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Biomedical subjects

R S Lord

Publications and source records attributed to R S Lord.

At least 19 recordsLinked to original sources
PubMed2001

Phenotype determination of anti-GM3 positive cells in atherosclerotic lesions of the human aorta. Hypothetical role of ganglioside GM3 in foam cell formation.

Earlier we reported that atherosclerotic plaques contain cells which were specifically and very intensively stained with anti-GM3 antibodies although no GM3 positive cells were detected in the normal non-diseased arterial intima. Because of their lipid inclusions, GM3 positive cells in atherosclerotic lesions seemed to be foam cells but their origin needed clarification. Using an immunohistochemical technique in the present work, we showed that some of these foam cells contained CD68 antigen. However, the most intense accumulation of GM3 occurred in the areas composed of foam cells which did not stain with any cell type-specific antibodies, including antibodies to macrophages (anti-CD68) and smooth muscle cells (anti-smooth muscle alpha-actin), perhaps, because the cell type-specific antigens were lost during the transformation of intimal cells into foam cells. Ultrastructural analysis of the areas where foam cells overexpressed GM3 demonstrated that some foam cells lacked both a basal membrane and myofilaments but contained a large number of secondary lysosomes and phagolysosomes, morphological features which might indicate their macrophage origin. Other foam cells contained a few myofilaments and fragments of basal membrane around their plasmalemmal membrane, suggesting a smooth muscle cell origin. These observations indicate that accumulation of excessive amounts of GM3 occurs in different cell types transforming into foam cells. We suggest that up-regulation of GM3 synthesis in intimal cells might be an essential event in foam cell formation. Shedding of a large number of membrane-bound microvesicles from the cell surface of foam cells was observed in areas of atherosclerotic lesions corresponding to extracellular GM3 accumulation. We speculate that extracellularly localised GM3 might affect the differentiation and modification of intimal cells in atherosclerotic lesions.

Adult↗
PubMed2001

Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss.

Paraganglioma (PGL) is a rare disorder characterized by tumors of the head and neck region. Between 10% and 50% of cases of PGL are familial, and the disease is autosomal dominant and subject to age-dependent penetrance and imprinting. The paraganglioma gene (PGL1) has been mapped to 11q22.3-q23, and recently germline mutations in the SDHD gene have been identified. The SDHD region contains another gene, DPP2/TIMM8B, the homolog of which causes dystonia and deafness seen in Mohr-Tranebjaerg syndrome. Using four PGL pedigrees, two of which exhibit coinheritance of PGL and sensorineural hearing loss or tinnitus, analysis of 14 microsatellite markers provided support for linkage to the PGL1 locus. Sequence analysis identified novel mutations in exon 1 and exon 3 of the SDHD gene, including a novel two base pair deletion in exon 3 creating a premature stop codon at position 67; a novel three base pair deletion in exon 3 resulting in the loss of Tyr-93; a missense mutation in exon 3 resulting in the substitution of Leu-81 for Pro-81; and a novel G-to-C substitution in exon 1 resulting in the substitution of Met-1 for Ile-1. No base changes were detected in the DPP2/TIMM8B gene. There was no apparent loss of heterozygosity at the site of the SDHD mutations. However, RT-PCR analysis of tumor samples showed monoallelic expression of the mutant (paternal) allele as expected for imprinting. This has not previously been shown for this disorder. The inheritance and expression of the SDHD gene is consistent with the PGL1 gene being subject to genomic imprinting.

Adolescent↗
PubMed2001

Ernst Ferdinand Sauerbruch: rise and fall of the pioneer of thoracic surgery.

