Biomedical subjects
Publications and source records attributed to J Forrester.
It is well known that polyarticular joint diseases such as rheumatoid arthritis, HLA-B27-associated arthritis and Borreliosis can be associated with eye diseases, such as uveitis, scleritis and keratitis. However, the mechanisms underlying the involvement of these tissues remain unclear. A recent meeting examined the immunoregulation of the eye and the joint in an attempt to determine their similarities and differences.
Within the first year, 15-20% of coronary artery saphenous bypass vein grafts (SVGs) occlude because of thrombosis or progressive intimal hyperplasia. One potential new strategy to reduce this complication would be to introduce antithrombotic or antiproliferative genes in vein grafts before implantation. The success of this approach requires an efficient DNA delivery system. In the present study we tested the feasibility of using adenovirus-transferrin/polylysine-DNA complexes (TfAdpl/DNA) to achieve high-efficiency gene transfer into vascular interposition vein grafts. All studies used the Escherichia coli LacZ (beta-galactosidase [beta-Gal]) reporter gene under the control of the cytomegalovirus (CMV) earlier promoter and enhancer (pCMV/LacZ). Autologous rabbit jugular vein segments were incubated ex vivo for 60 min in a solution of TfAdpl/DNA complexes (1.2 x 10(10) biotinylated adenovirus particles, 2,430 ng of streptavindylated polylysine. 10 micrograms of plasmid DNA, and 9 micrograms of transferrin-polylysine per ml), and then reimplanted across the ligated right carotid artery. Control veins were incubated in TfAdpl solution in which DNA was omitted. A total of six grafts were treated with TfAdpl/DNA, and two grafts were treated with TfAdpl. Veins were harvested 3 (n = 3) and 7 (n = 3) days later and beta-Gal activity was determined by X-Gal chromogen staining. All six TfAdpl/DNA-treated grafts stained intensely blue, whereas control grafts were negative. Microscopic examination of serial sections revealed intracellular blue granules consistent with beta-Gal activity to be present in all of the endothelial cells and in numerous medial and advential cells.(ABSTRACT TRUNCATED AT 250 WORDS)
One-trial conditioning of Hermissenda produces short- and long-term enhancement of generator potentials in identified type B-photoreceptors. The induction of short-term enhancement is blocked by kinase inhibitors and down-regulation of protein kinase C. We now report that established short- and long-term enhancement produced by one-trial conditioning is not reversed by the kinase inhibitors H-7 or sphingosine. These results indicate that persistent protein kinase C activity is not required in the maintenance or expression of enhancement.
Retinal exudates are a common manifestation of vascular damage in a variety of retinal diseases. We have used computerized image analysis to detect and measure the area of exudates from digitized colour fundus slides of patients with diabetic retinopathy and have assessed the repeatability, reproducibility, and accuracy of the technique. The analysis was entirely independent of the operator apart from choice of the region to be analysed. The coefficient of variation for repeatability was between 3% for large areas of exudate and 17% for small areas of exudate. The reproducibility was also within this range. Sensitivity was between 61 and 100% (mean 87%). False-positives were observed in 5 of 30 regions analysed, and these could have been eliminated by using more stringent criteria for selection of images for analysis. Time taken for the analysis was approximately 3 min.
1. The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. Previous research has shown that one-trial conditioning, consisting of light paired with serotonin (5-HT) results in short- and long-term enhancement of light-elicited generator potentials in identified type B-photoreceptors. Recent evidence suggests that 5-HT exerts its effects on the induction of short-term enhancement by activation of protein kinase C (PKC), a Ca(2+)-activated and phospholipid-dependent protein kinase. However, the contribution of protein kinases in general, and specifically PKC in long-term enhancement has not been established. 2. The protein kinase inhibitors H-7 and sphingosine blocked the induction of short-term enhancement when applied before one-trial conditioning. However, the conditions that are sufficient to block the induction of short-term enhancement do not block long-term enhancement. Sphingosine and H-7 do not block the induction and expression of long-term enhancement when applied before one-trial conditioning. 3. Pretreatment before conditioning with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which leads to down-regulation of PKC, also did not block long-term enhancement. Down-regulation by itself did not produce enhancement, although the transient peak of light-elicited generator potentials was reduced by pretreatment with TPA. 4. The results suggest that the induction of short- and long-term enhancement involve parallel processes, and thus the expression of long-term cellular plasticity produced by one-trial conditioning does not depend on the induction or expression of short-term enhancement.
Explore the source record for details and available documents.
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.
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.
Explore the source record for details and available documents.
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.
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.
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.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
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.
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.
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.