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R S Lord

Publications and source records attributed to R S Lord.

At least 55 records · Page 3Linked to original sources
PubMed1999

Ultrastructural recognition of dendritic cells in the intimal lesions of aortas of chickens affected with Marek's disease.

The present study was undertaken to determine whether dendritic cells contributed to the intimal abnormalities seen in the aortas of chickens infected with Marek's disease. Semithin sections were used to select aortic segments in which the intima was thickened by lymphocytic infiltrates. Ultrathin sections were then examined. Intermingled with lymphocytes within the intimal thickenings were cells with an appearance typical of dendritic cells including long processes and a unique tubulovesicular system. In these cellular processes the tubulovesicular system was hypertrophied with the tubular cisterns characteristically forming concentric cyclical layers. Our observations show that dendritic cells are present in the aortic lesions of Marek's disease and are presumably involved in related immune mechanisms.

Animals↗
PubMed1999

Structural features of cell death in atherosclerotic lesions affecting long-term aortocoronary saphenous vein bypass grafts.

Aortocoronary saphenous vein bypass grafts fail because of structural pathologies (thrombosis, intimal hyperplasia and atherosclerosis) within the 'arterialized' vein leading to graft stenosis. This study examined structural characteristics of atherosclerotic alterations in long-term aortocoronary artery saphenous vein bypass grafts with particular attention to the features of cell death in atherosclerotic lesions. Stenotic vein grafts were obtained from 10 patients at redo coronary artery bypass grafting operations. All the grafts were affected by histological abnormalities, with eight out of ten grafts showing evidence of atherosclerotic alterations in the intimal hyperplastic layer. Areas containing foam cells were examined by electron microscopy. Cells with cytoplasmic lipid accumulations were characterized by varying degrees of chromatin condensation, fragmentation or dispersion, by focal areas of oedema and vacuolisation of their cytoplasm, and by plasmalemmal destruction. Some lipid-filled cells exhibiting signs of destruction contained myofilaments and basal membrane fragments, allowing them to be identified as smooth muscle cells. Macrophage foam cells were found to have undergone similar destruction. No cells showing nuclear degeneration were observed to have intact cytoplasmic organelles. Neither were apoptotic bodies identified, but necrotic remnants were frequently seen. The results suggest that cell death in atherosclerotic lesions affecting aortocoronary artery saphenous vein bypass grafts occurs through oncosis rather than by apoptosis.

Adult↗
PubMed1999

Ultrastructural identification of cells with dendritic cell appearance in atherosclerotic aorta of apolipoprotein E deficient mice.

The present electron microscopic study was undertaken to see whether cells with a dendritic cell appearance accumulate in atherosclerotic lesions of apolipoprotein E (apoE) deficient mice. Atherosclerotic aortas from 7 eight-month old apoE deficient mice were examined. In atherosclerotic plaques as well as in the underlying media and adventitia, cells with a dendritic cell appearance including the presence of a unique tubulovesicular system were detected. The tubulovesicular system was most hypertrophied in their cellular processes where the continuous cisterns sometimes formed circular structures. The cells containing the tubulovesicular system lacked lysosomes and phagolysosomes and their cytoplasm was free of lipid inclusions. The present observations suggest that dendritic cells are involved in apoE deficient mouse atherosclerosis. ApoE deficient mice might be a useful model for investigating functions of dendritic cells in atherogenesis.

Animals↗
PubMed1998

Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions.

OBJECTIVE: We previously demonstrated that vascular dendritic cells (VDCs) are present in the intima of large arteries and that their numbers are increased in atherosclerotic lesions. This study was undertaken to determine whether VDCs are involved in immune-mediated reactions in atherogenesis. METHODS: Specimens of carotid artery and aorta were obtained at operation. VDCs were identified with anti-CD1a or with S-100. Co-localisation of VDCs with different intimal cells, including T-cells and macrophages, was studied using a double immunostaining procedure. In areas where the co-localising cells were detected, the peculiarities of expression of HLA-DR, ICAM-1, VCAM-1 were examined. RESULTS: In all the atherosclerotic plaques, VDCs were seen in contact with T-cells, but these co-localising cells were irregularly distributed and were mainly found in zones of neovascularisation containing inflammatory infiltrates. In other areas, T-cell/VDC co-localisation was rarely detected but VDCs were often found in contact with macrophages. VDCs were detected also in the media beneath atherosclerotic lesions and in the adventitia, where they were mostly around vasa vasorum, especially in areas exhibiting signs of acute inflammation. In these areas VDCs expressed ICAM-1, VCAM-1 and were in contact with T-cells. In both plaques and in the adventitia, the areas with co-localising VDCs and T-cells corresponded to the areas with HLA-DR expression. CONCLUSIONS: The results suggest that VDCs are involved in T-cell activation in atherogenesis. There are two regions within the arterial wall where VDC/T-cell co-localisation mostly occurs, namely, in zones of neovascularisation containing inflammatory infiltrates located within atherosclerotic lesions, and in areas with inflammatory infiltrates around vasa vasorum in the adventitia. Possibly, some intimal VDCs migrate through the media and adventitia to adjacent lymph nodes where they present atherosclerosis associated antigens. We also speculate that VDC/macrophage contacts are essential in processing immune information in atherogenesis.

