Intimal disruption and coronary thrombosis: its role in the pathogenesis of human coronary disease.
Explore the source record for details and available documents.
Coronary Disease↗
Biomedical subjects
J Forrester
Publications and source records attributed to J Forrester.
Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B.
Streptococcal exotoxins have been implicated in the pathogenesis of a toxic shock-like syndrome and scarlet fever. Previous studies have demonstrated that these toxins are potent stimulators of human T cells and have structural homology to staphylococcal enterotoxins. In the current study, we investigated the mechanism by which streptococcal erythrogenic toxins type A (SPEA) and B (SPEB) activate T cells and compared it with anti-CD3 and the known "superantigen" staphylococcal enterotoxin B. SPEA was found to selectively activate T cells bearing V beta 8, V beta 12, and V beta 14, whereas SPEB selectively activated T cells bearing V beta 2 and V beta 8. Furthermore, fibroblasts transfected with MHC class II molecules were capable of presenting SPEA and SPEB to purified T cells. The T cell response to these toxins, however, was not MHC-restricted. Although the streptococcal exotoxins stimulated both CD4+ and CD8+ T cells, SPEA but not SPEB stimulated the CD4+ T cell subset proportionately more than the CD8+ T cell subset. Our results indicate that SPEA and SPEB, like the staphylococcal enterotoxins, are superantigens and suggest a mechanism by which they may mediate particular systemic syndromes associated with streptococcal infections.
Animals↗
Down-regulation of protein kinase C blocks 5-HT-induced enhancement in Hermissenda B photoreceptors.
Light paired with serotonin (5-HT) in vivo produces both short and long-term enhancement of generator potentials in identified B-photoreceptors in Hermissenda. The contribution of protein kinase C to the induction of enhancement was assessed by pretreatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which produces a depletion or down-regulation of protein kinase C. Presentation of light and 5-HT after an 8 h pretreatment with TPA blocked the induction of enhancement of light-evoked generator potentials. Typical enhancement produced by light and 5-HT was observed after pretreatment with an inactive phorbol (4 alpha-phorbol). These results indicate that activation of protein kinase C is an important step in the induction of enhancement.
Animals↗
Instrumental dilation of the uterine cervix in antiquity--a myth or not?
Explore the source record for details and available documents.
Cervix Uteri↗
Light paired with serotonin in vivo produces both short- and long-term enhancement of generator potentials of identified B-photoreceptors in Hermissenda.
An in vivo conditioning procedure consisting of light paired with the direct application of 5-HT to the exposed but otherwise intact nervous system of Hermissenda produces a long-term modification of phototactic behavior. The long-term change in phototactic behavior produced by in vivo conditioning is dependent upon pairing light with 5-HT. In this paper, we investigate neural correlates of in vivo conditioning detected in 2 different identified photoreceptors. We found that in vivo conditioning produces a short-term and long-term enhancement of light-evoked generator potentials recorded from medial and lateral B-photoreceptors. We show that short-term enhancement is not dependent upon pairing light with 5-HT, is observed in both lateral and medial B-photoreceptors, and is expressed by a larger peak and plateau phase of light-evoked generator potentials. In contrast to short-term enhancement, we found that long-term enhancement is dependent upon pairing light with 5-HT, is detected in only lateral B-photoreceptors, and is expressed by a larger steady-state plateau phase of light-evoked generator potentials. We also present evidence that the direct action of 5-HT interacting with light- and/or voltage-dependent processes is sufficient to mimic the effects of in vivo conditioning on long-term enhancement. These results suggest that long-term enhancement may contribute to modified phototactic behavior in Hermissenda produced by 1-trial in vivo conditioning.
Animals↗
Inhibition of protein synthesis blocks long-term enhancement of generator potentials produced by one-trial in vivo conditioning in Hermissenda.