Ferdinand Sauerbruch (1875-1951) was a pioneer of thoracic and cardiac surgery and is undoubtedly one of the twentieth century's most outstanding surgeons. Before 1904 operations on the thorax met with fatal complications due to pneumothorax. Sauerbruch developed a pressure-differential chamber that maintained normal respiration and enabled safe operations to be undertaken on the thorax. Together with von Mikulicz, he initiated intrathoracic operations and later developed various surgical procedures on the mediastinum, lungs, pericardium, heart, and esophagus. The simple yet effective techniques of positive-pressure ventilation replaced the expensive, cumbersome negative-pressure chamber. Sauerbruch's latter years were marred by dementia that adversely affected his personality, intellect, and capacity as a surgeon. The unjustifiable toll of increasing patient morbidity and mortality forced authorities to dismiss him in 1949. He died at the age of 76 in Berlin. After almost a century since the advent of the first safe thoracic surgery, the advances in technique and technology have been enormous. A great deal is owed to the inspiration and contributions of Ferdinand Sauerbruch.

Equipment Design↗
PubMed2001

Vascular-associated lymphoid tissue (VALT) involvement in aortic aneurysm.

Vascular-associated lymphoid tissue (VALT) consisting of accumulations of immunocompetent and antigen presenting cells has recently been recognised in the arterial wall. In this study, we investigated the involvement of VALT in immune responses in abdominal aortic aneurysms (AAAs). Tissue samples were collected during operations from 31 patients with atherosclerotic infrarenal abdominal aortic aneurysms ranging in diameters from 5 to 8 cm. The specimens were immediately frozen and examined using single and double immunohistochemical staining. T-cell subpopulations, B-cells, dendritic cells and macrophages were identified using cell type specific antibodies. Cell contacts were examined by electron microscopy. Most inflammatory infiltrates were found in the adventitia. T-cells were the predominant cell type in a majority of inflammatory infiltrates but in seventeen cases, typical lymphoid follicles with B-cells forming germinative centres were also observed. In eight cases, the lymphoid follicles aggregated in lymph node-like structures. Dendritic cells were present within all inflammatory infiltrates and contacted lymphocytes. The present observations show that in aortic aneurysm, VALT is involved in immune responses and its activation mostly occurs in the adventitia. The formation of lymphoid follicles and lymph node-like structures in the adventitia suggests that VALT might locally serve the entire complex of both cellular and humoral immune responses in the aneurysmal wall.

Aged↗
PubMed2001

Immunohistochemical and ultrastructural evidence that dendritic cells infiltrate stenotic aortocoronary saphenous vein bypass grafts.

We earlier speculated that antigen-presenting dendritic cells may be involved in the immune reactions leading to saphenous vein bypass graft failure. The purpose of this study was to confirm whether dendritic cells are present in stenotic human saphenous vein bypass grafts. Segments of stenotic saphenous vein grafts were explanted from 14 patients at re-do bypass operation and ten normal saphenous veins were harvested during femoro-popliteal grafting. Sections of specimens were analysed using cell type specific antibodies to identify dendritic cells (CD1a, S-100), T-lymphocytes (CD3), macrophages (CD68), smooth muscle cells (alpha-SMA) and endothelial cells (FVIII). Dual immunostaining, confocal immunofluorescent laser scanning microscopy and electron microscopy were used. Stenotic grafts showed structural alterations of intimal hyperplasia and varying degrees of atherosclerotic degeneration. No cells expressing CD1a and S-100 were observed in the intima and media of normal saphenous veins. Cells expressing these antigens were present around areas of medial neovascularization and within intimal atherosclerotic lesions in saphenous vein bypass grafts. Electron microscopy demonstrated the presence of cells containing a well-developed tubulovesicular system which is unique to cells from the dendritic cell family. Double immunohistochemistry and confocal immunofluorescent microscopy revealed the co-localization of T-lymphocytes with dendritic cells. Dendritic cells are present in stenotic saphenous vein bypass grafts. Dendritic cells may be responsible for antigen presentation and modulation of immune reactions in accelerated graft atherosclerosis through their interaction with T-lymphocytes.

Adult↗
PubMed2001

Colonisation of prosthetic grafts by immunocompetent cells in a sheep model.

