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Biomedical subjects

D A Stewart

Publications and source records attributed to D A Stewart.

At least 91 records · Page 5Linked to original sources
PubMed1985

Hematopoietic colony-forming cells from mice after wound trauma.

The changes produced in the pluripotential and progenitor cell compartments of the hind leg bone marrow and spleen of skin-wounded mice were examined over a 2-week post-trauma period. Pluripotent cells (colony-forming unit-spleen, CFU-s) were significantly increased in the spleen and slightly reduced in the leg marrow the first week after trauma. Granulocyte macrophage colony-forming cells (GM-CFC) were significantly increased in the spleen throughout the 2-week period and were increased in the leg marrow during the first post-trauma week. Macrophage colony-forming cells (M-CFC) were significantly decreased in the spleen during the 2-week period and were slightly elevated in the leg marrow during that time. The peripheral blood contained significantly increased concentrations of CFU-s and GM-CFC but not M-CFC. Serum of wounded mice supported growth of GM-CFC but not M-CFC. The growth-promoting factor was extractable by CHCl3 treatment. Serum C-reactive protein concentrations were significantly increased for a 5-day period after wound trauma.

Animals↗
PubMed1984

Characteristics of lympho-myelopoietic stem cells isolated from canine peripheral blood.

If hematopoietic stem cells (HSC) could be separated from peripheral blood, it might be possible to harvest these stem cells for potential clinical use. By leukapheresis techniques, we harvested mononuclear cells (MNC) from peripheral blood and then placed these cells over discontinuous stractan gradients of three densities (1.077 gm/ml, 1.071 gm/ml and 1.066 gm/ml). These separated cells were submitted to colony culture to identify colony-forming-unit activity for granulocyte-macrophage (CFU-C) and T-cell lymphocyte (CFU-L) cell lines. The lightest cells (1.066) contained most of the CFU-C and no CFU-L activity. Heavier cells (greater than 1.071) contained CFU-L and very little CFU-C activity. CFU-L colonies could be distinguished from CFU-C by their density and distinct morphological appearance. In addition, the amount of CFU-C could be increased in the animal by increasing the amount of blood processed (from 3.9 +/- .76 CFU-C/10(6) MNC to 6.7 +/- .35 CFU-C/10(6) MNC). This resulted in an increase of CFU-C collected from 7.6 +/- 2.1 CFU-C/10(6) MNC after the first equivalent blood volume to 22.5 +/- 3.4 CFU-C/10(6) MNC after the third equivalent blood volume processed. These results suggest that leukapheresis and gradient density separation may be useful procedures to obtain HSC.

Animals↗
PubMed1983

Granulocyte progenitor cell (CFUC) harvest by continuous apheresis in dogs. Effects of blood volume and lithium on yields.

The ability to harvest large amounts of hematopoietic stem cells from blood would eliminate the more difficult approach of bone marrow harvest. Unfortunately, concentration of stem cells in the blood compartment is less than 1% of their concentration in bone marrow. Attempts to increase harvest of blood stem cells, as assayed by granulocyte progenitor cells (CFUC), have been only partially successful. Our study confirms previous reports that CFUC can be mobilized into the blood compartment in dogs, but this mobilization is rate-limited. Unlike platelets and granulocytes that are effectively harvested during the first blood volume processed by continuous apheresis, effective CFUC harvest begins during the second blood volume (606 +/- 97.9 CFUC/ml), peaks by the third (740 +/- 30 CFUC/ml), and remains constant through five blood volumes processed (700 +/- 272 CFUC/ml). Since blood CFUC concentration falls at the end of five blood volumes processed (40% of initial values), further continuous apheresis would not be effective. Treatment of animals with lithium did not improve CFUC harvest. These results show that apheresis procedures can be developed to a limited extent to increase the harvest of hematopoietic progenitor and stem cells.

Animals↗
PubMed1981

Skin wound-enhanced survival and myelocytopoiesis in mice after whole-body irradiation.

Skin wounding at 24 h before whole-body 60Co irradiation of mice raised the LD50/30 from 8.09 to 9.71 Gy resulting in a dose reduction factor of 1.2. Concentrations and quantities of myeloproliferative cells were examined at 3, 7, 10, and 14 days after 7 Gy, skin wounding 24 h before 7 Gy and in control non-treated mice. Wounding before irradiation provoked an increase in marrow and splenic clonogenic cells that was earlier and greater than that noted for irradiated mice. Supranormal levels of splenic CFu-s and CFU-c were found in animals wounded before irradiation. M-CFC values were depressed throughout, although greater for combined injured animals than for irradiated mice.

Animals↗
PubMed1980

Proliferative responses of lympho-myelopoietic cells of mice after wound trauma.

The hypothesis that wound trauma produces either selective or total organ cell population alterations in the quantities of lympho-myeloproliferative elements in the major hematocytopoietic centers was tested. Mice were subjected to a 4% body surface skin wound on the anterior dorsum; their tissues were assayed 24 hours later for their total cellularity and proliferative potential. In wounded mice, the marrow cellularity was significantly decreased but this did not result in lower stem cell (CFU-s) and progenitor cell (CFU-c and M-CFC) quantities. However, there were significant selective and total population reductions in cells responsive to T and B cell mitogens. Splenic cellularity and stem cell quantities in wounded mice did not differ from control-treated animals. However, there were both selective and total population reductions in splenic CFU-c and M-CFC. Wounding resulted in a greater splenic T cell response to phytohemagglutinin PHA, while the responses to concanavalin-A (CON-A) were similar to controls. The splenic B lymphocyte population was specifically increased. Wounding resulted in a significant thymic hypocellularity. This was mirrored by a selective decrease in M-CFC and a total cell population reduction in response to T cell mitogens.

