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Biomedical subjects

B A Warren

Publications and source records attributed to B A Warren.

13 recordsLinked to original sources

The microcirculation in two transplantable melanomas of the hamster. I. In vivo observations in transparent chambers.

Twenty-eight transparent chambers were inserted into the cheek pouches of hamsters and daily serial observations made of the changing vasculature of transplants of 2 varieties (A-Mel-4B32, ZGYP1) of amelanotic melanomas. The tumor A-Mel-4B32 grew at a rate which covered 50% of the viewing area in 3--4 days, while the tumor ZGYP1 covered less than 10% of the viewing area at this time and did not cover 50% of the viewing area until 9.5 days after transplantation. The difference in growth rate was not reflected in any differences in the morphology of the vascular network and distribution of the venous arcades.

Animals

The microcirculation in two transplantable melanomas of the hamster. II. Scanning electron microscopy.

Normal and tumor vessels observed in vivo on the hamster cheek pouch membrane in transparent chambers were examined by scanning electron microscopy. Large, thin walled veins were found in the reactive zone around the 2 amelanotic melanomas of the hamster. Sinusoidal vessels and channels contained red cells, which did not possess any vascular wall, were seen in the main substance of the tumors. In this system all the vessels within the central mass of the tumor transplant comprise newly formed vessels. The surfaces of the tumor cells and the lining of the tumor vessels were examined by this technique. The biological history i.e., age of the vessel and location from the growing edge of the tumor, were known. The surface of the tumor cells on cut section differed in appearance from the areolar tissue of the pouch membrane. Scanning electron microscopy of the inner aspect of newly formed tumor vessels permits much greater sampling of the tissue than transmission electron microscopy and further work should reveal aspects of the interaction of the blood with tumor stroma.

Animals

Metastasis via the blood stream: the method of intravasation of tumor cells in a transplantable melanoma of the hamster.

Tumor cells entered the vascular compartment of transplantable amelanotic melanoma of the hasmster 3 days after transplantation, closely following vascularization of the transplant. Examination of the tortuous giant capillaries at the edge of the transplant showed tumor cells breaching the thin endothelium of these vessels. Extravasation of red cells into the surrounding tumor tissue and attempted haemostasis by small platelet aggregates attached to the vessel walls were also found.

Animals

Comparison of antithrombotic activity of heparin, ASA, sulfinpyrazone and VK 744 in a rat model of arterial thrombosis.

Rat carotid arteries were injured electrically (350 V, 2 mA DC for 5 min) before and after the intravenous administration of heparin (1,000 U/kg), VK 744 (25, 50, 100 mg/kg) ASA (100, 200 mg/kg) and sulfinpyrazone (50, 100, 150, 200 mg/kg). Thrombus growth was quantified by recording arterial temperature change distal to the injury. Heparin completely blocked thrombus formation in most experiments. All other agents exhibited antithrombotic activity with sulfinpyrazone being most potent. None was as effective as heparin. This model may be a useful tool for screening antithrombotic drugs.

Animals

Some aspects of blood borne tumour emboli associated with thrombosis.

The ultrastructural morphology of the tumour cycle which has as one of its features the blood-borne tumour embolus associated with thrombosis is illustrated by examples of four phases. (1) The intrinsic vasculature of tumours influences the process of intravasation of tumour cells to form bloodborne emboli. Scanning electron microscopy of melanoma tumours reveals channels containing erythrocytes which are sinusoidal in appearance. (2) The reaction of the circulating blood to the villi and folds of tumour cells is to coat the surface with plasma proteins and platelets. Walker 256 carcinoma cells become encrusted with platelets following agitation with rat platelet rich plasma. (3) Damaged endothelium appears to provide a more secure adhesional site for the tumour embolus. Platelets on a damaged site may provide an active adhesional region for the platelets on the passing embolus. (4) Tumour cells migrate through the endothelial layer from the adherent embolus and can be held up at the level of the basement membrane of the endothelium.

Animals

Vascularization induced in the cheek pouch of the Syrian hamster by tumor and nontumor substances.

We tested fresh amelanotic and dry amelanotic melanoma tissue, gelatin, embryo and adult connective tissue, fresh and dry liver, fibrinogen, fibrin, pouch membrane, starch, dry hamster embryo and placental tissue, and glycogen in the transparent cheek pouch chamber of the Syrian hamster to explore the specificity of tumor angiogenesis and the mechanism that may selectively inhibit proliferation of blood vessels in the pouch membrane. Differences between the proliferations induced by tumor and normal tissues, various proteins, and polysaccharides were qualitative as well as quantitative. The glucocorticoid 6 alpha-methylprednisolone (MPS) decreased and sometimes totally inhibited the vascularization phenomenon. Dry tumor tissue induced capillary proliferation in seven of eight chambers 3 days after surgery; two of seven chambers of MPS-treated animals showed a reaction 10 days after the operation. MPS suppressed (in some cases only partially) capillary proliferation in chambers with implants of adult connective tissue, fresh liver, starch, or glycogen.

