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Biomedical subjects

T Heath

Publications and source records attributed to T Heath.

At least 37 records · Page 2Linked to original sources

Lymph pathways associated with Peyer's patches in sheep.

Lymphatic drainage of the ileum associated with Peyer's patches begins with lymph entering a single lacteal of the villus, probably through intercellular flaps, which prevent retrograde flow to the interstitium. These lacteals are continuous with an interconnecting plexus of branching sinuses which surrounds the crypts and follicle domes in the lamina propria. Small vessels emanating from this plexus penetrate the muscularis mucosa, where lymph can either flow within septal vessels to the deep submucosa, or enter the follicular sinuses to move freely around follicles, and through gaps in septal walls. All lymph enters a deep submucosal network where retrograde flow is prevented by valves. Lymph is then conveyed through vessels passing between the fibres of the muscularis externa to other lymphatics, which transport lymph from the ileal surface to the mesenteric nodes.

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Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep.

We studied the effects of liposomes on the pulmonary circulation of sheep and found a close correlation between liposome retention in the lung and the intravascular macrophages. A test dose of liposomes (5.5 mumol of total lipids) injected intravenously transiently increased pulmonary arterial pressure from 24 +/- 2 to 55 +/- 16 (SD) cmH2O. The pulmonary arterial pressure responses were dose dependent and reproducible. The rise in pulmonary arterial pressure was blocked completely by indomethacin and 75% by a thromboxane synthase inhibitor. Systemic arterial thromboxane B2 concentration increased from a base-line level of less than 50 pg/ml to 250 +/- 130 pg/ml at the peak of the pressor response. Larger doses of liposomes (220 mumol of total lipids) infused intravenously over 1 h increased pulmonary arterial pressure maximally within the first 15 min. Lymph flow increased and lymph protein concentration decreased, suggesting venoconstriction. Over half (62.4 +/- 15.7%) of 111In-labeled liposomes remained in the lung after 2 h. Fluorescence and transmission electron microscopy showed that greater than 90% of the liposomes were associated with mononuclear cells in the lumen of the alveolar wall microvessels. We conclude that liposomes affect pulmonary arterial pressure transiently by a mechanism involving the arachidonate cascade, principally thromboxane. Our observations suggest that a population of pulmonary intravascular macrophages is likely to be the source of the thromboxane and the pulmonary hemodynamic and lymph dynamic changes that occur in a dose-dependent fashion, although interactions between liposomes, leukocytes, or endothelial cells, in addition to the macrophages, have not been completely ruled out. We believe this is the first demonstration that pulmonary intravascular macrophages may be the source of the arachidonate metabolites rather than endothelial cells, neutrophils, or perivascular interstitial cells.

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Pathways of lymph flow through superficial inguinal lymph nodes in the pig.

The pig lymph node has an unusual structure in that tissue containing lymph nodules generally occupies a central position. Our aim was to describe the lymphatic pathways through this node. We studied the structure of these pathways with light and electron microscopy, made casts of lymphatic vessels and sinuses with Microfil, and studied the distribution within the node of subcutaneously injected carbon particles. Most afferent lymphatics penetrate deeply within the node, where they give off several branches to peritrabecular sinuses that ramify through centrally located nodular tissue. However, where an afferent lymphatic enters the node there is a subcapsular sinus over an area of nodular tissue that occupies a conventional superficial position. Some lymph reaches this sinus from the central peritrabecular sinuses, but there can also be direct communications between this sinus and the afferent lymphatic. After flowing through sinuses in nodular tissue, lymph enters tissue that is analogous to medullary tissue in other species. This tissue is of two types, one consisting mainly of a diffuse network of reticular cells around spaces up to 10-12 microns across, and one that more closely resembles conventional medullary tissue. Lymph then flows to collecting ducts, which lack valves, and then to efferent lymphatics. Our findings do not support suggestions that a purely physical obstruction of lymphocytes in the lymph node accounts for the dearth of lymphocytes in efferent lymph of pigs.

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Arterial supply to the pig intestine: an unusual pattern in the mesentery.

The arrangement of arteries in the mesentery in pigs was studied with latex casts and light microscopy. Arterial arcades, which are characteristic of the mesentery in man and other species, are absent. Instead, a narrow band of numerous, anastomosing arteries gives rise to up to about 500 bundles of arteries and accompanying veins, which radiate out in the mesentery. Each bundle contains up to 30 arteries, but these recombine as they approach the jejunum, and form 1-4 arteriae rectae. The significance of the very large number of small arteries in the mesentery is not known, but they may play a role in the control of blood pressure in the intestinal wall, or as sites of countercurrent exchange.

Animals↗

New methodology for liposome targeting to specific cells.

The specificity of liposomes for different cell types was achieved by conjugation to monoclonal antibodies directed against various cell surface antigens. L929 mouse fibroblast cells were targeted with liposomes conjugated to anti-H2Kk. K562 cells, a human line derived from chronic myelogenous leukemia, were targeted with antiglycophorin. One murine T-lymphoma, AKR/J SL2, was targeted with anti-thy 1.1; another, R1.1, was targeted with anti-H2Kk. The following important parameters were established concerning efficacy of antibody-directed liposomes as a drug delivery system. (1) Targeted liposomes containing methotrexate-gamma-aspartate were 20-40 times more cytotoxic than the free drug or nonspecific liposomes. (2) The use of drugs such as methotrexate-gamma-aspartate, which are unable to enter cells without a carrier, eliminates the nonspecific effects of drug that may leak from the liposomes. (3) Liposomes conjugated to antibody have a higher valency than the soluble antibody and bind to cells with up to 1000-fold higher affinity constant. (4) Liposomes that interact with more than one type of ligand on the cell surface show marked resistance to inhibition of cell association by soluble ligands. (5) The optimal liposome size appears to vary from 0.05 to 0.1 mu, depending on target cell type.

