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1.
Perforin-dependent killing of tumor cells by Vgamma1Vdelta1-bearing T-cells   总被引:1,自引:0,他引:1  
The T-cell subset expressing Vdelta2 paired primarily with Vgamma2 comprises a majority of gammadelta T-cells in human adult peripheral blood and expands significantly during a variety of infectious diseases. In contrast, the other subset of gammadelta T-cells that express Vdelta1 is rare among circulating T-cells and its function is poorly understood. Here, we show that a Vgamma1Vdelta1(+) T-cell line, 3-D, established from human peripheral blood by immortalization with Herpesvirus saimiri was able to specifically recognize tumor cells, such as K562 cells, and release cytotoxic granules containing perforin for target cell killing. Some tumor cells, including Daudi cells that are known to be susceptible to killing by Vdelta2(+) T-cells, were resistant to 3-D killing, implicating distinct pathways for tumor cell control by Vdelta1(+) and Vdelta2(+) T-cells. The 3-D T-cell receptor (TCR):CD3 complex reconstituted in TCR-deficient Jurkat cells was capable of transmitting signals, evidenced by activation of the interleukin 2 (IL-2) gene following ligation with anti-CD3 antibody, yet the TCR-reconstituted cells failed to produce IL-2 in response to the target cells. Thus, these results raise the possibility that some Vgamma1Vdelta1(+) T-cells could potentially be stimulated and lyse tumor cells via ligation of TCR/CD3-unassociated molecules.  相似文献   
2.
The caffeine-sensitive intracellular Ca store was characterized and the mechanism of action of ryanodine in the store was studied using K-depolarized guinea-pig taenia caecum. (1) After incubation of the preparation with CaCl2 (Ca loading), caffeine was applied in Ca-deprived medium, to produce a transient contraction and to monitor the amount of the stored Ca. As duration of Ca deprivation was prolonged, the amplitude of the caffeine-induced contraction was decreased. When ryanodine was applied during Ca deprivation, the rate of the decrease was remarkably accelerated. (2) The rate of rise of the contraction induced by external Ca ((Ca)o) was slowed by preceding depletion of the stored Ca by caffeine, compared with that observed in the Ca loaded preparation. However, in the presence of ryanodine, even if stored Ca was depleted by caffeine, the rate of rise of the (Ca)o-induced contraction remained at a higher level. (3) These results suggest that ryanodine stimulates a leak of the stored Ca, and that the contraction induced by the transmembrane influxed Ca could be modulated by the amount of Ca in, or leakiness of, the caffeine-sensitive Ca store.  相似文献   
3.
Lung metastasis has a great influence on the prognosis of patients with osteosarcoma. We previously established two high-metastatic sublines, M112 and M132, from the HuO9 human osteosarcoma cell line by in vivo selection. In this study, we newly isolated a high-metastatic subline, H3, and three low-metastatic sublines, L6, L12 and L13, from HuO9 by the dilution plating method. Three high-metastatic sublines produced more than 200 metastatic nodules in the lung, while three low-metastatic sublines produced no or few nodules after injection of 2 × 106 cells into the tail vein of nude mice. There were significant differences in the motility and invasiveness between high- and low-metastatic sublines, whereas the growth rates in vitro and the tumorigenicity in vivo showed no correlation with their metastatic abilities. Early adherence to culture plates was significantly lower in two of three low-metastatic sublines, which occupied smaller surface areas on the culture plates than other sublines did. Comparison of the expression of 637 cancer-related genes by cDNA microarray revealed that seven genes were differentially expressed between high- and low-metastatic sublines. Among them, five genes (AXL, TGFA, COLL7A1, WNT5A, and MKK6) were associated with adherence, motility, and/or invasiveness. These results suggest that the differences in motility/invasiveness and adhesive abilities are key determinants of lung metastasis in osteosarcoma. This revised version was published online in July 2006 with corrections to the Cover Date.  相似文献   
4.
Relevant animal models for metastasis of osteosarcoma is needed to understand the biology and to develop the treatment modality of metastasis of human osteosarcoma. Therefore, we screened six human osteosarcoma cell lines for metastatic ability in nude mice. The HuO9 cell line was identified as being metastatic to the lung after intravenous injection. We established two sublines, HuO9-M112 and HuO9-M132, with high metastatic potential to the lung from the parental HuO9 cells by in vivo selection. There were no differences between these two sublines and the parental cells in the growth rate in vitro and the tumorigenicity after subcutaneous injection in nude mice, however, mice injected with the metastatic sublines became moribund earlier than mice injected with the parental HuO9 cells did. Thus, adriamycin (ADR) and recombinant interleukin-12 (IL-12) were administered to mice injected with the HuO9-M112 subline to suppress experimental lung metastases. Production of lung colonies was significantly suppressed and the prognoses of mice were significantly improved by both ADR and IL-12 treatments. These results indicate that both ADR and IL-12 are effective agents against pulmonary metastatic osteosarcoma, and that these sublines are useful for studies on the biological behavior and treatment of pulmonary metastatic osteosarcoma. This revised version was published online in July 2006 with corrections to the Cover Date.  相似文献   
5.
