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Biomedical subjects

G I Schoefl

Publications and source records attributed to G I Schoefl.

At least 19 recordsLinked to original sources

Coronary C-reactive protein distribution: its relation to development of atherosclerosis.

Two hundred and ninety-nine paraffin-embedded human coronary artery sections from 68 autopsies, both male and female and with various causes of death, were examined for distribution of C-reactive protein (CRP) using the indirect immunofluorescence technique and high-resolution confocal microscopy. The results demonstrate, for the first time, the existence of CRP in human coronary arteries, with evidence of CRP deposits being associated with lipids within in the artery walls. Grades of CRP immunoreactivity positively correlate with relative intimal thickness and negatively correlate with relative lumen size. It is suggested, therefore, that CRP may be related to the development of atherosclerosis and that the development of coronary atherosclerosis is associated with a relapsing inflammatory/necrotic process occurring within the coronary intima.

Adult↗

Immunohistochemical study of intimal microvessels in coronary atherosclerosis.

Two hundred ninety-nine human coronary artery paraffin-embedded tissue blocks were examined for intimal microvessel invasion by probing for factor VIII-associated antigen with indirect immunofluorescence and high resolution confocal microscopy. The results obtained confirm that intimal microvessels originate in the adventitia and show that the richness of intimal microvessels is strongly positively correlated with intimal thickness and negatively correlated with relative lumen size. A number of plasma constituents were examined in serial sections. Comparison of immunofluorescence distribution patterns of these components with intimal microvessel distribution patterns reveals that intimal microvessels leak plasma albumin into artery walls, exude fibrinogen, and are associated with the build-up of plasma cells within atherosclerotic lesions. Therefore, intimal microvessels are demonstrated to play important roles in the development of atherosclerosis.

Antibodies↗

Plasma protein insudation as an index of early coronary atherogenesis.

Two hundred ninety-nine paraffin-embedded coronary artery blocks from 68 autopsy cases were serially sectioned. The blocks were selected to provide a range from normal through various stages of atherosclerosis, and sections were examined with the indirect immunofluorescence technique for intramural distribution of plasma albumin, fibrinogen, and immunoglobulin gamma (IgG). Cryostat-sections of 44 blocks from 22 of the same cases were examined with the same technique for distribution of apolipoprotein B. Alteration of protein insudation in the artery wall was a sensitive index of coronary atherogenesis. The sequence in which these proteins were involved in the initiation and development of early atherosclerotic lesions was analyzed by determining the average relative intimal thickness and relative lumen size that was associated with the first occurrence of altered insudation of each of these proteins. Results indicate that changed plasma albumin insudation is the earliest sign of a focal intimal lesion, and increasing albumin insudation shows the strongest association with intimal plaque growth. The other proteins tested showed altered insudation, in the order IgG, fibrinogen, apolipoprotein B. The results indicate that a progressive increase in permeability of the coronary artery endothelium occurs in the early stages of atherogenesis. Patterns of IgG localization provide evidence of both early systemic and subsequent local immune reactions being involved in atherogenesis. Altered albumin and apolipoprotein B insudation levels have stronger correlation coefficients with relative intimal thickness and relative lumen size than do those IgG and fibrinogen. The extremely high correlation coefficients shown by albumin emphasizes the importance of edema in determining plaque size and lumen stenosis.

Adult↗

A method for embedding thin membranes in historesin.

A method is described for flat-embedding thin membranous tissues in Historesin. It allows easy orientation for sectioning large areas parallel to the surface. Selected fields can be monitored from the unfixed specimen, throughout preparation, to mounting on the microscope slide. For cross-sectioning, the flat-embedded tissue can be stacked and re-embedded to increase the amount of material examined per section.

Animals↗

Microvasculature of normal and involuted mouse thymus. Light- and electron-microscopic study.

The spatial arrangement of blood vessels in the thymus of normal and hydrocortisone-injected mice was studied by light and electron microscopy. The thymus is supplied by one thymic artery which branches into arterioles as it enters the parenchyma. These, in turn, feed capillary networks in the cortex and in the medulla. Cortical networks at the periphery of the lobule form loops which return blood to postcapillary venules at the corticomedullary junction and in the medulla. There is no subcapsular venous drainage. The overall distribution of blood vessels in the involuted thymus is essentially the same as in the normal thymus but the pattern becomes irregular and the vessels are tortuous. The endothelium of the postcapillary venules is flat and surrounded by a wide perivascular space containing many lymphocytes. This space is delimited by basal laminae, on the one side by that of the abluminal surface of the venular endothelium, on the other side by that of a thin, sheet-like epithelial layer formed by cytoplasmic processes of reticular cells. The perivascular space is in continuity with the surrounding interstitial space via gaps in its epithelial sheet. It does not form continuous longitudinal channels along the venules, but is interrupted by epithelial trabeculae. There is no obvious difference in structure between the postcapillary venules and their perivascular space of normal and those of involuted thymuses. Lymphocytes are intercalated in the venular endothelium particularly in involuted glands. They are present in the perivascular space and in gaps of the outer epithelial sheet. These findings suggest that the postcapillary venules and the perivascular spaces may function as pathways for the migration of thymic lymphocytes into or out of the blood circulation.