Animals↗
PubMed1980

The additive protective effects of hypothermia and chemical cardioplegia during ischemic cardiac arrest in the rat.

In a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest the potential additive protective effects of hypothermia and chemical cardioplegia have been investigated. Isolated rat hearts were subjected to a 2 minute period of coronary infusion with a cardioplegic or a noncardioplegic solution immediately before and also at the midpoint of a 2 hour period of hypothermic (20 degrees C) ischemic cardiac arrest. In the hypothermia plus cardioplegia group postischemic aortic flow recovered to more than 50% of its preischemic control value, myocardial energy phosphate content returned to near preischemic control levels, and creatine kinase leakage was moderate. By contrast, in the hypothermia alone group (coronary infusion with non cardioplegic solution) the postischemic functional recovery was less than 30% of its preischemic control value, cellular high-energy phosphate content was considerably reduced, and creatine kinase leakage was more than twice that observed in the hypothermia plus cardioplegia group. In addition to illustrating the additive nature and powerful protective properties of hypothermia and cardioplegia these studies serve to illustrate the utility of the isolated rat heart model for the primary assessment of procedures designed to protect the myocardium during ischemic cardiac arrest. The results and conclusions derived from this study were quantitatively and qualitatively similar to those obtained in a parallel study in the dog.

Adenosine Triphosphate↗
PubMed1979

Inotropic agents and functional recovery from ischemic cardiac arrest.

Short periods of ischemic arrest may cause myocardial cell damage so that reperfusion does not result in an immediate return to normal metabolic and contractile activity. Studies have been carried out using a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest in order to determine whether the use of inotropic agents (isoprenaline and dobutamine) to augment contractile activity during the early phase of post-ischemic reperfusion extends pre-existing damage and results in ultimate impairment of contractile activity. The results indicated the existance of a substantial metabolic reserve, capable of providing sufficient energy for a marked increase in dP/dt and heart rate, without inducing tissue damage. However, in this isolated rat heart preparation the use of these agents had relatively little effect upon cardiac output and could be shown to induce a dose-dependent reduction in stroke volume.

Animals↗
PubMed1978

Myocardial susceptibility to ischemic damage: a comparative study of disease models in the rat.

Using experimental models of various disease states, the ability of the isolated perfused working rat heart to withstand and recover from a period of severe ischemia was investigated. The results revealed that the coexistence of a diabetic state, obesity, or left ventricular hypertrophy increased the susceptibility of the hearts to ischemic damage and reduced the rate or the extent of postischemic recovery. In contrast, hearts obtained from moderately hypertensive rats exhibited a greater resistance to, and a superior recovery from, ischemia than did hearts obtained from normotensive controls.

Adenosine Triphosphate↗
PubMed1978

Myocardial protection during ischemic cardiac arrest. The importance of magnesium in cardioplegic infusates.

The increasing use of coronary infusates for the protection of the human heart drug ischemic cardiac arrest has placed great emphasis on the need for a rational and safe formulation of any infusion solution. Using a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest, we have found magnesium to be a highly effective component of protective infusates which can be additive to hypothermia and other protective agents. However, the concentration of magnesium bears a complex relationship to the degree of protection, a fact which stresses the need for the establishment of the correct concentration for optimal protection.

Animals↗
PubMed1978

Myocardial protection during ischemic cardiac arrest. Possible deleterious effects of glucose and mannitol in coronary infusates.

Cardioplegic protective infusates are designed to induce rapid diastolic arrest and also to reduce or delay the onset of ischemic damage. As this study shows, the use of such infusates can greatly improve postischemic recovery of cardiac function. A number of investigators include glucose, insulin, or mannitol in their infusates in an attempt to increase the amount of protection afforded to the ischemic myocardium. Using an isolated, working rat heart model of cardiopulmonary bypass and ischemic cardiac arrest, we have shown that under certain conditions these additives can be deterimental to tissue protection. The deleterious effects of glucose and mannitol are dose dependent and can be modified by the inclusion of insulin in the infusate. The damaging effects of glucose appear to be both osmotic and metabolic in origin and those of mannitol, purely osmotic. The effects of insulin are complex and may affect a number of cellular processes.

Animals↗
PubMed1978

Early development of children with sex chromosome aberrations.

A prospective study was made of 42 children who were found at birth to have sex chromosome aberrations. The mean developmental quotient of the XXY and XXX groups was in the dull-normal range, whereas developmental quotients of 3 XYY children were low normal. The commonest deficits were in language and gross motor skills, with highest incidence in the XXX group. Many of the children had behavior problems, but no specific pattern was associated with an individual chromosome aberration. The XXX group experienced a linear growth spurt after 4 years of age. With one exception there were only mild dysmorphic features, none of them specifically associated with any subgroup. Of 17 children followed up to school age, almost two thirds evidenced learning and/or behavior problems. There was a high incidence of birth problems particularly in XXX children (seven of ten), and of social problems, psychiatric illness and learning difficulties in their families. In 14 cases, the parent-child relationship was disturbed, resulting in behavior problems. These findings make it improbable that the children's generally poor developmental and behavioral performance were solely attributable to their chromosomal constitution.

Child, Preschool↗