The present study examined the distribution of immunocompetent cells in synthetic vascular grafts in an experimental sheep model. Sixty-two adult Merino sheep underwent synthetic patch closure of a longitudinal arteriotomy in the left common carotid artery. The synthetic patch materials used were gelatin sealed Dacron (n=10), fluoropassivated Dacron (n=10), Fluoropassiv (n=12), polyurethane (n=10), expanded polytetrafluoroethylene (n=10) and carbon-lined expanded polytetrafluoroethylene (n=10). The sheep were sacrificed after four weeks when the prosthetic patches were harvested and fixed in 10% neutral buffered formalin. Transverse sections were taken along the graft and paraffin embedded. Serial sections were stained with cell type specific antibodies to identify T-lymphocytes (CD3(+)), dendritic cells (S-100(+)), endothelial cells (von Willebrand factor(+)) and smooth muscle cells (smooth muscle alpha-actin(+)). All six graft types contained CD3(+) and S-100(+) cells in the neointima, within the synthetic matrix and in the perigraft layer. Three different tissue responses to synthetic materials were observed and the grafts were classified accordingly into three groups: (1) gelatin sealed Dacron, fluoropassivated Dacron and Fluoropassiv; (2) expanded polytetrafluoroethylene and carbon-lined expanded polytetrafluoroethylene; (3) polyurethane. The three synthetic materials in Group 1 showed almost identical reactions with least accumulation of immunocompetent cells within the synthetic material but greater accumulation of immuno-inflammatory infiltrates in the perigraft vascular tissue. In this group, new vessels penetrated into the synthetic material and there was prominent formation of foreign body (giant) cells. Group 2 showed greater accumulation of immunocompetent cells within the synthetic material itself but only sparse immuno-inflammatory infiltrates in the perigraft tissue. Group 3 showed a high degree of inflammatory response within both the synthetic material and the perigraft vascular tissue. These observations demonstrate that immunocompetent cells colonise the synthetic matrix of grafts and accumulate in the perigraft tissue, but inflammatory responses vary in different graft types.

Animals↗
PubMed2001

Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts.

This study aimed to investigate the features of cell death occurring in aortocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibodies to Bcl-2, Fas, BAX, p53 and CPP32. Cells undergoing DNA fragmentation were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). DNA synthesis was investigated using the antibody to proliferating cell nuclear antigen (PCNA). Ultrastructural features of cell death were examined by electron microscopy. Anti-apoptotic (Bcl-2) and pro-apoptotic (Bax, p53, CPP32 and Fas) proteins were expressed throughout the graft wall, but marked differences in the characteristics of cell death were noted between atherosclerotic and non-atherosclerotic areas of the intima. In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical features of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic proteins showed no correlation with TUNEL. In contrast, in non-atherosclerotic areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and pro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In atherosclerotic areas, non-atherosclerotic intimal areas, and in the underlying media, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastructurally, apoptotic bodies and features of necrosis were observed in non-atherosclerotic areas of grafts. The present observations indicate that in atherosclerotic areas, cell death occurs mainly by necrosis, while in non-atherosclerotic areas, cell death occurs by both necrosis and apoptosis. An imbalance between DNA fragmentation and DNA synthesis may contribute to graft instability and failure.

Aged↗
PubMed2001

CD40 co-stimulatory molecule expression by dendritic cells in primary atherosclerotic lesions in carotid arteries and in stenotic saphenous vein coronary artery grafts.

We have previously identified dendritic cells in the intima of human large arteries and stenotic vein coronary bypass grafts. The mechanisms by which these dendritic cells might regulate immune responses in atherosclerotic lesions and stenotic vein grafts are unknown. The aim of the present study was to investigate whether dendritic cells in carotid plaques and in stenotic aortocoronary vein grafts express an immunoregulatory molecule CD40. Segments of wall from eight carotid arteries and three stenotic aortocoronary saphenous vein grafts were obtained at operation. CD40+ cells were detected in all specimens of both occluded and stenotic grafts and carotid plaques. Although CD40+ cells of various cell types were intermingled in most areas within the plaques and stenotic grafts, there were sites where CD40+ cells were located in small groups. Consecutive sections demonstrated that a small population of CD40+ cells stained positively for S100. These CD40+/S100+ cells were clustered within the intima but were also found in the media and adventitia. This suggests that dendritic cells, which accumulate within vessels affected by atherosclerosis and graft disease, express CD40 co-stimulatory molecule. The expression of CD40 molecule on the dendritic cells may be important in regulating T cell responses within atherosclerotic plaques and stenotic vein grafts.