Adult↗
PubMed1998

The cell adhesion molecule E-cadherin is widely expressed in human atherosclerotic lesions.

OBJECTIVE: Various cell adhesion molecules are expressed in atherogenesis and the significance of their involvement in atherosclerotic lesion formation is well appreciated. In the present work, we examined whether the Ca(2+)-dependent cell adhesion molecule E-cadherin is also involved in atherogenesis. METHODS: Specimens of carotid artery and aorta were obtained at operation. Expression of E-cadherin was studied by an immunohistochemical method. The nature of E-cadherin-expressing cells was examined by comparative analysis of consecutive sections and by a double immunostaining procedure. An immunohistochemical approach was also applied to examine how the accumulation of oxidised low density lipoproteins (LDL) by intimal cells is associated with E-cadherin expression. RESULTS: No E-cadherin+ cells were found in normal non-atherosclerotic intima but E-cadherin+ cells were present in 96% of the atherosclerotic lesions. In atherosclerotic intima, E-cadherin was expressed by intimal cells showing varying degrees of transformation into foam cells. These E-cadherin+ cells also contained oxidised LDL in their cytoplasm. Differing numbers of CD68+ foam cells (15% to 60%) expressed E-cadherin but all the CD68+ macrophages without signs of transformation into foam cells were negative for E-cadherin. Neither smooth muscle cells nor foam cells of smooth muscle cell origin (smooth muscle alpha-actin+) were found to be positive for E-cadherin. T-cells (CD3+) and endothelial cells (von Willebrand factor+) were also negative for E-cadherin. Only a few vascular dendritic cells (S-100+) expressed E-cadherin and their expression was weak. We also found that a large proportion (40% to 85%) of E-cadherin+ cells did not stain with any cell-type specific markers. CONCLUSIONS: The finding that E-cadherin is expressed in atherosclerotic lesions expands our knowledge of cell adhesion molecules involved in atherogenesis. That E-cadherin is expressed in intimal cells transforming into foam cells suggests that lipid accumulation might be associated with the alteration and reorganisation of cell-to-cell interactions in atherogenesis. The present observations might assist in understanding the mechanisms associated with intracellular lipid accumulation.

Adult↗
PubMed1998

Detection of vascular dendritic cells accumulating calcified deposits in their cytoplasm.

The distribution of calcified microdeposits in non-atherosclerotic intima of the human aorta was studied by electron microscopy. Aortic specimens were obtained during aortic reconstruction and were embedded in Lowicryl resin. Non-stained ultrathin sections were analysed using an electron microscope equipped with an energy-dispersive X-ray microanalyser. Subsequent staining of these ultrastructural sections with lead citrate allowed us to view the tissue structures and allowed the precise location of calcified deposits in the intimal tissue to be determined. Calcium-containing microstructures were found in the extracellular matrix of the intima but, occasionally, calcium-containing microdeposits were also seen in the cytoplasm of intimal cells. Cisterns of a tubulovesicular system which is uniquely developed in cells from the dendritic cell family were detected in the calcium-containing intimal cells, which enabled these calcium-accumulating cells to be identified as a phenotype of vascular dendritic cells. These modified vascular dendritic cells might be the 'calcifying vascular cells' described previously by others.

Adult↗
PubMed1998

Immunophenotypic analysis of the aortic aneurysm wall suggests that vascular dendritic cells are involved in immune responses.

