscopy and gel filtration). Studies involving the use of Triton X-100 and proteolytic enzymes revealed that at least 70% of the incorporated activity was located on the outer-side of the liposomes; this percentage was even higher in small liposomes.
Explore the source record for details and available documents.
Explore the source record for details and available documents.