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The arterial supply to lymph nodes in sheep.

The aim of this study was to describe how lymph nodes in sheep receive their blood supply, and to provide some information on the pathways followed by arteries and their branches within the nodes. It was found that considerable variation exists in the arterial supply to lymph nodes in sheep. Each node may receive branches from one, two or three major arteries; the nodes may be up to 10-15 cm from these arteries, but some arteries actually pass through lymph nodes. Most branches enter at a hilus, which varies in shape, size and location, but some penetrate the capsule directly. Within the node, arteries may either proceed directly towards the cortex or extend longitudinally through the medulla; in each case branches are given off to supply the medulla and, in greater numbers, the cortex. Some arteries then leave the node through the capsule and either supply perinodal fat and/or more distal structures, or join other arteries. Anastomoses may also occur before the arteries enter a node, or within the node or at its surface. These direct anastomoses and arterial circles could play a part in maintaining the blood supply to a node when it is being bombarded with microorganisms and inflammatory products from an area of infection.

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Lymphatic and blood vessels of the popliteal node in sheep.

Our aim was to describe the lymphatic and blood vascular pathways to and from the popliteal lymph node in sheep. The blood vessels and lymphatics were filled with Microfil, and were cleared in methyl salicylate. Afferent lymphatics divide and anastomose as they pass dorsally along the lateral saphenous vein, and 6-12 lymphatics reach the node. Each branches extensively on the surface of the node giving rise to 20-50 terminal afferents which enter the node over a roughly circular area. Most enter the subcapsular sinus, but some penetrate deeply into the node. Lymph leaves the node through numerous initial efferent lymphatics, many of which contain valves. These join forming progressively larger vessels, and 2-4 efferent trunks emerge from the hilus. The hilus varies considerably in shape, depth and location, and it is filled with fat. Either a single artery, or up to 10-12 arteries derived from an anastomotic network or circle, enter the node from the hilar fat pad. Arteries may also enter at other sites. The arteries originate from the caudal femoral, or the medial circumflex femoral artery; a single node may receive blood from both arteries. This arrangement may help to maintain blood flow especially during an immune response, and despite external pressures applied to the arteries and node during movements of the animal.

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Angles of branching and the diameters of pulmonary arteries in relation to the distribution of pulmonary lesions in canine dirofilariasis.

Latex casts were made of the pulmonary arteries in 10 normal dogs. These casts were used to measure the angles of deviation of the right and left pulmonary arteries from the pulmonary trunk. The measurements were made in three projections. In both craniocaudal and dorsoventral projections the right pulmonary artery deviated more from the axis of the pulmonary trunk than did the left pulmonary artery. In the lateral projection, the right artery deviated ventrally and the left deviated dorsally, but the angles of deviation were similar. The diameter of the right pulmonary artery was significantly larger than that of the left. This difference in size of the major arteries could be a major determinant in the distribution of lesions in dirofilariasis. However the curved pathway taken by the blood as it is ejected from the right ventricle and the angles of deviation of the arteries as they branch from the pulmonary trunk could also play a part in the distribution of the lesions.

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Preparation of unilamellar liposomes of intermediate size (0.1-0.2 mumol) by a combination of reverse phase evaporation and extrusion through polycarbonate membranes.

Liposomes can be prepared by a combination of reverse phase evaporation and sequential extrusion through polycarbonate membranes. The vesicles have diameters in the range 0.05-0.5 micron and are mostly unilamellar as indicated by electon microscopy, capture volume, and availability of reactive groups to periodate oxidation. Sequential extrusion leads to a decrease in the encapsulation efficiency by 2-4-fold, depending upon the lipid composition. The inclusion of cholesterol at a 1 : 1 molar ratio of cholesterol-to-phospholipid increases both the mean size and the size heterogeneity of the liposomes as measured by negative-stain electron microscopy. The mean size of vesicles with an equal molar ratio of cholesterol-to-phospholipid after extrusion through a 0.1 micron membrane is 0.140 micron. Vesicles composed of phosphatidylglycerol/phosphatidylcholine (1 : 4) have a mean size of 0.08 micron after extrusion through a 0.1 micron membrane. The intermediate-size (0.1-0.2 micron) vesicles formed by this process have an aqueous space-to-lipid ratio of 3 : 5 and capture between 12 and 25% of the aqueous phase. The procedure is relatively simple, rapid, and yields almost quantitative recovery of vesicles that encapsulate a large percentage of the total aqueous space.

Carbonates↗

Defining aims for a veterinary school.

The Faculty of Veterinary Science at the University of Queensland has defined the aims of the Veterinary School for the future. The aims are to foster excellence in teaching, research, and other forms of professional activity in veterinary science. These aims are being used as a basis for future planning within the School.

Attitude to Health↗

Effect of electrical stimulation of the vagus nerves on bile secretion in Anaesthetized sheep.

Bile was collected before and during electrical stimulation of the vagus nerves in acute experiments on sheep with ligated cystic ducts. Most stimuli caused no change in bile formation, but a 10-V, 10-Hz stimulus caused a slight increase in bicarbonate output. Neither the response to infused secretin nor the maximum rate of bile salt transport by liver cells changed during vagal stimulation. It was concluded that the vagal innervation of the liver is not likely to play a major role in the regulation of bile formation in sheep.

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