A one-trial in vivo conditioning procedure produces short- and long-term cellular changes that can be detected in identified sensory neurons of the pathway mediating the conditioned stimulus. The memory of the associative experience in the conditioned stimulus pathway is expressed by short- and long-term enhancement of light-evoked generator potentials recorded from identified lateral and medial type B photoreceptors within the eyes of Hermissenda. To identify mechanisms of the induction and expression of short- and long-term enhancement in identified photoreceptors, we have investigated the effects of inhibiting protein synthesis during the application of the one-trial in vivo conditioning procedure. Anisomycin (1 microM) present during and after the conditioning trial blocked long-term enhancement without affecting the induction or expression of short-term enhancement. Application of a control compound, deacetylanisomycin (1 microM), or delaying the application of anisomycin until 1 hr after the conditioning trial did not block either long- or short-term enhancement. These results indicate that synthesis of proteins during or shortly after training may be a critical step in the formation of long-term memory of the associative experience.
Animals↗
Inhibition of microvascular endothelial cell proliferation by vitreous following retinal scatter photocoagulation.
Laser photocoagulation of pig retina induced breakdown of the blood-retinal barrier, with the appearance of serum proteins in the vitreous as determined by sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting techniques. Vitreous from lasered eyes inhibited the proliferation of cultured retinal microvascular endothelial cells in comparison with vitreous from non-lasered control eyes, and the inhibitory effect in the lasered eyes persisted for at least seven days. Inhibition was specific for endothelial cells, since no effect was observed when retinal pericytes or Tenon's fibroblasts were the target cells. These results suggest that indirect scatter photocoagulation may induce regression of neovascularisation by causing breakdown of the blood-retinal barrier and thus releasing into the vitreous serum components which result in inhibition of retinal microvascular endothelial cell growth.
Animals↗
The Scottish Hospital Endowments Research Trust.
Explore the source record for details and available documents.
Financial Management↗
NIH3T3 transforming gene not a general feature of atherosclerotic plaque DNA (atherosclerosis/oncogene/NIH3T3 transfection assay).
A recent study indicated that the DNA isolated from human coronary atherosclerotic lesions is capable of transforming NIH3T3 cells in culture. Using DNA isolated from rabbit aortic and human carotid atherosclerotic lesions, we failed to observe such transforming activity. Thus, NIH3T3 transforming activity does not appear to be a general feature of atherosclerotic lesions.
Animals↗
Percutaneous excimer laser coronary angioplasty.
Explore the source record for details and available documents.
Aged↗
Thermal coronary angiography: a method for assessing graft patency and coronary anatomy in coronary bypass surgery.
Thermal coronary angiography was evaluated in 50 patients undergoing 137 saphenous vein and 48 internal mammary artery bypass grafts. A total of 177 thermal coronary angiograms were performed after completion of the distal anastomoses by injection of cold cardioplegia into the vein or by reperfusion with warmer blood in the internal mammary artery grafts. These angiograms provided details of graft and anastomosis patency, flow directions, and presence of native coronary stenoses. Temperature differences between the injectant and the epimyocardium of greater than 4 degrees C resulted in high-contrast images. Thermal coronary angiograms were obtained in 173 of the 177 studied bypass grafts; 172 grafts were patent, and 1 internal mammary artery graft was occluded. Unsuspected stenoses were detected at the site of four distal anastomoses. Subsequently, two anastomoses were successfully revised and three additional grafts performed. Ninety-six native coronary stenoses were located in the recipient coronary arteries. In ten instances, the thermal coronary angiograms were obscured by excess fat or myocardium, thereby impeding correct image analysis. We conclude that thermal coronary angiography can be clinically relevant and helps improve decision making during coronary artery bypass operations.
Adult↗
[Digital thermo-coronary angiography--development and validation of the method in comparison with conventional cine-coronary angiography].
