Leukocyte trafficking in response to magnetic resonance imaging.

There were significant increases in total T cells and in T helper cells in blood samples collected immediately following magnetic resonance imaging (MRI) examinations of brains of male volunteers and patients. Percentages of total lymphocytes and suppressor/cytotoxic T cells decreased in these same samples. There were no significant changes in any leukocyte subpopulations in males undergoing lumbar MRI and females undergoing brain MRI. Thus, it is unlikely that stress from the procedure is the explanation for these changes. Our results show that MRI has specific effects on a brain system(s) that controls lymphocyte subpopulations.

Radiation-induced clastogenic plasma factors.

Ionizing irradiation induces chromosomal aberrations in directly exposed cells and is known to have mutagenic and carcinogenic potential for the exposed host. Under controlled conditions, we examined whether such clastogenic effects of irradiation might be due in part to radiation-induced plasma factors. Irradiated cells and sera from CF-Nelson rats were used at 15 min, and 1, 7, 14, and 56-70 days after total body irradiation (250 R, n = 67 or 400 R, n = 39). Control rats (n = 44) served as donors of nonirradiated sera and cells. In addition, sera from six rats were irradiated (250 R or 400 R) in vitro. On the average, 298 metaphases from six rats were studied at each time-point. Cytogenetic abnormalities observed included chromatid- and chromosome-type lesions and hyperdiploidy. The frequency of abnormalities was comparable at both radiation doses. Nonirradiated cells exposed in vitro to irradiated serum (15 min postirradiation) exhibited a 36- to 48-fold increment in hyperdiploidy (p = 0.0001) and a 2.- to 2.2-fold rise in chromatid gaps and breaks (p less than 0.01), but none of the chromosome-type aberrations seen in cells exposed to radiation. The clastogenic activity of irradiated plasma persisted in circulation for the 10-wk duration of the study and was not abrogated by dilution with nonirradiated serum. Serum irradiated in vitro was not clastogenic. This study shows that irradiation of rats results in the prompt appearance of clastogenic activity in their plasma. This activity is not due to radiation-induced depletion of protective factors nor to chemical-physical changes of normal plasma components, but results from circulating factors released by irradiated cells.

Alterations in tissue glutathione levels following traumatic shock.

Many of the metabolic and physiologic alterations that develop in normal rats following whole-body trauma are not observed in rats made resistant to this stress by their prior exposure to sublethal episodes of trauma. These trauma resistant (TR) animals survive high doses of trauma that produce lethal traumatic shock if given to normal animals. This laboratory has studied several biochemical events following trauma in naive and resistant rats to better understand the cellular events in shock and the mechanism of resistance to this severe injury. In the present studies glutathione (GSH) levels in the kidney, liver, and spleen were determined at various time intervals after trauma in normal and TR rats. In normal rats 1.5 hr after trauma, there was a significant decrease in kidney, liver, and spleen GSH levels. In the kidney these returned to normal at 4 hr and increased above controls at 24 hours. In the liver GSH remained low at 4 hr and increased above controls at 24 hours. In the spleen levels returned to normal at 4 hr and remained constant throughout the time of observation. In TR rats no changes were seen in the kidney and an increase above normal values occurred at 48 hr in the spleen. In the liver of TR rats there was an early drop in the GSH levels, but these returned to normal at 4 hr and rose significantly at 24 hours. Alterations in the concentration of glutathione, a physiologically important non-protein sulfhydryl compound, may represent a mechanism by which cellular adjustment of the body occurs to stress and environmental agents.

RES and immune suppression in traumatic shock.

Stimulation of reticuloendothelial function was previously shown to protect against the consequences of traumatic shock, but paradoxically RE stimulation appeared to decrease the number of antibody-forming cells that developed from immunization with heterologous erythrocytes. A decrease in the number of hemolytic plaque-forming cells (PFC) was absent in trauma-resistant animals, whereas an increased number of cells was produced by impairing the phagocytic activity of RE cells. In order to determine whether phagocytic or adherent cells from rat spleen cell preparations were suppressing the PFC response, macrophages were removed with a magnet after incubating with carbonyl iron powder for one hour. Control cultures were prepared with mixed spleen cells. The hemolytic plaque-forming capacity increased 50-fold from control mixed spleen cultures as compared to those from which spleen macrophages were removed. The addition of an equal number of adherent phagocytic cells to cultures of macrophage-depleted spleen cells prevented this increase. Macrophages present in the spleen appear to be responsible for this low PFC response in the rat and may suppress the antibody-forming cell response to TR rats.

Histamine biosynthesis in shock.

The histidine decarboxylase activity of the lung and spleen was determined in rats made resistant to trauma either by prior sublethal exposure or by injection of extracts prepared from the spleens and plasma of trauma-resistant rats. The data describe the posttraumatic period in the normal animal as being associated with an increased histidine decarboxylase activity. In trauma-resistant animals, changes in the enzyme activity were prevented in the lung and were less pronounced in the spleen. The administration of extracts from trauma-resistant rats was similarly effective in impeding the changes in enzyme induction following trauma. It is suggested that an active humoral factor previously shown to be elaborated during conditioning and associated with the RES may act by inhibiting the activation of histidine decarboxylase.

Histidine decarboxylase activity in trauma-resistant rats.

Studies have been carried out to determine the possible role of nascent histamine in the development of traumatic shock. This was done by examining histidine decarboxylase (HD) activity of the lung, spleen, and plasma following exposure to trauma in normal and trauma-resistant rats. In normal rats, there was a significant increase in lung HD activity at 15 min and 4 h; and in the spleen the HD activity increased significantly at 4 h. In trauma-resistant rats exposed to trauma, there were no changes in enzyme activity in the lung and less pronounced changes in the spleen. The plasma HD activity remained stable in normal and resistant rats following episodes of trauma. Changes in total erythrocyte hemoglobin were observed in both normal and trauma-adapted rats following exposure to this stress, increasing significantly in normal rats, but decreasing in trauma-resistant rats. Blood volume decreased significantly at 4 h after trauma in normal animals; whereas only a slight decrease was noted in resistant animals. The data support the concept that newly formed histamine contributes to the pathogenesis of shock. It is also proposed that the increased resistance, characteristic of trauma-adapted rats, could be partly due to an inhibition of enzyme activation following trauma.

Trauma induced histamine synthesis and RES activity.

The histidine decarboxylase activity of the lung and spleen was determined in animals made resistant to tumbling trauma, either by prior sublethal exposure or by injection of extracts prepared from the spleens and plasma of trauma resistant rats. The data describe the post-traumatic period in the normal animal as being associated with an increased histidine decarboxylase activity. In addition, the increased histidine decarboxylase activity was paralleled by an increased phagocytic activity of the reticuloendothelial elements of the spleen. In trauma resistant animals, changes in the enzyme activity and phagocytic capability were prevented or curtailed. The administration of spleen and plasma protective extracts were similarly effective in impeding these changes following trauma. It is suggested that the active humoral factor elaborated during conditioning and associated with the RES may act by inhibiting the activation of histidine decarboxylase.