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Biomedical subjects

P A McCuskey

Publications and source records attributed to P A McCuskey.

24 records · Page 2Linked to original sources

In vivo microscopy of the hepatic microvascular system.

In vivo microscopic study of the responses of the various segments of the hepatic microvascular system to adrenergic, cholinergic, and other aminergic substances and their antagonists have revealed the relative distribution of receptor sites in these various vessels. The results also suggest a possible interaction of cholinergic substances with periportal mast cells. The release of serotonin, histamine and possibly other products from these cells results in dramatic alterations in blood flow through the hepatic sinusoids due to the adhesion of leukocytes and platelets to the endothelium.

Animals↗

Intrahepatic distribution of nerves in the rat.

The intrahepatic distribution of nerves in the rat was studied using neurohistochemical and electron microscopic methods. Innervation was restricted primarily to vessels in the portal space and hilus. Both adrenergic and cholinergic fibers were observed in the adventitia of hepatic arteries, and to a lesser extent adjacent to portal veins. Some of the cholinergic fibers, however, were not contiguous with the vasculature. Near the hilus many of these fibers were associated with ganglia while peripherally some coursed into the immediately adjacent parenchyma where end bulbs abutted on hepatocytes. Ultrastructurally, scattered small nerves, devoid of neurolemma, were found contiguous with the portal lamina of hepatocytes. Nerve fibers deeper within the lobule were not seen but numerous gap junctions were observed between contiguous hepatocytes. Central and sublobular hepatic veins lacked innervation but adrenergic nerves were demonstrated in the walls of larger hepatic veins. Innervation of the biliary system was sparse. While nerves were interposed between vessels and bile ducts, such nerves tended to be associated more closely with the vasculature.

Acetylcholinesterase↗

In vivo microscopy of the spleen.

The use of improved in vivo microscopic methods has permitted a reevaluation of the "open" vs. "closed" theory of blood flow through the splenic red pulp. The microscopic methods used for studying the spleen in vivo are described as are the results, both of which were presented in motion picture form at this symposium. The results strongly suggest that, in general, there is little or no continuity of endothelium through the splenic red pulp. Instead, blood flows from "arterial" capillaries lined with endothelium into channels within the red pulp formed by the cytoplasmic processes of reticular cells. In vivo these processes appear similar to endothelium. Blood leaves the red pulp by passing through apertures in the endothelium of sinuses and venules.

Animals↗

Studies of the hemopoietic microenvironment. IV. In vivo microscopic and histochemical study of allografts of bone marrow in the hamster cheek pouch chamber.

Within a transparent chamber enclosing subcutaneous tissue of the hamster cheek pouch, allogeneic femoral marrow was grafted. This permitted in vivo microscopic study of the grafts for 14 days. Five to seven days after grafting, blood flow was established within sinusoids arranged in interconnecting polygonal networks, a pattern characteristic of marrow. All vessels appeared to have a complete and continuous endothelial lining. The graft contained foci of erythropoiesis, granulopoiesis, and megakaryocytopoiesis, but no osteogenic activity. Degeneration of the grafts began to occur between days 9 and 13 after implantation. Generally, this was preceded by infection within the chamber, fibroblastic proliferation, and an accumulation of acid mucopolysaccharide in the stroma. The concomitant loss of hemopoiesis and accumulation of acid mucopolysaccharides was consistent with our hypothesis reported previously that excessive concentrations of acid mucopolysaccharide in the hemopoietic microenvironment are not conducive to supporting hemopoiesis, especially erythropoiesis. Degeneration of the grafts probably was the result of infection since there was no evidence of an immunologic response to the graft, and in chambers not containing grafts, similar infections and changes in the connective tissue were observed. The technique of grafting marrow into the hamster cheek pouch chamber provides a model for long-term, in vivo microscopic study of bone marrow. However, methodologic improvements, especially in the control of infections, are needed.

Animals↗

Phagocytosis, an unrecognized property of murine endothelial liver cells.

Impairment of the phagocytic capacities of Kupffer cells, as is found in Frog Virus 3 hepatitis of mice, allows the endothelial liver cells to take up intravenously inoculated latex particles of 1.0 micron diameter. In vitro experiments with cultivated endothelial cells isolated by collagenase perfusion of the liver and purified by centrifugal elutriation demonstrate that uptake occurs via a typical mechanism of phagocytosis involving pseudopodia. Ingestion of latex is inhibited by incubation of the cells at 4 degrees C and by treatment with cytochalasin B, whereas colchicine has no effect. These results demonstrate that: the Kupffer cells are not the only cells of the hepatic sinusoid capable of phagocytosis; and under conditions where the phagocytosis in Kupffer cells is impaired, the endothelial cells may participate in the clearance of large particles from the blood.

Animals↗

Kupffer cell function in host defense.

High-resolution in vivo microscopic methods have been used to explore the responses to endotoxin of Kupffer cells in the livers of anesthetized mice, rats, hamsters, and guinea pigs under a variety of experimental conditions. These include studies of normal animals as well as of animals sensitized or tolerant to endotoxin, C3H/HeJ mice with a low response to endotoxin, mice rendered septic by cecal ligation and puncture, mice with Kupffer cells selectively destroyed by frog virus 3, and rats with portacaval shunts. The functional state of Kupffer cells was evaluated by measuring both the number of these cells per microscopic field that phagocytosed 1.0-micron latex particles and the rate at which individual Kupffer cells phagocytosed single latex particles. The intrahepatic density and level of activation of Kupffer cells were found to play a role in determining endotoxin sensitivity and to be involved, in conjunction with endotoxin, in the development of tolerance. All of these studies support the concept of a central role for Kupffer cells in host defense mechanisms and of the possible modulation and of this role by gut-derived endotoxins contained in the portal blood.

Animals↗