We describe the technique-thermal coronary angiography (TCA)-for real-time assessment of coronary anatomy and flow. The goal of this study was to compare thermal coronary angiography to cine coronary angiography and to validate its value for detecting stenoses. We studied the exposed LAD both in beating and arrested hearts in 11 open-chest pigs by TCA and cine angiography. We used an AGA 782 Thermovision system combined with a TIC 8000 digital image processor providing coronary images with 0.1-0.2 mm spatial and 0.1 degrees C thermal resolution, and a CFR x-ray system. The coronary arteries were catheterized via the right carotid artery, using standard 5F catheters. The thermal camera was focused at a 1m-distance to the heart surface and the x-ray was angled to LAO position. We performed simultaneous thermal and cine angiography using Angiovist 370 at different temperatures (10-40 degrees C) and injection rates (1-2.5 ml/s). Different grades of stenoses were created by snares. Thermistor probe readings of the epimyocardium and the left atrial blood were performed to reference the thermal camera measurements. We obtained high resolution TCA images of both the coronaries and of the myocardial perfusion beds whenever there was greater than 4 degrees C difference between injectate and epicardial temperature. The TCA detection of stenoses as compared to cine angiography was 29/30 (96.6%) in arrested and 36/42 (85.7%) in beating hearts. Coronary occlusion produced immediate and dramatic perfusion defects as detected by TCA. TCAs were highly reproducible. Injection rate of 2 ml/s provided optimal thermal coronary images. Thermal angiograms of the LAD were sometimes affected by large crossing coronary veins, myocardial bridges, and excess of fat pretending nonexistent coronary stenosis. TCA is a highly sensitive and reproducible method as compared to standard coronary angiography and allows for detection of coronary stenoses. The image quality was best in arrested hearts.
Animals↗
Ultrasonic plaque ablation. A new method for recanalization of partially or totally occluded arteries.
The potential application of ultrasonic energy for ablation of atherosclerotic plaques was studied in human atherosclerotic arteries with continuous and pulsed delivery of energy. With a prototype ultrasonic wire probe (n = 79 segments), there was gross reduction in vascular lesions as well as microscopic disruption of fibrous and calcified plaques. Normal portions of vessels appeared unaffected by the application of ultrasound. The prototype ultrasonic wire catheter ablated calcific deposits in less than 10 seconds. With this probe, all 26 complete atherosclerotic occlusions 0.5-5 cm in length were recanalized irrespective of the presence of calcium. Twenty-four of the segments were reopened in less than 20 seconds. By light microscopy, the site of plaque ablation was smooth, concave, and conformed to the shape of the probe tip. In 17 samples, there was evidence of thermal injury, and in six of the 79 samples studied with the prototype probe, there was vascular perforation. No vascular perforation occurred without thermal damage, when pulsed (rather than continuous) ultrasonic energy was used (n = 40) or when the duration of application was less than 30 seconds, with power output less than 25 W and with the probe oriented parallel to the wall (n = 26). Thus, by modifying the duration, mode, and magnitude of the ultrasonic power output, thermal injury and vascular perforation may be avoided. In vivo intra-arterial ultrasonic angioplasty of a canine chronic femoral fibrocellular occlusion was also performed. A preliminary in vivo study demonstrated feasibility of the percutaneous application of intra-arterial ultrasonic recanalization. Thus, ultrasonic energy appears to have potential as a method for ablation of occlusive atherosclerotic plaque.
Angiography↗
B cell activation in patients with active procainamide induced lupus.
Cellular immune abnormalities have been described in asymptomatic patients receiving procainamide therapy, but not in patients with active procainamide induced lupus. We tested patients with active procainamide lupus for evidence of T or B cell activation similar to that observed in idiopathic lupus. Symptomatic patients had a significant increase in spontaneous IgG synthesis, but T cells bearing activation markers were not significantly different from age matched controls. Our results demonstrate that patients with active procainamide lupus have evidence for B cell activation, similar to idiopathic lupus.
Aged↗
The effect of selective decontamination of the digestive tract with the addition of systemic cefotaxime on the aerobic faecal flora of mice.
The administration per-orally to mice of the non-absorbable antibiotics polymyxin E, tobramycin and amphotericin B resulted in the elimination of detectable aerobic gram-negative rods from the faecal flora without affecting the total viable aerobic count. The addition of parental cefotaxime to the regime caused a fall in the number of aerobic lactobacilli and an increase in the number of enterococci. The rise was associated with the translocation of viable enterococci to the mesenteric lymph nodes and the spleen. The changes induced by cefotaxime were reversed when the antibiotic was withdrawn. Following withdrawal of all antibiotics the total aerobic faecal flora increased to above normal levels, but there was no associated diarrhoea. Attempts to implant exogenous enterobacteria into the digestive tract resulted in only low level colonization both in treated mice and in control mice. These results may have implications for the use of this antibiotic regime for selective decontamination of the digestive tract in humans, particularly those who are immunocompromised.