CD40 Antigens↗
PubMed2001

Expression of vascular endothelial growth factor in aortocoronary saphenous vein bypass grafts.

Neovascularisation is a prominent feature of long-term aortocoronary saphenous vein bypass grafts but mechanisms involved in the formation of neovessels have not been previously studied. Vascular Endothelial Growth Factor (VEGF) is an important angiogenic factor that induces migration and proliferation of endothelial cells, enhances permeability and modulates thrombogenecity. This study investigated the expression of VEGF in aortocoronary saphenous vein bypass grafts. Aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of >75% were explanted from 14 patients at redo coronary artery bypass grafting. The grafts demonstrated two distinct forms of graft occlusion: four out of the 14 graft occlusions (29%) resulted from severe hyperplastic transformation of the intima complicated by thrombi attached to the degenerating liminal endothelium; the remaining graft occlusions (71%) were due to the development of atherosclerotic lesions associated with mural thrombosis. Hiperplastically altered intimal segments were practically free of neovascularisation while atherosclerotic-like lesions contained neovessels irregularly distributed throughout. Intimal neovessels were located exclusively in microzones enriched with VEGF-expressing cells and, furthermore, neovascular endothelial cells themselves also displayed VEGF immunopositivity. Double-immunostaining revealed that in areas of neovascularisation, the vast majority macrophages (CD68+) expressed VEGF. Some CD68+ foam cells that surrounded branches of neovascularisation were also VEGF-positive. These findings suggest that VEGF expressed by neovascular endothelial cells and by macrophages may act as a local regulator of endothelial cells functions and may induce intimal neovascularisation in aortocoronary saphenous vein bypass grafts affected by atherosclerosis.

Aged↗
PubMed2001

Incidence of acquired immune deficiency syndrome (AIDS)-related disorders at laparotomy in patients with AIDS.

BACKGROUND: Patients with acquired immune deficiency syndrome (AIDS) present for surgical management of abdominal conditions that are complications of advanced human immunodeficiency virus (HIV) infection or that are caused by other disease not related to AIDS. This study compared the clinical details and postoperative outcomes of patients with AIDS-related diseases found at laparotomy with those of patients with non-AIDS-related disorders. METHODS: The medical records of 30 consecutive patients with AIDS who underwent laparotomy were examined retrospectively. RESULTS: Fourteen patients had AIDS-related pathologies found at laparotomy, 13 had disease processes that were not AIDS related and three had no abnormal findings at laparotomy. Patients with AIDS-related conditions at laparotomy had lower mean body-weight, serum albumin concentration and CD4 lymphocyte count, and required a longer hospital admission than those who had non-AIDS-related disease. The duration of HIV infection and the number of complications and deaths were similar in the two groups. Complications occurred in 21 patients and there were five deaths (30-day mortality rate 17 per cent). CONCLUSION: AIDS-related pathologies are commonly found at laparotomy in patients with HIV/AIDS. An AIDS-related diagnosis does not confer a greater risk of complication or postoperative death than other conditions.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Documented prevalence of HIV and hepatitis C infection in patients with penetrating trauma.

BACKGROUND: Trauma patients infected with human immunodeficiency virus (HIV) or hepatitis C (HCV) pose specific problems to health-care workers due to the risk of exposure to these agents in blood and other body fluids. Studies of patients with penetrating trauma in the USA have shown a higher prevalence of HIV and HCV infection than the general population. No studies have examined the prevalence of these infections in Australian trauma patients. METHODS: The medical records of all patients presenting to St Vincent's Hospital, Sydney, from January 1994 to December 1998, with a stab wound to the neck, chest or abdomen, or with a gunshot wound to any anatomical site, were retrospectively reviewed. The number of patients with a history of HIV or HCV infection, or with risk factors for these such as male-to-male sexual intercourse and intravenous drug use, were recorded. RESULTS: The medical records of 148 patients with stab wounds to the neck, chest or abdomen, or with gunshot wounds were examined. Risk factors for HIV or HCV infection were recorded in 31 patients (21%). Two patients (1.3%) had a history of HIV infection and a further eight patients (5.4%) were known to have HCV. CONCLUSIONS: There was a high prevalence of risk factors for HIV and HCV in patients with major penetrating wounds at St Vincent's Hospital. The prevalence of documented HIV and HCV infection was subsequently greater than that expected in the general population, highlighting the risks to health-care workers managing these patients.