OBJECTIVE: Inflammatory infiltrates similar to those in atherosclerotic plaques are prominent in the abdominal aortic aneurysm wall. Antigen presenting vascular dendritic cells are present in both early and advanced atherosclerotic lesions but their possible participation in abdominal aortic aneurysms has not been previously examined. This study reports the presence of vascular dendritic cells in abdominal aortic aneurysms and their participation in immune responses. METHODS: Samples of the anterior wall were collected from 18 atherosclerotic infrarenal abdominal aortic aneurysms ranging in diameter from 5-8 cm. All the patients were operated upon electively and no ruptured or rapidly expanding abdominal aortic aneurysms were included. Specimens were immediately frozen or fixed in 10% buffered formalin. Vascular dendritic cells were identified with anti-CD1a or with S-100. T cells and T cell subpopulations were identified with anti-CD3, anti-CD4 and anti-CD8. B cells were studied with anti-CD20. Analyses were carried out in sets of consecutive parallel sections immunostained with these antibodies and double immunostaining included different combinations of antigens such as CD1a/CD3, S-100/CD4, S-100/CD8. RESULTS: Most inflammatory infiltrates were found in the adventitia. These infiltrates contained B cells (CD20+) and T cells (CD3+) with their CD4+ and CD3+ cell subpopulations. In the aneurysm wall, CD1a+/S-100+ cells exhibiting dendritic appearance were detected and double immunostaining demonstrated that these vascular dendritic cells contained different lymphocyte populations including CD3+, CD4+, CD8+ and CD20+ cells. In some inflammatory infiltrates, B cells (CD20+) represented the predominant cell population (60-80%). Double immunostaining demonstrated that, in these infiltrates, vascular dendritic cells contacted CD20+ cells. CONCLUSIONS: Vascular dendritic cells are involved in immune reactions in the aneurysm wall, and this process mostly occurs in the adventitia. Vascular dendritic cells contact both T cells and B cells, suggesting that these vascular dendritic cells differ from other dendritic cells, subtypes of which associate with T cells (Langerhans cells, interdigitating cells) and B cells (follicular dendritic cells).

Aorta↗
PubMed1998

Small vessel ischaemia induced by microbead embolization in the sheep hind limb.

BACKGROUND: Peripheral ischaemia may be caused by small vessel disease but there has been no satisfactory experimental model for studying this condition. We have developed a model in which microbeads are embolized to the distal vascular bed of a sheep. This model induces ischaemia proportional to the volume of microbead infusion and allows the pathophysiology and therapy of small vessel occlusion to be studied. METHODS: Gradual reduction of femoral artery blood flow by 50% and 75% in unilateral hind limbs of eight sheep was achieved by slow introduction of latex microbeads (mean size = 400 microns) into the peripheral vascular bed. The other hind limb served as a control. Measurements of blood flow, subcutaneous temperature and arterial and venous blood gases were recorded in both hind limbs after each level of flow reduction. Angiography confirmed small vessel occlusion. Muscle samples were analysed for ultrastructural changes by transmission microscopy. RESULTS: A linear correlation was found between the amount of microbeads infused and the reduction in the blood flow. Significant subcutaneous temperature and venous pO2 changes were observed in the embolized limb at both 50% and 25% flow levels compared to baseline (P < 0.05, ANOVA). Angiography demonstrated abrupt cut-off images of the small vessels. Transmission microscopy showed graded levels of muscle cell damage from ischaemia. CONCLUSIONS: Latex microbead embolization induces reproducible controlled small artery occlusion. The degree of outflow obstruction and the extent of ischaemia can be varied by delivering measured quantities of microbeads. This model should be useful for studying the pathophysiology of ischaemia and for assessing the efficacy of treatment, especially the use of pharmacological agents.

Animals↗
PubMed1997

Incorporation and localisation of ganglioside GM3 in human intimal atherosclerotic lesions.

Immunohistochemical examination showed that sections of intimal atherosclerotic plaques contained cells and cell clusters as well as areas of extracellular matrix specifically stained with antibodies against ganglioside GM3. No immunohistochemical staining was observed in areas bordering the plaques where there was no histological evidence of atherosclerosis. To determine whether the ganglioside GM3 deposits in the intimal plaques derived directly from plasma or were synthesised by intimal cells. intimal plaque and plasma LDL were assayed for ganglioside GM3 fatty acid composition. This assay showed that more than 50% of the fatty acids of GM3 isolated from both atherosclerotic and normal intima are either minor fatty acids or those absent from LDL GM3. We conclude that the GM3 deposits present in intimal plaque arise in intimal cells and do not derive from plasma LDL.