Animals

The effects and morphology of atheroembolism in limb arteries: an experimental study.

Eroded atheromatous plaques which have released atheromatous material into the circulation are commonly found at autopsy in the abdominal aorta and common iliac arteries in man. In an attempt to study this phenomenon quantitatively, human atheromatous material in suspension was injected intothe femoral and common iliac arteries in rabbits. The weight of atheromatous material injected was varied. There was a critical load for the common iliac artery beyond which there was progressive ascending thrombosis and death of the animal. In rabbits weighing 3 to 5 kg, up to 0.2 g of atheromatous material could be injected intra-arterially with survival of the animal and without producing observable effects. As the amount was increased there was a narrow zone in which survival of the animal with a limp occurred. Beyond 0.2 g, death resulted from ascending thrombosis of the peripheral limb arteries. This eventually reached the bifurcation of the oarta and obstructed the opposite common iliac artery. A thrombus rapidly formed around the atheromatous material. Examination of the atherothrombus by light, transmission electron and scanning electron microscopy showed that it contained cholesterol crystals, lipid material, many platelets, leucocytes and red cells bound together within a fibrin net. The atheromatous material was for the most part in the core of the thrombus.

Animals

The ultrastructure of the reaction of arterial walls to cholesterol crystals in atheroembolism.

Scanning electron microscopy of atheromatous material revealed flat rhombic cholesterol crystals piled one upon the other. The fate of cholesterol crystals in the atheromatous material was followed after injection intra-arterially into the left renal arteries and left common carotid arteries of rabbits. The lipid and membranous component of the atheromatous material disappeared from the lumen of the vessels in 2-3 days after injection. Macrophages engulfed small cholesterol crystals and exposed surfaces attracted a layer of platelets. Larger cholesterol crystals evoked a giant cell response while within the lumen. Some cholesterol crystals penetrated the vessel walls or were included in the vessel wall reaction and induced a covering of endothelial cells sequestrating them from the lumen. The cholesterol crystals contained in some of the macrophages showed fracture lines and in some instances there were associated myelin figures. Large cholesterol crystals eventually elicited a fibroblastic response from the vessel wall (at about 1-4 weeks after injection) which could give rise to partial or almost complete occlusion of the vessel lumen.

Animals

The scanning electron microscopy of the lysis of fibrin by endothelium.

The lysis of a fibrin clot by sheets of endothelium one cell thick was examined by scanning electron microscopy. The unlysed fibrin film appeared as a densely matted surface, without interstices. Commencing lysis appeared as parallel ovals in which the dense matting was altered to show many strands of fibrin criss-crossing the lytic "window" with many interstices. The wall of the lytic crater surrounding the sheets of endothelium revealed a network of fibrin strands. There was condensation of the fibrin at the edge of the hole at the external surface. The floor of the crater contained sheets of endothelium which were recognized by the shape and size of the nuclei. Flocculent masses of precipitate were present on the endothelial cells in the floor of the crater and occasionally within the lysed ovals at the edge. These may be fibrin degradation products.

Animals

Electron microscopy of the sequence of events in the atheroembolic occlusion of cerebral arteries in an animal model.

Atheromatous material was removed from human atheromas, suspended in sterile saline in the ratio of 1 g to 5 ml and ground to allow passage through a needle; 0-5 ml of this suspension was injected into the left common carotid artery of 16 rabbits. Six animals died after the injection. The remaining animals were killed after various time intervals and the occluded arteries studied by electron microscopy. The general pattern of the embolic event in the cerebral arteries was that there were 3 groups of changes. Firstly, an immediate period of atherothrombotic occlusion occurred, which was followed by some resolution of the obstruction so as to leave the cholesterol crystals of the embolus stuck in the vessel walls as the only remaining element of the embolus in some cases. Finally, there was a late period in which the cholesterol crystals were isolated from the lumen of the vessel and surrounded by macrophages, fibroblastic cells and collagen. Endothelial lined channels developed in the original obstruction.

Animals

Filtration of cryoprecipitate: a microscopic assessment of filter depostion.

A recent survey indicated that many Canadian hemophiliacs and physicians did not consider it necessary to filter cryoprecipitate prior to infusion. Experiments were performed to demonstrate that no loss of factor activity resulted from filtration of cryoprecipitate through standard blood filters. Furthermore, examination of the material retained on standard and ultrafiltration elements using scanning and transmission electron microscopy demonstrated the presence of amorphous and fibrillar proteins that proved to be largely composed of fibrin. This was accompanied by cellular material including intact and disintegrating leukocytes, erythrocytes, and platelets. Nonbiologic material was also discovered, including cellulose and plastic debris. This study emphasizes the need for effective filtration of cryoprecipitate.

Chemical Precipitation