Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics

Inhaled anesthetics have been shown to increase the aggregation of amyloid beta in vitro through the stabilization of intermediate toxic oligomers, which are thought to contribute to neurocognitive dysfunction in Alzheimer's disease. Inhaled anesthetics may escalate cognitive dysfunction through enhancement of these intermediate oligomer concentrations. We intermittently exposed 12-month-old Tg2576 transgenic mice and nontransgenic littermates to isoflurane and halothane for 5 days. Cognitive function was measured before and after anesthetic exposures using the Morris Water Maze; amyloid beta plaque burden and caspase-3 mediated apoptosis were quantified by immunohistochemistry. At 12 months of age, anesthetic exposure did not further enhance cognitive decline in the transgenic mice. Immunohistochemistry, however, revealed that the halothane-exposed Tg2576 mice had more amyloidopathy than the isoflurane treated mice or the nonexposed transgenic mice. Isoflurane exposure impaired cognitive function in the nontransgenic mice, implying an alternative pathway for neurodegeneration. These findings indicate that inhaled anesthetics influence cognition and amyloidogenesis, but that the mechanistic relationship remains unclear.     

Terminal deoxynucleotidyl transferase-containing cells in peripheral blood: implications for the surveillance of patients with lymphoblastic leukemia or lymphoma in remission

An indirect immunofluorescence assay was used to quantitate TdT- containing (TdT+) cells in the mononuclear leukocyte fraction of peripheral blood from normal subjects and patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). In normal children (10) and adults (10), 0.036% +/- 0.014% (mean +/- SD) and 0.030% +/- 0.015% TdT+ cells were found. In peripheral bloods from 10 children receiving chemotherapy for tumors other than ALL or LL, 0.040% +/- 0.039% TdT+ cells were found. Serial determinations were performed on 15 patients with ALL or LL who were in clinical remission. Eight of these patients remained in continuous remission and always had fewer than 0.11% TdT+ cells in their peripheral blood. Three patients who developed systemic relapse were found to have progressively rising numbers of TdT+ cells in their peripheral blood prior to clinical evidence of relapse. All 3 of these patients had greater than 0.1% TdT+ cells in their peripheral blood from 3 to 8 wk prior to clinical relapse. In 3 other patients, localized extramedullary relapse developed, but no trend was found on serial TdT determinations. Thus, the indirect immunofluorescence assay for TdT detects a small population of cells in normal peripheral blood. In patients with ALL, progressive increases above this normal level were associated with subsequent bone marrow relapse.