Distinct immunologic specificity of tumor regression mediated by effector cells isolated from immunized and tumor-bearing mice

Sensitized T lymphocytes can mediate potent antitumor effects when transferred to tumor-bearing animals. Employing the MCA 105 and MCA 106 sarcomas, we were able to generate antitumor effector cells by immunization of syngeneic mice with tumor cells admixed with Corynebacterium parvum. These immune splenocytes could be further sensitized and expanded in culture by the in vitro sensitization (IVS) method utilizing tumor stimulator cells and IL-2. Adoptive immunotherapy of pulmonary metastases mediated by noncultured splenocytes from immunized mice or immune IVS cells showed exquisite specificity between the two sarcomas. These results demonstrate the presence of tumor-specific antigens on MCA 105 and MCA 106 tumor cells which can serve as target molecules for immunotherapy. Recently, we have generated therapeutic T lymphocytes from mice bearing progressively growing tumors by the IVS method. However, IVS cells from tumor-bearing mice showed cross-reactivity between the MCA 105 and 106 sarcomas in adoptive immunotherapy experiments. Since these IVS cells did not affect other control tumors, the limited cross-reactivity suggests the presence of common tumor-associated antigens on MCA 105 and MCA 106 tumor cells which can also serve as the target for tumor rejection. Therefore, immune responses to progressive tumor growth and to immunization are distinct with respect to antigen recognition by T lymphocytes.     

Solution structure of the chromomycin-DNA complex

The structure of the chromomycin-DNA complex at the deoxyoctanucleotide duplex level has been determined from one- and two-dimensional proton NMR studies in Mg-containing aqueous solution. The NMR results demonstrate that the antitumor agent binds as a symmetrical dimer to the self-complementary d[T-T-G-G-C-C-A-A] duplex with retention of the 2-fold symmetry in the complex. A set of intermolecular nuclear Overhauser enhancements (NOEs) establishes that two chromomycin molecules in the dimer share the minor groove at the G-G-C-C.G-G-C-C segment in such a way that each hydrophilic edge of the chromophore is located next to the G-G.C-C half-site and each C-D-E trisaccharide chain extends toward the 3'-direction of the octanucleotide duplex. In addition, the A-B disaccharide segment and the hydrophilic side chain of the antitumor agent are directed toward the phosphate backbone. The observed changes in nucleic acid NOEs and coupling patterns on complex formation establish a transition to a wider and shallower minor groove at the central G-G-C-C.G-G-C-C segment required for accommodating the chromomycin dimer. The present demonstration that chromomycin binds as a dimer and switches the conformation of the DNA at its G.C-rich minor groove binding site provides new insights into antitumor agent design and the sequence specificity of antitumor agent-DNA recognition.     

血管平滑肌细胞的钙动力学

血管平滑肌细胞外的Ca~(2+)通过多种通道进入细胞内。Ca~(2+)通道的本质是镶嵌在膜脂质双分子层中的糖蛋白,神经介质和药物可影响Ca~(2+)通道的功能。靠近胞膜的肌质网和胞膜内侧面的高亲和性Ca~(2+)结合位点是血管平滑肌细胞内储存和释放Ca~(2+)的主要部位。胞浆[Ca~(2+)]增高后在钙调蛋白的介导下引起血管收缩。高血压等血管性疾病的发生与其平滑肌细胞的钙动力学异常有关。     

突触后细胞骨架与乙酰胆碱受体簇

乙酰胆碱受体(AChR)簇的形成在神经肌接头的生长过程中是非常关键的一步。突触后细胞骨架参与AChR簇的形成。     

Inhibited enzyme electrodes. Part 3: A sensor for low levels of H2S and HCN

It is shown that an inhibited enzyme electrode, using cytochrome oxidase, will respond to H₂S, HCN and azide ion. For all three inhibitors the kinetics of the inhibition and recovery processes have been analysed using the theoretical model presented previously (Albery et al., 1990a). Rearrangement of the differential equation describing inhibition and the development of the necessary software has enabled us to obtain values of the concentration of inhibitor in a matter of seconds after exposure of the sensor. The sensor will measure concentrations of H₂S down to 1 ppm in the gas phase and concentrations of HCN and azide ion down to 0·4 μmol dm⁻³ in the solution     

Generation of therapeutic T lymphocytes from tumor-bearing mice by in vitro sensitization. Culture requirements and characterization of immunologic specificity

We have previously established an in vitro sensitization (IVS) procedure with which lymphocytes from tumor-bearing mice could be expanded and sensitized to acquire antitumor reactivity capable of mediating the regression of established pulmonary metastases from the weakly immunogenic MCA 105 murine sarcoma. Culture conditions required for the optimal generation of therapeutic effector cells were evaluated in the current study. Generation of effector cells by IVS required stimulation by intact tumor cells. Tumor cells killed by heat or disrupted by sonication were ineffective, but the antigenicity of tumor cells was not affected by gamma-irradiation. Long term established tumor cell lines could also serve as antigenic stimulator cells albeit with lower efficiency than fresh tumor cells. IL-2 was essential for cellular proliferation during IVS. The concentration of 1000 U/ml of IL-2 also induced nonspecific lymphokine-activated killer (LAK) activity. However, cytotoxic cells were generated during IVS in response to a broad range of IL-2 concentrations. At low IL-2 concentrations (2 to 10 U/ml), IVS cells were generated which displayed little or no LAK activity, had a greater therapeutic efficacy than those generated with high concentrations of IL-2 (100 to 1000 U/ml). Despite having high LAK activity, IVS cells, from cultures where IL-2 was added 3 or more days after initiation, had no therapeutic effect. Thus, the generation of therapeutic cells occurred independently of LAK cell production. Adoptive immunotherapy with IVS cells from MCA 105 tumor-bearing mice demonstrated cross-reactivity with the immunologically distinct MCA 106 but not the nonimmunogenic MCA 102 tumor. In contrast, IVS cells from MCA 106 tumor-bearing mice exhibited specific in vivo reactivity. In vitro cytotoxicity analyses revealed that IVS cells from MCA 105 and MCA 106 tumor-bearing mice were able to lyse both MCA 105 and MCA 106 target cells, but the reactivity toward inoculating tumors was highest. Considering previous findings that the MCA 105 and MCA 106 sarcomas possessed distinct tumor-specific transplantation Ag, the cross-reactivity observed in this study suggests that the immune response during progressive tumor growth may be different from that elicited in response to active immunization.     