Summary The modes by which Endothelin-1 (ET) induces Ca2+-influx and the relative functional importance of the different sources of Ca2+ for ET-induced contraction were studied using fura 2-loaded and unloaded rat aortic strips. ET caused an increase in the cytosolic free Ca2+ level ([Ca2+]i) followed by a tonic contraction in Ca2+-containing solution, and produced a transient elevation of [Ca2+]i followed by a small sustained contraction in Ca2+-free medium. ET also stimulated 45Ca influx into La2+-inaccessible fraction significantly. With the same change of [Ca2+]i, ET caused a larger tension than that induced by high K. ET-induced contraction and [Ca2+]i elevation were not significantly inhibited by 0.1–0.3 M nicardipine which nearly abolished the contraction and [Ca+]i elevation produced by high K. During treatment of the strips with high K, addition of ET induced further increases in [Ca2+]i and muscle tension, and vice versa. In Ca2+-free medium, ET-induced contraction was influenced neither by ryanodine-treatment nor by high K-treatment, although the former attenuated and the latter potentiated the [Ca2+]i transient induced by ET. Further, the ET-induced sustained contraction under Ca2+-free conditions began to develop after the [Ca2+]i level returned to the baseline. Thus, it seems that the Ca2+ released from the ryanodine-sensitive and -insensitive Ca2+ stores by ET may provide only a minor or indirect contribution, if any, to the tension development. ET might cause a contraction mainly by stimulating Ca2+-influx through Ca2+ channel(s) other than voltage-dependent Ca2+ channels in character, and by increasing the sensitivity of the contractile filaments to Ca2+ or activating them Ca2+-independently.Visiting from Zun Yi Medical College, China Send offprint requests to I. Takayanagi at the above address  相似文献   
6.
To determine the natural history of cervical lesions in rheumatoid arthritis, 161 patients who had been followed for a minimum of 5 years were enrolled in this study. The average follow-up period was 10.2 years (range, 5 to 20 years). The severity of the rheumatoid arthritis was classified into three types based on the multiplicity of peripheral joint rheumatoid involvement: a least erosive subset, a more erosive subset, and a mutilating disease subset. Ninety-two patients (57%) had upper cervical involvement, which progressed in the order of anterior atlantoaxial subluxation, anterior atlantoaxial subluxation combined with vertical subluxation, and vertical subluxation alone. Subaxial subluxation was found in 18 patients (11%). In 17 of these 18 patients, upper cervical lesions were also noted. The incidence of cervical involvement in each disease subset was 39% in the least erosive group, 83% in the more erosive group, and 100% in the mutilating disease group. Fifty percent of the patients with cervical involvement had neck pain, and the remaining patients were asymptomatic. Neural involvement occurred in 10 patients. In 7 of these 10 patients, vertical subluxation of the atlas was responsible for the neural deficit. Six patients required surgical intervention because of progressive myelopathy.  相似文献   
7.
We report the case of a 52-year-old woman with hepatitis B virus (HBV) reactivation during treatment for chronic graft vs. host disease (GVHD) after peripheral bone marrow transplantation (PBSCT) to treat chronic myelocytic leukemia. She was given cyclosporine and prednisolone orally to treat chronic GVHD after PBSCT. Liver dysfunction first developed 25 months after transplantation with the appearance of hepatitis B s antigen (HBsAg), hepatitis B e antigen (HBeAg), and elevation of HBV-DNA up to 4.5 log copies/ml. Retrospective examination of her serum before PBSCT proved negative for HBsAg and HBeAg, and positive for anti-HBsAg, anti-HBeAg, anti-hepatitis B core antigen, and HBV-DNA (2.7 log copies/ml), showing that she was in a state of occult HBV infection. Nucleotide sequences of the HBV genome obtained from her serum showed no core promoter mutations at nt 1762 and 1764 and no pre-core mutation at nt 1896. Polymerase chain reaction-restriction fragment length polymorphism showed that she was infected with HBV genotype B. The administration of lamivudine, a nucleoside analog, improved her liver function and reduced HBV-DNA replication. We conclude that antiviral agents, such as lamivudine, are effective for treating hepatitis B reactivation during immunosuppressive treatment, such as for GVHD. The administration of a nucleoside analog before transplantation should also be considered in the light of HBV genotypes and mutations, even if HBsAg was negative and the viral load was low before transplantation.  相似文献   
8.
9.
We report a 22-year-old female who presented with pyrexia, pancytopenia and liver dysfunction. The patient showed mild liver dysfunction with low-grade fever and mild hepatosplenomegaly 6 years previously, and autoimmune hepatitis (AIH) was diagnosed based on the examination of the laboratory data and liver biopsy. On admission, both markers of Epstein-Barr virus (EBV) and in-situ hybridisation from a liver biopsy specimen indicated chronic active EBV infection (CAEBV). The patient was administered an immunosuppressive agent and antiviral drug added to steroid therapy, but ultimately died from liver failure and virus-associated haemophagocytosis 10 months after the definite diagnosis. Retrospective examination of the serum at the diagnosis of AIH revealed extremely high titres of antibody to EBV, and EBV-DNA was also detectable by polymerase chain reaction. These results suggest the possibility that the patient may already have suffered from CAEBV at the initial diagnosis. We presume that hepatic involvement of CAEBV should be considered as differential diagnosis in cases showing liver dysfunction with clinical and biochemical features observed in AIH.  相似文献   
10.
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