Adult↗
PubMed2001

Evidence that dendritic cells infiltrate atherosclerotic lesions in apolipoprotein E-deficient mice.

Earlier we reported that atherosclerotic lesions of apoE-deficient mice contained cells which stained positively with anti-S-100 antibody and that cells exhibiting the ultrastructural features of dendritic cells were present in the aortic lesions. These observations suggested that dendritic cells might be involved in mouse atherosclerosis. By employing DEC-205 and MIDC-8 antibodies specific for dendritic cells, the present study has established that dendritic cells indeed accumulate in atherosclerotic lesions of apoE-deficient mice. Finding dendritic cells infiltrating atherosclerotic lesions in apoE-deficient mice offers the possibility of investigating the migratory routes of dendritic cells and their involvement in T-cell activation.

Animals↗
PubMed2000

Identification of dendritic cells in ePTFE grafts explanted from humans.

Following implantation different cell types interact with synthetic vascular prostheses resulting in a complex immuno-inflammatory response. Dendritic cells are responsible for activating the primary T-lymphocyte immune response in various pathological conditions by their role as antigen-presenters. This study aimed at examining whether dendritic cells accumulate within small diameter expanded polytetrafluoroethylene (ePTFE, Goretex(R)) grafts explanted from humans. Segments of expanded polytetrafluoroethylene were explanted from 11 patients (6 male, 5 female), aged between 60 and 83 years (mean 70.7 years) at secondary or revision bypass operation. The graft implant duration varied from 4 months to 12 years (mean 40.5 months). Dendritic cells were identified immunohistochemically using S-100 antibody, as well as by electron microscopy. Immunohistochemical examination showed that all 11 explanted synthetic grafts contained S-100(+) cells colonising both the synthetic matrix itself, and the adjacent perigraft tissue. Electron microscopic analysis confirmed the presence of cells with a characteristic dendritic cell morphology within the grafts. Dendritic cells which accumulated within synthetic grafts were found to co-localise with T-lymphocytes. Based on these observations, we speculate that dendritic cells may be involved in the immuno-inflammatory responses following the implantation of synthetic vascular prostheses through their interaction with T-lymphocytes.

Aged↗
PubMed2000

Immunophenotypic analysis of the aortic wall in Takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions.

The present study was undertaken to examine the cellular composition of the aortic wall in Takayasu's arteritis and to investigate the association of different cell types in the immuno-inflammatory reactions of this disease. Specimens of aortic wall affected by Takayasu's arteritis were obtained from 10 patients (five male, five female), aged 32 to 68 years (mean 49.5 years) at elective operation. The mean duration of disease was 6.5 years (range 2 months to 13 years). Specimens were embedded in paraffin and the sections stained with antibodies to CD3 (to identify T cells), CD20 (B cells), S-100 (dendritic cells), CD15 (granulocytes), CD68 (macrophages), alpha-SMA (smooth muscle cells) and von Willebrand factor (endothelial cells). Immunohistochemical examination demonstrated that all specimens showed histological alteration with the replacement of the muscular and elastic layers of the media and adventitia by dense fibrous tissue, and were characterized by varying degrees of inflammatory cell infiltration. In five cases, inflammatory nodules consisting of numerous T cells and B cells were observed in the adventitia. Within the inflammatory nodules, as well as around areas of neovascularization in the deep portion of the intima, lymphocytes were co-localized with dendritic cells. In addition, in the adventitia, the accumulation of a large number of granulocytes was observed. The present study demonstrates that immune inflammation is a typical feature of Takayasu's disease, and that the interactions between dendritic cells and lymphocytes may be important in the control of the immune reactions in this vascular pathology.

Adult↗