Biomedical subjects
N D Anderson
Publications and source records attributed to N D Anderson.
Skeletal changes during prolonged external irradiation: alterations in marrow, growth plate and osteoclast populations.
This report describes hematologic and skeletal changes in young mice subjected to continuous external whole body irradiation (45 rads/day) for 4 days to 12 weeks. Irradiation caused a rapid depletion of hematopoietic stem cells, marrow aplasia and pancytopenia, all of which persisted during the period of irradiation but resolved afterward. In spite of suppressed cellular proliferation and disarray of cartilage cell columns in metaphyseal plates, linear bone growth appeared to continue at physiologic rates. Histologic and morphometric studies provided no evidence of impaired osteoblast function, but the presence of thickended trabeculae beneath the growth plate and of cartilagenous islands within cortical shafts of long bones indicated that bone remodeling was deficient. Direct osteoclast counts demonstrated that marrow aplasia was followed by a progressive decline that could not be reversed by parathormone injections or infusions with mature macrophages and lymphocytes but that resolved once the bone marrow recovered following cessation of irradiation. Therefore, the altered bone remodeling probably resulted from radiation injury to osteoclast precursors in the hematopoietic compartment.
The politics of age exclusion: the Adults Only Movement in Arizona.
Explore the source record for details and available documents.
Pathogenesis of vascular injury in rejecting rat renal allografts.
Unmodified rejection of rat renal allografts was characterized by the early onset and rapid progression of endothelial damage in venules and capillaries which culminated in ischemic cortical necrosis. This pattern of endothelial injury correlated with lymphocyte accumulation in vascular lumens and could not be duplicated by renal perfusion with alloantibodies or prevented by C'3 depletion. In contrast, endothelial integrity and normal graft function were maintained over study intervals extending to 200 days when Brown Norway (BN) rat kidneys were transplanted into Lewis (Le) rat kidney recipients subjected to neonatal thymectomy or lymph drainage. Vascular lesions occurred when syngeneic thoracic duct lymphocytes were transfused into these recipients, but irreversible endothelial injury could be prevented by simultaneous injections of immune plasma. These findings indicate that the destruction of donor endothelium is mediated by thymus-dependent immune mechanisms which can be altered by thoracic duct drainage to promote indefinite survival of renal allografts across major histocompatibility loci.
Heparin-induced coagulopathy.
Intravenous heparin, at doses of 3.0 U./gm of body weight, produced an intravascular coagulopathy in rats which was manifested by intestinal tract hemorrhage, a reduction in plasma fibrinogen concentration, a rise in fibrinogen-fibrin degradation products, and the absence of a rise in platelet count noted in the control animals. This coagulopathy could not be produced by conventional anticoagulant doses of heparin or the injection of large doses of heparin in the presence of protamine sulfate. Specific studies excluded hypoxemia, metabolic acidosis, and endotoxemia as possible etiologic factors. The coagulation abnormalities observed in this study differ from those produced by injection of other polyanionic substances but their precise pathogenesis is still uncertain.
Suppression of graft-versus-host reactions by D- and L-chloramphenicol.
Explore the source record for details and available documents.
Specialized structure and metabolic activities of high endothelial venules in rat lymphatic tissues.
Microscopic, histochemical and ultrastructural techniques were used to define characteristics of high endothelial venules (HEV) in rat lymphatic tissues. This endothelium contained acetyl esterase and acid hydrolase activities which were not altered by lymphocyte depletion. No immunoglobulins were detected on luminal surfaces of HEV by fluorescent antibody staining. Only minor structural differences were seen between HEV within lymph nodes and Peyer's patches. At both sites, high endothelial cells were linked together by macular junctional complexes and interlocking basal foot processes. Endothelial cell cytoplasm moulded about surfaces of lymphocytes migrating through the venular wall, and flocculant deposits of basement membrane formed over lymphocytes penetrating the basal lamina. The endothelium was ensheathed by three to five layers of overlapping reticular cell plates and connective tissue. Each plate was linked to the reticular meshwork of the node by collagen bundles and anchoring filaments which inserted into the plate's external limiting membrane. This permitted individual paltes to separate or approximate each other as tissue and intravascular pressure varied, and lymphocytes moved across the sheath by insinuating themselves into gaps between overlapping plates. This composite structure of the HEV wall appeared to facilitate lymphocyte entry into the node and minimized vascular leakge.
Lymphocyte emigration from high endothelial venules in rat lymph nodes.