Applied anatomy of the anterolateral femoral flap

A study of the source of the blood supply to the anterolateral femoral flap was carried out on 42 lower limbs of adult cadavers (among them 35 cadavers with injection of red latex and 1 with india ink into the arteries and 6 vascular cast specimens), and the surface locations of the vascular pedicle were detected on 50 healthy adults. It was found that the descending branch of the lateral circumflex femoral vessel was an ideal axial vessel. There are constant perforating branches of the myocutaneous artery or cutaneous branches from the intermuscular space to the anterolateral femoral skin. The area extends about 12 x 30 cm. Within the flap, the anterior branch of the anterolateral cutaneous nerve of the high is located. This flap has been widely used for free transplantation in China since 1983 with satisfactory results.     

中国的红树林

我国红树林主要分布在热带及亚热带沿海盐滩和河川出口的冲积盐性土上,包括24个科,47种,属于东方群系。从广西钦州湾开始经北海港,沿雷州半岛的海安分为两支,一支往南经海南岛的儋县新英港,向东经琼山县的东寨港和文昌县的清澜港,沿着东海岸至崖县的三亚港,又折向北到达东方县的八所港;另一支向东北经湛江的赤坎,阳江的海陵岛,台山的上下川岛,中山的三灶岛,新会的崖门,再沿海岸往北至福建的福鼎和台湾的新竹港。根据我国红树林的主要构成种类、外貌、生境,大致可分为3大群系和10个群落。(1) 矮灌木群系——这个群系多见于纬度稍高的海滩前缘,包括海榄雌群落和桐花树群落。这些群落在演替上处于前期阶段。(2) 高大稠密灌木群系——这个群系由于气温、年降雨量的差异和土壤性质的不同,组成这个群系的种类也有不同,不过都是以红树族的种类为建群种,它包括4个群落:红树群落、红海兰群落和角果木群落,这些群落在演替上属于中期阶段。(3) 乔木群系——这个群系主要分布在海南岛东北和东部海岸,所在地一般地势较高,前缘地带每日潮涨仍有海水浸淹。后缘地带只有每月大潮时才有海水到达,土壤比较固结,它包括木榄群落、海莲和尖瓣海莲群落、海桑群落及半红树林水椰群落。这些群落在演替上是处于后期阶段。组成我国红树林的种类大多数都具有较高的经济价值,如角果木是优质单宁的原料,有些种类经过发酵处理成为高营养的饲料和肥料。此外,沿海浮游生物的产量有红树林比无红树林的地带高达7倍,因此加强对红树林的经营和保护应采取积极态度和有效措施。     

中国的红树林

我国红树林主要分布在热带及亚热带沿海盐滩和河川出口的冲积盐性土上,包括24个科,47种,属于东方群系。从广西钦州湾开始经北海港,沿雷州半岛的海安分为两支,一支往南经海南岛的儋县新英港,向东经琼山县的东寨港和文昌县的清澜港,沿着东海岸至崖县的三亚港,又折向北到达东方县的八所港;另一支向东北经湛江的赤坎,阳江的海陵岛,台山的上下川岛,中山的三灶岛,新会的崖门,再沿海岸往北至福建的福鼎和台湾的新竹港。根据我国红树林的主要构成种类、外貌、生境,大致可分为3大群系和10个群落。(1) 矮灌木群系——这个群系多见于纬度稍高的海滩前缘,包括海榄雌群落和桐花树群落。这些群落在演替上处于前期阶段。(2) 高大稠密灌木群系——这个群系由于气温、年降雨量的差异和土壤性质的不同,组成这个群系的种类也有不同,不过都是以红树族的种类为建群种,它包括4个群落:红树群落、红海兰群落和角果木群落,这些群落在演替上属于中期阶段。(3) 乔木群系——这个群系主要分布在海南岛东北和东部海岸,所在地一般地势较高,前缘地带每日潮涨仍有海水浸淹。后缘地带只有每月大潮时才有海水到达,土壤比较固结,它包括木榄群落、海莲和尖瓣海莲群落、海桑群落及半红树林水椰群落。这些群落在演替上是处于后期阶段。组成我国红树林的种类大多数都具有较高的经济价值,如角果木是优质单宁的原料,有些种类经过发酵处理成为高营养的饲料和肥料。此外,沿海浮游生物的产量有红树林比无红树林的地带高达7倍,因此加强对红树林的经营和保护应采取积极态度和有效措施。