Arteriosclerosis↗
PubMed1997

Artery wall damage and platelet uptake from so-called atraumatic arterial clamps: an experimental study.

A 'traumatic' clamps are routinely used to control arteries during reconstruction, but little is known about the arterial damage caused and the effects on platelet uptake. This experiment used sheep carotid arteries to correlate the degree of histologic damage observed with the level of indium-111-labelled platelet uptake in clamped arterial segments. Scanning electron microscopy and light microscopy enabled three degrees of injury to be recognized. In mild injuries, endothelial cell orientation was changed but local platelet uptake was little different from controls. In moderate injuries, the endothelial cells directly squeezed by the clamp were morphologically altered, superficial fissures developed which extended into the media, and local platelet uptake was usually increased. Severe injuries caused extensive endothelial cell desquamation, formation of deep cavities in the media and increased platelet uptake (mean 5.51 times that of control). Platelet uptake at the site of clamp application was not significantly different from non-clamped carotids for mild injuries. However, the increased platelet uptakes for moderate (P = 0.007) and severe (P = 0.005) injuries were statistically significant when compared with non-clamped control arterial segments.

Animals↗
PubMed1997

The effect of arterial clamp duration on endothelial injury: an experimental study.

BACKGROUND: Arterial clamp-related endothelial damage was investigated in an animal model to quantify the surface area of endothelial disruption. The influence of the duration of clamp application on this damage was evaluated. METHODS: Four identical angled DeBakey vascular clamps were applied on each of eight carotid arteries in four heparinized adult sheep for durations of 15, 30, 45 and 60 min. The applied clamping forces were measured and kept constant. After the last clamp was removed, the areas of endothelial loss were identified by in vivo staining with Evan's blue dye. The vessels were excised and the blue stained areas measured by computer-assisted analysis. The morphological appearance of the specimens was assessed by scanning electron microscopy. RESULTS: Endothelial damage following clamping for 15 min (10.6 +/- 4.3 mm2) was significantly less than for 30 min (19.0 +/- 4.7 mm2), 45 min (19.8 +/- 4.6 mm2) and 60 min (20.4 +/- 4.9 mm2, P = 0.005), but there were no significant differences between the areas of endothelial loss observed for 30, 45, and 60 min. These results corresponded to the damage seen using scanning electron microscopy, which showed partial disruption of endothelium at 15 min compared to more complete destruction at longer durations. CONCLUSIONS: Evan's blue staining combined with computer-assisted surface area measurement is an accurate method for quantifying endothelial damage. The extent of damage caused by vascular clamps is partly time-dependent, being less for 15 min than for 30 min of clamping, but not significantly increasing for durations greater than 30 min.

Animals↗
PubMed1997

Structural peculiarities of vascular dendritic cell tubulovesicular system in human atherosclerotic aorta.

The principal function of vascular dendritic cells has been suggested to be antigen processing/presentation but how this might occur is not clear. To find out whether the organisation of vascular dendritic cells might allow them to internalise antigens, we used electron microscopy to examine their fine cytoarchitectonics. Tubular and vesicular structures were observed to form continuous nets through which extracellular molecules might gain access to lysosomes. This suggests that vascular dendritic cells might be able to degrade antigens using the same mechanisms as occur in macrophages. We also speculate that antigen processing might be different between type I vascular dendritic cells which possess a hypertrophied tubulovesicular system and type II vascular dendritic cells where the tubulovesicular system is less prominent. The present work indicates that the tubulovesicular system is functionally associated with the extracellular space. This connection with the extracellular space through the system of cisterns and vesicles can allow the transport of different substances entering the cistern nets.

Aorta↗
PubMed1996

Non-invasive testing for cerebrovascular disease.

Selecting the appropriate investigation for diagnosing occlusive cerebrovascular disease depends on the availability, cost, accuracy, invasiveness and the purpose of the test. Intraarterial digital subtraction angiography remains the gold standard, but for accuracy the stenosis should be measured rather than estimated. Duplex ultrasonography is almost as accurate and can additionally analyse plaque morphology. Of 2651 duplex tests carried out in our laboratory, 12.2% were for reversible ischaemic attacks, 2.7% for amaurosis, 12.1% for cervical bruit and 4.3% for vertebrobasilar ischaemia. Duplex within 30 days of operation was carried out on 607 patients (22.9%) and surveillance on 1000 others (37.7%). Asymptomatic carotid stenosis > 60% should be confirmed by intra-arterial digital subtraction angiography, magnetic resonance angiography or spiral computed tomography angiography. For typical transient ischaemic attacks, duplex or angiography alone is adequate but when the clinical presentation is atypical, a confirming test is required. Routine preoperative brain computed tomography is not cost-effective, being equivalent to US$ 4300-11840 per perioperative stroke in our institution. Postoperative surveillance is justified, costing only US$ 505 per patient over 4 years.

