In this report we studied the mechanism of the immunodeficiency of the recipients grafted with allogeneic bone marrow. The results indicated that the IL-2 production of ABMT mice was seriously impaired. Further investigation revealed that the spleen cells of ABMT mice were able to suppress GVHD in the lethally irradiated BALB/c mice. After removing the T cells, the spleen cells of ABMT mice lost this inhibitory effect. Furthermore, the supernatant of the spleen cell culture of ABMT mice is able to inhibit the mixed lymphocyte reaction, the IL-2 production and the killing activity of the CTL of normal BALB/c mice. After removal of T cells, the supernatant of the spleen cell culture lost its inhibitory effect. These results suggested that the increased activity of T suppressor secreting a non-specific suppressor factor might be an important mechanism of the immunodeficiency of ABMT mice.

The synergistic effect of combinations of killing agents on tumor cells has long been recognized. Fodstad et al, reported that the combinations of Ricin and Adriamycin have a strong, syn ergistic effect on the L1210 leukemia cells. In this report, a novel immunotoxin containing Ricin and Adriamycin, BDI-l-Ricin-Adriamycin, was described.Ricin and Adriamycin were chemically coupled onto one monoclonal antibody molecule against human bladder cancer, BDI-1, to construct the two-killing-agent containing immunotoxin. The results of indirect immunofluorescence test and competiton bindig assay showed that the retention of 70% of the antibody binding activity in this immunotoxin was obtained. The in vitro cytotoxicity assay indicated that the immunotoxin in the presence of 0.1M galactose is 30,000 times more cytotoxic than BDI-1-Adriamycin conjugate and 10 times more cytotoxic than BDI-1-Ricin immunotoxin in the bladder cancer-specific killing, but has no cytotoxic effect on the LOVO colon carcinoma cells. This two-killing-agent containing immunotoxin may lead to the development of a new kind of immunotoxins which have strong cytotoxic activity to target cells.

In this study the effect of rIL—6 on the immunological reconstitution of mice following bone marrow transplantation(BMT)was evaluated.The lethally irradiated(950Rad)BALB/c mice engrafted with BMT were injected ip with rIL—6(1000 ug/kg)on day 2.At day 30 after BMT the proliferative responses to ConA and LPS,the mixde lymphocyte reaction(MLR)and the activity of cytotoxic T lymphocytes(CTL)to the allogeneic splenic cells(C57BL/6),and the numbers of plaque forming cells(PFC)to SRBC were significantly enhanced in the rIL—6 treated recipient mice,as compared to that in the control BMT mice.In the BMT mice following 10 day rIL—6 treatment,the above immune functions on day30 after BMT were recovered to the immunological condition of the control BMT mice on day 60,suggesting that the rIL—6 is able to accelerate the process of immunological reconstitution of BMT mice.

Sublethally irradiated BALB/c mice undergo thymic regeneration which follows a pheno-typic pattern of events similar to that observed during normal fatal development the regenerationafter irradiation is the result of a limited pool of intrathymic radioresistant stem cells.In this study we showed that 6?10~5u/kg IL-2 can accelerate the proliferation of thymo-cytes,improve the development of thymocytes from CD4~-CD8~-to CD4~+CD8~+ and CD4~+CD8~-/CD4~- CD8~+.At 30th day after irradiation,the proliferative responses of the splenocytes to ConAand LPS,the mixed lymphocyte reaction (MLR) to allogeneic spleen cells (C57BL/6),and thenumbers of plaque forming cells to SRBC were significantly enhanced in IL-2 treated mice,ascompared to that in the irradiated mice without giving IL-2.The above immune functions on day30 after irradiation were recovered to the condition of irradiated control mice on day 45,suggest-ing that the IL-2 is important cytokin in the development of thymocytes in thymus and is able toaccelerate the recovery of immune functions of irradiated mice.

Objective To investigate a clinically perspective way of inducing transplantation tolerance. Methods Kidney transplantation model was established using Lewis (RT1 l) rats as recipients and DA (RT1 a) rats as donor. Before transplantation the recipient rats were conditioned with anti lymphothyte serum (ALS) injected for three times, followed by 10 8 donor bone marrow cells transfusion (BMT) and injection of 100 mg/kg cyclophosphamide (CP), survival time of kidney allografts, mixed lymphocyte reaction (MLR) and delayed type hypersensitivity (DTH) of recipient to donor spleen cells were observed and studied. Results 5 of the 7 kidney allografts survived 73 to 90 days without sign of rejection. The donor specific MLR and DTH were suppressed. Conclusions Induction of transplantation tolerance is a prospective way for the prevention of allograft rejection.

The mechanisms of immunosuppression of TWH were studied. The results indicated that TWH was able to reduce the antibody forming cells of splenocytes in mice and to suppress directly the proliferation of B cells to lipopolysaceharide ( LPS ) and to decrease the production of IL-2. Furthermore, TWH was able to produce immu-nosuppressive effect by activiting Ts cells.