Animals↗

The vasculature of the guinea-pig thymus: topographic studies by light and electron microscopy.

The three-dimensional vascular distribution and the vascular-parenchymal relationship in normal guinea pig thymus were studied by light, scanning and transmission electron microscopy. Interlobular arteries arising from one thymic artery entered the thymic parenchyma where they branched into arterioles and then formed capillary networks in the cortex and in the medulla. Most cortical capillaries drained to the surface via perpendicular venules which merged into the subcapsular veins. Some vessels of the inner cortex, however, returned blood to the postcapillary venules (PCVs) at the cortico-medullary junction and in the medulla. The vascular supply of the guinea pig thymus is thus characterized by a dual circulation in which venous blood drains either via a subcapsular or via a cortico-medullary route. The endothelium of the postcapillary venule (PCV) was flat and often contained migrating lymphocytes. These venules were surrounded by a perivascular space (PVS) which separated the vessel from the parenchyma and which contained many lymphocytes. This PVS was not lined by cells but was delimited on one side by the abluminal surface of the venular endothelium and on the other side by a thin, sheet-like layer formed by cytoplasmic processes of epithelial reticular cells. This epithelial sheet was not continuous, as there were frequent interruptions or gaps where the PVS communicated directly with the intercellular mesh of the thymic parenchyma. The PVS did not form a continuous longitudinal channel but was interrupted by epithelial trabeculae. Some macrophages and a few plasma cells were seen in the parenchyma near the PVS. These findings suggest that the PCV and the PVS in the thymus may function as pathways for the migration of lymphocytes into or out of the blood circulation.

Animals↗

The popliteal lymph node of the mouse: internal architecture, vascular distribution and lymphatic supply.

The architecture of the mouse popliteal lymph nodes differs from that shown in conventional diagrams. The cortical lymphoid tissue, rather than forming a continuous outer layer, is organised into one or two hemispherical aggregates which project towards the hilus. These aggregates are surrounded by medullary tissue which thus extends to large areas of the surface of the node. The vascular distribution in the lymphoid aggregates is relatively sparse and contrasts with the dense meshwork of capillaries and venules around them. It also contrasts with the high vascularity of medullary tissue. Arterial vessels, especially those of larger calibre, are predominantly seen in the hilar area of the node suggesting that there is extensive branching as the artery enters the node. Capillaries associated with the lymphoid aggregates are usually lined by continuous endothelium, while those in the medulla are generally of the fenestrated type. The microcirculation has an extensive venous capacity and many venous segments are high endothelium venules whose walls are permeated by lymphocytes. Each node receives one or two afferent lymphatic vessels and is drained by up to four or five efferent lymphatic vessels. In approximately half the nodes examined, there were extranodal communications between afferent and efferent lymphatic vessels allowing some lymph to bypass the node.

Animals↗

Topographical studies of lymphocyte localization using an intracellular fluorochrome.

A procedure for analysing the topographical localization in tissue sections or whole-organ mounts of lymphocytes labelled with an intracellular DNA-binding fluorochrome, Hoechst dye No. 33342, is described. The localization of intravenously injected lymphocytes in spleen, popliteal lymph nodes, and Peyer's patches was followed up to 7 days. In the case of spleen, both B and T lymphocytes initially localised in the marginal zone. Subsequently, B cells appeared to exit via the red pulp, while T cells aggregated around vessels in the white pulp. In Peyer's patches, B and T lymphocytes localized to different lymphoid areas. The advantages and potential applications of this technique are discussed.

Animals↗

Pathological vascularization of the coronary intima.

Secondary vascularization was found in the walls of diseased coronary arteries from 36 individuals who died after sudden cardiac arrest. In the series presented here, coronary arteries of hospital patients dying from all causes also showed a 100% incidence of pathological neovascularization. A process linking neovascularization and chronic inflammation to an ultimate infectious aetiology is suggested.