Angiography, Digital Subtraction↗
PubMed1996

Myocardial ischaemia, infarction and cardiac-related death following carotid endarterectomy: risk assessment by thallium myocardial perfusion scan compared with clinical examination.

Risk factors in 402 patients undergoing 447 carotid endarterectomies were reviewed to see whether the presence of coronary artery disease before operation influenced the likelihood of perioperative cardiac complications. A second aim of the study was to assess whether myocardial thallium scintigraphy was valuable for preoperative assessment. Fourteen patients developed postoperative cardiac complications, six (1.3%) of which were fatal. Four of these deaths occurred in 60 patients undergoing combined carotid-coronary revascularization (6.6%). In 387 carotid endarterectomies without simultaneous coronary revascularization, there were two deaths from myocardial infarcts (0.5%). These fatalities and other cardiac complications occurred in 204 patients with preoperative clinical or ECG evidence of coronary artery disease. In 198 patients with no preoperative evidence of coronary disease there were no fatalities and only one patient with reversible postoperative myocardial ischaemia (0.4%). It is concluded that carotid endarterectomy under general anaesthesia is unlikely to be followed by cardiac complications when there is no preoperative evidence of coronary artery disease. When coronary disease is detected before operation, postoperative cardiac complications occur after 5.6% of operations, including 0.9% fatalities. When coronary artery disease is severe enough to warrant combined carotid-coronary reconstruction, the perioperative mortality rate was 6.6%, all the deaths being cardiac-related. When myocardial thallium scintigraphy was normal, postoperative cardiac complications did not occur.

Carotid Stenosis↗
PubMed1996

Langhans cells of human arterial intima: uniform by stellate appearance but different by nature.

The stellate cells in human arterial intima known as Langhans cells were investigated. Arterial specimens were obtained during carotid endarterectomy and aortic reconstruction and included atherosclerotic lesions as well as areas of the adjacent normal appearing arterial wall. Following immunohistochemical and electron microscopic analysis, most of the stellate cells were found to inhabit the elastic-hyperplastic layer of the intima in the normal arterial wall but in atherosclerotic lesions, stellate cells were distributed throughout all intimal layers. Immunohistochemical examination revealed that different types of intimal cells, including smooth muscle cells (HHF-35; smooth muscle alpha-actin +) and vascular dendritic cells (CD1a+, S-100+), exhibited a typical stellate appearance but the cell processes of macrophages (HAM56+, CD68+) were too short for macrophages to be considered as stellate. No other intimal cells formed processes which could be detected under immunohistochemical examination. In atherosclerotic lesions, some smooth muscle cells transforming to foam cells retained their stellate shape. Smooth muscle cells interacted with each other through gap junctions while other intimal cells including vascular dendritic cells contacted each other without forming any specialized structures. We conclude that Langhans cells comprise two histological types of intimal cells, namely, smooth muscle cells and vascular dendritic cells.

Antibody Specificity↗
PubMed1996

VCAM-1 expression and network of VCAM-1 positive vascular dendritic cells in advanced atherosclerotic lesions of carotid arteries and aortas.

This study was undertaken to determine whether vascular dendritic cells (VDCs) display VCAM-1 in atherosclerotic lesions. Specimens of carotid artery and aorta were obtained at operation. All the plaques contained VCAM-1+ cells, but VCAM-1 immunoreactivity was irregularly distributed being mainly associated with the zones of neovascularisation in the base of the atherosclerotic plaques. Vascular dendritic cells were identified with DAKO-CD1 a. Alternative parallel sections were stained with either anti-CD1 a or anti-VCAM-1. By comparison of consecutive parallel sections the CD1a+ vascular dendritic cells were located separate from other intimal cells. In some areas networks formed by VCAM-1+ vascular dendritic cells were observed suggesting that cellular networks may mediate a local immune response in atherosclerotic lesions. We speculate that VCAM-1 is involved in the formation of cell-to-cell contacts of vascular dendritic cells in atherogenesis.

Adult↗