Objective:To explore the involvement of endoplasmic reticulum molecular chaperone GRP78 in the impairment of inner ear consistented with the mimetic aging model.Method:Twenty-four Wistar rats were randomly divided into two groups. model group was in duced by daily hypodermic injection of 10% D-galactose (800 mg·kg~(-1)·d~(-1)) for 8 weeks and the control group was given saline accordingly. Spatial learning and memory was measured by Morris-Water-Maze. Colorimetry was used to analyze superoxide dismutase (SOD) and malondialdehyde (MDA) extracted from inner ear tissue. Hearing threshold of rats were detected with Auditory brainstem response (ABR).In addition, expression of GRP78 in the inner ear was detected by immunohistochemistry,RT-PCR and Western blot. The control group was studied parallel.Result:The escape latency in the model group injected with D-galactose was markedly longer than that in the control group.accordingly ,the changes of SOD and MDA were more significant in the model group, the difference between two groups was significant(t-test,P<0.01). the variation of ABR in two groups was observed, There was no statistically difference of the hearing in the model group compared with the control group(P>0.05). The expression of GRP78 was significantly different between two groups ,which is increased in the inner ear tissue of model group(P<0.01).Conclusion:The impairment of inner ear tissue partly dued to the oxidative stress in the model, which was induced by D-galactose.and endoplasmic reticulum molecular chaperone was thought to contribute to the impairment mechanism of inner ear in mimetic aging model.

Arsenic trioxide albumin microspheres (As2O3-BSA-NS) were prepared by using methods of chemical cross-linking. The desirability function (DF), calculated according to the size (<1 microm) distribution, drug loading and drug trapping efficiency, was introduced as a total index for the microspheres formulation. Four factors, inculding W/O ratio, decentralization speed, BSA concentration and stirring stabilization time, were selected and arranged in an orthogonal experimental table. The release characteristic was studied by the drug release experiment in vitro. The four factors affected DF differently. Decentralization speed behaved as the maximum (P<0.01), followed by BSA concentration (P<0.05) and the W/O ratio dose (P<0.05). Stirring stabilization time did not influence DF (P>0.05). The release experiment in vitro showed that As2O3 in As2O3-BSA-NS was released more slower than pure As2O3. It was concluded that regular As2O3-BSA-NS may be prepared by the methods of chemical cross-linking, which was optimized by orthogonal experimental analysis of different factors, and the microspheres can release As2O3 slowly.
Arsenicals/*chemistry ; Cross-Linking Reagents/pharmacology ; Delayed-Action Preparations ; Drug Carriers/*chemistry ; Drug Delivery Systems ; Microspheres ; Oxides/*chemistry ; Serum Albumin, Bovine/*chemistry ; Technology, Pharmaceutical

Objective To study the changes of acetyl-histone H2B in the cochlear hair cells of the guinea pig model of noise-induced hearing loss (NIHL).Methods Sixty guinea pigs were randomly divided into control and noise-exposure group.Thirty guinea pigs in the noise-exposure group were exposed to narrowband noise at 122 dB SPL for 3 hours , while thirty guinea pigs in the control group were not exposed to noise.Auditory thresholds were assessed by auditory brainstem response (ABR), prior to noise in two groups and 3, 7,14 and 21 days after noise exposure in the noise group.Then we investigated the expression of acetyl-histone H2B levels in the sensory cells of basilar membrane after noise expose by immunofluorescence staining and western blot.Results Compared with pre-exposure hearing, ABR thresholds were increased at 1h, 3, 7, 14 and 21 days after noise exposure, and recovered gradually with time and reached a permanent threshold shift at 14 days.The expression of acetyl-histone H2B was down-regulated in the hair cells and Hensen''s cells of the guinea pig cochlea after the noise expose , The ratio of H2B-AcK5 / β-actin was 0.6179±0.1260 in the control group and 0.3102±0.0839 in the noise group, and the difference was statistically significant (P<0.01).Conclusion Noise decreased the inner ear sensory cells histone acetylation level and histone acetylation imbalance may be involved in the occurrence of NIHL.

Objective: To explore the role of anti-?? T cell receptor(TCR) and anti-CD80 monoclonal antibodies(mAbs) combined with donor bone marrow cells(BMCs) infusion in the induction of murine skin allografts tolerance.Methods: On day 0,2?10~8 BMCs of BALB/c mice were injected into recipient C57BL/6 mice via the tail vein,meanwhile,an intraperitoneal injection of TCR?? mAb(500 ?g) was given.On day 2,CD80 mAb was administered intraperitoneally.Skin grafting was performed on day 6.Delayed type hypersensitivity(DTH),mixed lymphocyte reaction(MLR),IL-2 reverse assay of MLR,adoptive transfer assay and chimerism detection were performed at different time points and tolerance mechanisms were investigated.Results: The mean survival time(MST) of BALB/c skin allografts in C57BL/6 recipients that were treated by anti-TCR?? and anti-CD80 mAbs combined with donor BMCs infusion was 70 days.DTH and MLR assay indicated that the tolerant mice displayed significant hyporesponsiveness.The result of IL-2 reverse test showed that clone anergy was probably involved in the formation of tolerance in the tolerant C57BL/6 mice.In vivo and in vitro adoptive transfer assay,suppressive activity in the spleens of tolerant C57BL/6 mice was observed.Chimerism existed in both the thymus and spleen of the tolerant C57BL/6 mice.The chimerism level gradually declined with time.Conclusion: Treatment of anti-TCR?? and anti-CD80 mAbs combined with donor BMCs infusion can successfully induce a long-term tolerance in BALB/c mice to C57BL/6 skin graft.Multiple mechanisms,including clone anergy,suppressor cells and chimerism are involved in the tolerance.