OBJECTIVETo study the effect of total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the role of CD4(+)CD25(+) regulatory T cells on induction of immunotolerance in the recipient.

METHODSLiver transplantation was performed using male Lewis rats as donors and male DA rats as recipients. These rats were randomly allocated into the following groups:Control group, Homogeneity Liver Transplantation group, Idio-immunotolerance group and Acute Rejection group. After transplantation, survival time rate of each group were observed. Serum ALT, TB level, Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of GITR on T cell subgroup, histopathology of the hepatic graft on day 14, spleen CTL lytic activity on day 14 were measured.

RESULTSIn the Idio-immunotolerance group, the recipients suffered from transient rejection after surgery but acquired immunotolerance and survived long. In the Acute Rejection group, the donors were preconditioned with total body irradiation before liver transplantation. All recipients died between day 17 to 21. Serum ALT and TB increased significantly and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly compared with the Idio-immunotolerance group, the Homogeneity Liver Transplantation group and the Control group. The expression of GITR on CD3(+)CD4(+)T cells in the peripheral blood decreased, the expression of GITR on CD3(+)CD8(+) T cells and CTL lytic activity of the recipients increased by preconditioning of the donors with total body irradiation.

CONCLUSIONSPreconditioning of the donors with total body irradiation eliminated the passenger lymphocytes of the liver graft, decreased the expression of Foxp3(+)CD4(+)CD25(+) regulatory T cells in peripheral blood, and increased the expression of GITR on CD3(+)CD8(+) T cells, thus affected the course of tolerance and induced acute rejection after liver transplantation.

Animals ; Liver Transplantation ; immunology ; Male ; Rats ; Rats, Inbred Lew ; T-Lymphocytes, Regulatory ; immunology ; Tissue Donors ; Transplantation Conditioning ; Transplantation, Homologous ; immunology ; Whole-Body Irradiation

Human-landing catch (HLC) technique was undertaken in nine selected study sites within Peninsular Malaysia to determine the biting cycle of Aedes, Armigeres, Culex, and Mansonia mosquitoes. HLC was conducted 24 hours on three different nights in a duration of one week at each study site. Aedes albopictus were found in all study sites with bimodal biting cycle, whereas the biting peak of Aedes butleri was recorded between 1600 and 1900 hr. For Armigeres, five study sites demonstrated similar biting peak hour (1900 – 2000 hr) for Ar. kesseli four study sites showed biting peak at 1800 – 1900 hr for Ar. subalbatus. Culex quinquefasciatus was collected from all study sites except in Sungai Penchala with its biting activity beginning from 1900 hr. Both Mansonia annulifera and Mansonia uniformis captured in two different study sites showed similar biting peaks (1500 – 1600 hr). It is recommended that vector control activities be carried out at dusk as almost all mosquito species captured started their biting activities at that time.

OBJECTIVETo summarize the 8-year experience of radiofrequency ablation (RFA) on liver malignancies and explore the effect and prognostic factors.

METHODSFrom August 1999 to February 2007, 803 patients with liver malignancies, among which there were 672 with primary liver cancer (PLC) and 131 with liver metastasis, were treated with RFA. There were 781 cases who were performed percutaneously under the guidance of ultrasound, 8 cases under CT, 9 cases with laparoscopy and 5 cases with laparotomy. And there were 117 cases who were treated by RFA combined with percutaneous ethanol injection and 108 cases by RFA combined with trans-catheter arterial chemoembolization.

RESULTSIn the treatment of all the 803 patients with liver malignancies, the mortality was 0.25%, the rate of severe complications was 0.37%. The rate of complete ablation was 92.5%, the loco-recurrence rate was 13.8% and the 1, 2, 3, 4, 5-year survivals were 95.1%, 85.6%, 75.7%, 60.7% and 47.5%, respectively. For the 672 patients with PLCs, the 1, 2, 3, 4, 5-year survivals with stage Ia (Chinese staging system) were 97.8%, 91.5%, 84.6%, 77.1% and 61.9%, respectively, with stage Ib were 93.9%, 83.7%, 69.8%, 45.1% and 42.2%, respectively, with stage II were 86.2%, 67.3%, 47.3%, 17.2% and 0, respectively, and the 1, 2-year survivals with stage III were 67.8% and 0, respectively (P < 0.01).

CONCLUSIONSRFA is a safe and effective method for liver malignancy, and the tumor size and stage are important prognostic factors.

Adult ; Aged ; Aged, 80 and over ; Catheter Ablation ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; mortality ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Treatment Outcome

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.