Adult↗

Blood vessels of the Peyer's patch in the mouse: I. Topographic studies.

The topographic distribution of blood vessels in Peyer's patches of mice was studied by light and scanning electron microscopy with whole mounts of flattened gut segments and vascular corrosion casts. Peyer's patches are imbedded in the intestinal wall and share its blood supply. Two to four mural trunks may contribute to the area of the patch. In and around the lymphoid nodules the microcirculation is highly specialized. The nodule is permeated by a meshwork of fine capillaries that is supplied by arterioles entering on the serosal and lateral surfaces. Blood flow to the lymphoid nodule appears to be monitored by arterial sphincters; the dense lymphatic tissue can also be bypassed by arteriovenous communications. An extensive venous network encircles the nodule. Most of these venules are lined by high endothelium which is penetrated by lymphocytes. The geometry of these vessels suggests a slow and turbulent flow in these vascular segments that may aid margination of lymphocytes. A planar capillary plexus lies subjacent to the mucosal epithelium in the dome area.

Animals↗

Blood vessels of the Peyer's patch in the mouse: II. In vivo observations.

A technique was developed that allowed the in vivo observation of Peyer's patches in the mouse for several hours. Untreated animals and animals depleted of lymphocytes were used. In this species, blood vessels associated with the lymphoid nodules are readily visible through the thin serosal muscle coat. High-endothelium venules are recognized by the large number of refractile cells that adhere to the luminal surface. A colloidal carbon suspension injected intravenously labeled high-endothelium venules and was only rarely seen in arterial and capillary segments or in venules of the gut parenchyma. When fluorescein isothiocyanate-labeled (FITC-labeled) syngeneic spleen cells were injected, they appeared in vessels of the Peyer's patch within a few seconds and began to adhere to the luminal surface of high-endothelium venules. In untreated animals, peak numbers of fluorescent cells were reached after about 20 min. Many adhered but some were swept away. In lymphocyte-depleted animals, however, peak numbers were reached after only a few minutes and most cells remained attached.

Animals↗

Blood vessels of the Peyer's patch in the mouse: III. High-endothelium venules.

High-endothelium venules of mouse Peyer's patches were examined by scanning electron microscopy, and a quantitative assessment was made of the location of lymphocytes in relation to endothelial cells. Untreated mice and mice with markedly depressed levels of circulating lymphocytes were used. Lymphocytes were divided into adhering and migrating cells and as to association either with the body of the endothelial cell or with its cell border. Over 90% of all adhering cells and the great majority of migrating lymphocytes were located at the cell border. The exception was one animal in which most migrating lymphocytes appeared to penetrate the endothelial cells. Our data lend strong support to the currently held view that most migrating lymphocytes traverse the endothelium by following an intercellular path but that, under certain conditions, lymphocytes may penetrate the cytoplasm of endothelial cells.

Animals↗

Hereditary thrombocytopathy: a familial bleeding disorder due to impaired platelet coagulant activity.

A family with a bleeding disorder due to congenital thrombocytopenic thrombocytopathy is described, with ten affected members in three generations. The disorder is inherited as an autosomal dominant trait and is characterized by thrombocytopenia, morphologically abnormal platelets, prolonged bleeding time, platelet coagulant activity deficiency and abnormal platelets, prolonged bleeding time, platelet coagulant activity deficiency and abnormal platelet aggregation. Patients' platelets adhered to collagen, but aggregation was reversible and the release of platelet constituents was minimal. Aggregation with ADP was similarly reversible, but the platelet response to thrombin was normal. These defects in platelet aggregation and release were not corrected by addition of normal plasma indicating an intrinsic abnormality of platelets. By definition thrombocytopathy consists of a deficiency in platelet coagulant activity. It was shown that the deficiency of platelet coagulant activity caused a delay and decrease in the conversion of prothrombin to thrombin, and it is proposed that the lack of thrombin accounts for the defective release reaction and the reversible aggregation. An adequate haemostatic plug due to decreased release of ADP, together with instability of the plug provide an explanation for the bleeding tendency in thrombocytopathy.

Adenosine Diphosphate↗

Anti-horseradish peroxidase associated with Golgi complex of antibody-forming cells.

Observations are reported on the localization of anti-horseradish peroxidase in antibody-forming cells in popliteal lymph nodes following a single injection of antigen. Reaction product, marking the site of antibody, was observed not only in the ergastoplasm and cisternae of the Golgi complex, but also in globules associated with the Golgi complex.

3,3'-Diaminobenzidine↗