Animals↗
Light paired with serotonin mimics the effect of conditioning on phototactic behavior of Hermissenda.
A conditioning procedure consisting of pairing-specific stimulation of the eyes and gravity-detecting statocysts in Hermissenda results in a long-term modification of normal positive phototactic behavior. The learning is expressed by a significant suppression of the initiation of locomotion in the presence of light. We now report that an analogue of the classical conditioning procedure, consisting of light paired with serotonin (5-HT) applied directly to the exposed circumesophageal nervous system of otherwise intact animals, mimics the effect of conditioning on long-term changes in phototactic behavior. The effect of the conditioning analogue on behavior shows some specificity with 5-HT since light paired with dopamine or octopamine does not significantly affect phototactic behavior. The conditioning analogue exhibits pairing specificity since unpaired light and 5-HT and 5-HT applied in the dark do not produce behavioral suppression. Animals that initially received unpaired light and 5-HT do show behavioral suppression after receiving paired light and 5-HT. These results indicate that light (the conditioned stimulus) paired with the putative transmitter of the unconditioned stimulus pathway (5-HT) is sufficient to produce long-term phototactic suppression.
Analysis of Variance↗
Intraoperative coronary angioscopy. Technique and results in the initial 58 patients.
Coronary angioscopy provides images of intravascular detail with greater than 0.2 mm spatial resolution and excellent contrast resolution. Using endoscopes of 1.25 to 1.8 mm outer diameter, we performed intraoperative angioscopy of the coronary arteries or saphenous vein grafts, or both, in 58 patients. Eighty-one native coronary arteries and 43 vein grafts were examined. A clear viewing field was created by infusion of crystalloid cardioplegic solution through the aortic root during cardiopulmonary bypass. Technical details crucial for obtaining high-quality images were as follows: sufficient coronary perfusion by cardioplegic solution to displace all blood; adequate intraluminal illumination; and high-quality fiberoptic and lens systems. Incomplete studies in approximately 14% of patients were related to failure to achieve these technical details and lack of scope steerability. In 30% of patients, previously unrecognized anatomic details were revealed by angioscopy. These included intimal flaps at the site of vein-to-artery anastomoses, atheromatous plaques with adherent thrombi, and hemorrhagic ulcerated plaques, not recognized on angiography. Although a coronary intimal flap developed proximal to the anastomosis during retrograde examination in two patients, no serious complications occurred as a result of the procedure. We conclude that intraoperative angioscopy is safe, provides novel information that may be clinically relevant, and has future potential for development of the techniques for coronary endarterectomy and intraoperative balloon and laser angioplasty.
Angina, Unstable↗
Digital quantification eliminates intraobserver and interobserver variability in the evaluation of coronary artery stenosis.
A leading problem with subjective interpretation of coronary angiography is high intraobserver and interobserver variability. Four experienced angiographers independently determined percent diameter narrowing of 36 stenoses using 3 methods: by subjective analysis of single-frame cine film images (film), by subjective analysis of digitized nonenhanced single-frame images (digital), and by using a semiautomated digital caliper quantification system (Corona). The reproducibility of interpretations was assessed by comparison of estimated intraclass correlation coefficients. Digital and Corona readings correlated well with subjective interpretation of film (r greater than 0.85 for both). In contrast to Corona, the angiographers systematically overestimated the magnitude of stenoses in the intermediate (50 to 75%) range. Corona markedly improved intraobserver (p less than 0.005) and interobserver (p less than 0.001) reproducibility. Corona less frequently misclassified individual observations than did film when categories of less than 50%, 50 to 75% and more than 75% diameter stenosis were used (3.7% vs 31.5%, p less than 0.001). Our results suggest that digitization of a coronary angiogram in a 512 X 512 matrix has no significant adverse effects on the perception and quantification of stenosis by angiographers. Additionally, automatic measurement of coronary stenosis has 2 major advantages: It is accurate compared with a group of experienced angiographers and for the practical purpose of clinical decision-making, it eliminates intraobserver and interobserver variability.
Angiography↗