Sequential events during lymphocyte emigration from high endothelial venuses (HEV) were studied by scanning and transmission electron microscopy combined with regional perfusion techniques. The results indicate that blood lymphocytes selectively adhere to HEV surfaces through microvilli which attach to shallow pits on the luminal surfaces of high endothelial cells. These intercellular contact points resist hydrodynamic and osmotic shearing forces, but can be disrupted by treatments which remove endothelial glycocalyx, hydrolyse lymphocyte surface glycoproteins, or chelate divalent cations. After this initial attachment phase, lymphocytes enter apical clefts between endothelial cells where they assume a motile configuration characterized by loss of microvilli and formation of irregular surface folds. Intramural lymphocytes adhere to adjacent endothelial cells through macular and villous contacts. Fibrillar electron-dense material traverses the 15-20 nm gap at these points of adhesion. Microtubules and microfilaments are also seen around areas of cytoplasmic constriction in these motile lymphocytes. The migrating lymphocytes show cytoplasmic polarity which is oriented in the direction of movement as they pass through extracellular spaces in the venular wall and cross successive laminations in the perivascular sheath to enter the node. Since these lymphocytes enter channels between endothelial cells which are stained by intralymphatic injections with horseradish peroxidase, it is suggested that their entry into the node depends upon migration along a chemotactic gradient.
Microvascular changes in lymph nodes draining skin allografts.
Histological, histochemical, ultrastructural, and radiolabeling characteristics of the microvasculature in regional nodes draining skin allograft sites are described. From 12 to 48 hours after grafting, these nodes show increased vascular permeability and altered lymphocyte traffic pattern. The rapid rise in lymphocyte migration indices and the apparent plugging of intermediate sinuses by lymphocytes suggest that both increased entry and decreased egress of recirculating cells contribute in "lymphocyte trapping." This is followed by redistribution of cortical capillary arcades as existing germinal centers dissolve and proliferating lymphocytes infiltrate the cortex. Normal microvascular patterns reappeared at 7 to 14 days as primary and secondary nodules form in the enlarged nodes. Increased length and arborization of high endothelial venules resulted from focal proliferation of endothelial cells in transition zones from high to low endothelium. In stimulated nodes, high endothelial cells exhibit increased cytoplasmic basophilia and acid hydrolase activities which correlate with the appearance of numerous polyribosomes, RER cisternae, and lysosomes in their cytoplasm. These "activated" endothelial cells phagocytose microthrombi within venular lumens.
Studies on the structure and permeability of the microvasculature in normal rat lymph nodes.
The structure and permeability of the microvasculature in normal rat lymph nodes was studied by regional perfusion techniques. The results indicated that characteristic vascular units supplied each cortical lobule of lymphatic tissue. Numerous arteriovenous communications and venous sphincters innervated by unmyelinated nerve fibers were found in this vascular bed. These specialized vascular structures permitted regional control of blood flow through high endothelial venules. Lymphocytes migrated across these venular walls by moving through intercellular spaces in the endothelium and between gaps in the laminated, reticular sheath. No direct anastomoses between blood vessels and lymphatics were seen, but tracer studies with horseradish peroxidase suggested that functional lymph node-venous communications were present in the walls of high endothelial venules.
Immunosuppressive effects of chronic drainage of the thoracic duct in rats.
Explore the source record for details and available documents.
Immunologic studies of prolonged thoracic duct cannulation in rats.
Explore the source record for details and available documents.
In vivo studies on the intravascular changes produced by antilymphocyte serum.
Explore the source record for details and available documents.
The effect of heterologous anti-lymphocyte seerum on mouse hemopoietic stem cells.
The present study has demonstrated that rabbit anti-mouse lymphocyte serum (RAMLS) has the capability of destroying bone marrow cells and suppressing hemopoietic stem cell function. The in vitro incubation of bone marrow suspensions with RAMLS caused extensive cell lysis with an apparent preferential destruction of lymphoid, erythroid, and blastoid elements. Using the spleen colony assay, the number of functional hemopoietic stem cells was found to be markedly reduced in bone marrow populations exposed to RAMLS in vitro. Further, this loss of stem cell function could be produced by exposing marrow suspensions to small concentrations of antiserum which did not produce detectable cytotoxic effects on the general marrow population. A similar effect of RAMLS upon hemopoietic stem cells was found in vivo. The intravenous injection of RAMLS into lethally irradiated mice immediately after the infusion of isogeneic marrow cells reduced the number of spleen colonies formed, indicating that the antiserum could exhibit a deleterious effect upon stem cells in the bloodstream of the intact animal. Normal animals treated with daily subcutaneous injections of RAMLS for 3 wk had a significantly reduced marrow content of functional hemopoietic stem cells, suggesting that RAMLS can affect stem cells located in situ in the bone marrow. The experiments indicate that RAMLS possesses potential marrow toxicity.
The potential bone marrow toxicity of antilymphocyte serum in mice.
Explore the source record for details and available documents.
Intravascular thrombosis and leukocyte destruction in vivo by heterologous antilymphocyte serum.
Explore the source record for details and available documents.