Possible involvement of activator protein-1 DNA binding in mechanisms underlying ischemic tolerance in the CA1 subfield of gerbil hippocampus.

Transcription factors are nuclear proteins with an ability to recognize particular nucleotide sequences on double stranded genomic DNAs and thereby modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNAs in cell nuclei. Gel retardation electrophoresis revealed that transient forebrain ischemia for 5 min led to drastic potentiation of binding of a radiolabelled double-stranded oligonucleotide probe for the transcription factor activator protein-1, in the thalamus as well as the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of the gerbils previously given ischemia for 2 min two days before, which is known to induce tolerance to subsequent severe ischemia in the CA1 subfield. By contrast, ischemia for 5 min resulted in prolonged potentiation of activator protein-1 binding in the vulnerable CA1 subfield of the gerbils with prior ischemia for 5 min 14 days before, which is shown to induce delayed death of the pyramidal neurons exclusively in this subfield. Similar prolongation was seen with activator protein-1 binding in the vulnerable thalamus but not in the resistant CA3 subfield and dentate gyrus of the gerbils with such repeated ischemia for 5 min. Limited proteolysis by Staphylococcus aureus V8 protease as well as supershift assays using antibodies against c-Fos and c-Jun proteins demonstrated the possible difference in constructive partner proteins of activator protein-1 among nuclear extracts of the CA1 subfield obtained from gerbils with single, tolerated and repeated ischemia. These results suggest that de novo protein synthesis may underlie molecular mechanisms associated with acquisition of the ischemic tolerance through modulation at the level of gene transcription by activator protein-1 composed of different constructive partner proteins in the CA1 subfield. Possible participation of glial cells in the modulation is also suggested in particular situations.

Autologous blood transfusion using recombinant human erythropoietin in radical hysterectomy.

The possibility of serious complications of infection and GVHD and adverse prognosis in cancer patients resulting from homologous blood transfusions has been reported. We used recombinant human erythropoietin (rHuEPO) in autologous blood transfusions for radical hysterectomies to avoid the risks associated with transfusions. rHuEPO efficacy, stability and influence on hemodynamics were investigated. All patients were able to donate 1,200 ml of autologous blood prior to surgery, and anemia did not result despite phlebotomy three times each week. Elevation in Hb concentration was calculated at 0.78 +/- 0.37 g/dl over the first 7 days, and 2.12 +/- 0.35 g/dl over the first 14 days. No adverse side effects were observed in any patient. The serum EPO level was measured by RIA, and compared to the homologous blood transfusion group. rHuEPO did not influence postoperative EPO secretion. Autologous blood transfusion with rHuEPO in radical hysterectomy was extremely effective in mitigating the risks associated with homologous blood transfusions.