Enhancement of CD3-mediated thymocyte apoptosis by the cross-linkage of heat-stable antigen.

Heat-stable antigen (HSA) is a murine differentiating antigen that is expressed on both CD4-CD8- double-negative and CD4+CD8+ double-positive thymocytes but not CD4+ or CD8+ single-positive thymocytes. Effects of anti-HSA monoclonal antibody, R13, on thymocyte apoptosis induced by various stimulations were investigated by a single-cell suspension culture system. Immobilized R13 enhanced the CD3-mediated DNA fragmentation and killing of thymocytes but not the dexamethasone-induced or phorbol myristate acetate-induced killing of thymocytes. Immobilized R13 by itself could not induce thymocyte apoptosis. Soluble R13 enhanced CD3-mediated apoptosis when HSA and T-cell receptor (TCR)/CD3 were co-cross-linked by a cross-reactive secondary antibody. Even without the cross-reactive secondary antibody, soluble R13 enhanced CD3-mediated apoptosis, although a greater than 100-fold increase in the amount of R13 was needed to give a similar enhancement compared with immobilized R13. Neither R13 by itself nor R13 plus secondary antibody induced cytosolic calcium influx, whereas R13 enhanced CD3-mediated cytosolic calcium increase. These results suggest a functional role of HSA in promoting the activation-induced apoptosis of thymocytes and the involvement of HSA in negative selection.     

Peripheral T-cell Lymphomas Immunologic and Enzyme Histochemical Analysis of 15 Cases

Ffteen cases of peripheral T cell lymphoma were studied to evaluate the respective properties of various histologic types using enzyme histochemical and ultrastructural examinations in addition to immunological methods. Eleven cases in an ATLA negative group manifested various histologic patterns such as IBL like, pleomorphic and Lennert's lymphomas in comparison with the relatively monomorphic proliferation of neoplastic lymphoid cells in the 4 ATLA positive cases. The presence of neoplastic clear cells is characteristic of peripheral T-cell malignancies, and is likely to be found in CD4 lymphomas. There is an occasional reaction of epithelioid histiocytes and plasma cells with eosinophils, the former being designated Lennert's lymphoma and the latter IBL like T-cell lymphoma. Immunological examination revealed four immunophenotypic patterns: (1) CD2⁺3⁺4⁺8⁺, (2) CD2⁺ 3⁻4⁺8⁻, (3) CD2⁺3⁺4⁻8⁺, and (4) CD2⁺3⁺4⁺8⁺, but did not provide information concerning the intimate relationship between histologic types and immuno phenotyes. β-Glucuronidase reactivity, however, contributed to the distinction between helper and suppressor T cell malignancies, suggesting its usefulness for distinguishing these two cell types and their malignant counterparts.     

Changes in the tumorigenic and metastatic properties of tumor cells treated with quercetin or 5-azacytidine

The effect of quercetin, a flavonoid derivative, on the transplantability (tumorigenicity) and metastatic behavior of mouse tumor cells was studied. BMT-11 c1-9 fibrosarcoma cells were treated in vitro with quercetin, and after cloning by limiting dilution, cell suspensions of each clone were injected subcutaneously (s.c.) into syngeneic C57BL/6 mice at a dose of 2 X 10(5) cells per mouse. Out of 17 clones examined, 8 were nontumorigenic in normal mice ("regressor" clones), whereas these clones were able to grow in immunosuppressed (600-rad-irradiated) mice. Furthermore, 1 out of 9 tumorigenic clones metastasized spontaneously to the lungs despite the very low metastatic potential of the parent BMT-11 c1-9 cells. In contrast, all 15 clones selected from the untreated parental line grew progressively in normal mice with no evidence of metastases. The appearance of both regressor and metastatic clones was also observed after treatment with a DNA hypomethylating agent, 5-azacytidine. These altered phenotypes resulting from treatment with both chemicals, however, were not necessarily stable if maintained in culture for several months. The data suggest that quercetin may be a useful new material for obtaining regressor or metastatic clones from parental tumor lines.     

Changes in circulating blood volume following isoflurane or sevoflurane anesthesia

Changes of circulating blood volume (CB volume) measured by the dual indicator dilution method were observed in 33 chronically instrumented mongrel dogs following either alpha-chloralose-urethane (C group), additive isoflurane (I group) or sevoflurane anesthesia (S group). These anesthetic groups were each divided into two subgroups with regard to respiratory care, namely Cp, Ip and Sp for those with intermittent positive pressure ventilation (six animals per subgroups), and Cs, Is and Ss for those with spontaneous breathing (five animals per subgroups).The CB volume under positive pressure ventilation remained unchanged in the Ip and Sp groups at both 0.5 and 1.0 MAC, and in the Cp group. The CB volume remained essentially unchanged in the Cs and Is groups at both 0.5 or 1.0 MAC, but the plasma volume tended to increase slightly in the Is group at 1.0 MAC.In the Ss group under spontaneous breathing, however, the CB volume increased from 84.4 ± 7.0 to 91.4 ± 7.7 at 0.5 MAC, and to 91.4 ± 10.2ml·kg^–1 at 1.0 MAC (0.01 P 0.05). These increases were caused by an increase in the plasma volume.The above data suggests that a concomitant increase in the venous pressure associated with an increase in the intrathoracic pressure produced by positive pressure ventilation would attenuate changes in the CB volume during sevoflurane anesthesia.(Hamada H, Takaori M, Kimura K, et al.: Changes in circulating Blood volume following isoflurane or sevoflurane anesthesia. J Anesth 7: 316–324, 1993)