血红素氧合酶-1在器官移植中的保护作用

血红素氧合酶(heme oxygenase,HO)是体内唯一一种催化血红素分解代谢的限速酶,他可以氧化降解血红素,将其分解为一氧化碳、自由铁和胆绿素．血红素氧合酶-1(HO-1)是唯一可以被诱导的血红素氧合酶,近年来大量的研究发现HO-1具有抗炎、抗凋亡、抗增生反应等多种保护作用．HO-1不仅可以在机体生理状态下发挥作用,更为重要的是他可以在机体非正常状态包括应激状态下被诱导,被认为是在细胞受损时维持其氧化和抗氧化动态平衡的关键因素．本文就HO-1在器官移植研究领域的细胞保护作用作如下综述．     

Phase III evaluation of doxorubicin and whole-body hyperthermia in dogs with lymphoma.

Sixty-one dogs with histologically confirmed, untreated, high-grade lymphoma were evaluated and treated with doxorubicin (DOX, 30 mg/m2) alone. Forty-seven dogs (77%) achieved a complete response. Forty-six of the 47 dogs were randomized to receive five additional treatments with doxorubicin +/- whole-body hyperthermia (WBH). Median disease-free survival for the group treated with DOX alone (n = 22) was 189 days and for the DOX plus WBH (n = 24) was 239 days (p = 0.17). After the analysis was adjusted for stratification variables (i.e. institution, weight, stage), the effect of heat on disease-free survival remained statistically insignificant (p = 0.10), but suggested a tendency towards increased disease-free survival in hyperthermic dogs. Intact male dogs had significantly shorter disease-free survival than neutered males and neutered females (178 days vs 266 days, respectively; p = 0.013). No intact females were treated. Body weight, when evaluated as a continuous variable, was found to be a negative prognostic factor (p = 0.036). Tumour volume, stage and institution were not significant. Clinical incidence of cardiac dysfunction was not increased in dogs receiving DOX and WBH; however, post-mortem histological analysis of cardiac tissue suggested that the combined therapy of DOX and WBH was associated with greater myocyte degeneration (p = 0.012) and a tendency for increased cardiac fibrosis (p = 0.08). We concluded that continued refinement of DOX-WBH protocols is warranted, and may ultimately result in significant therapeutic improvement.     

Respiratory syncytial virus infection enhances the response to laryngeal chemostimulation and inhibits arousal from sleep in young lambs*

To evaluate the effect of respiratory syncytial virus (RSV) infection on the response to laryngeal chemostimulation (LCS) with water, five lambs were inoculated with human RSV and three lambs were given control media at an age of 3-5 days. During RSV infection, LCS resulted in increased inhibition of minute ventilation and delayed recovery of regular breathing. Sleep further increased the response, and arousal was less likely to occur in active sleep. Two of the five infected lambs needed resuscitation after LCS when arousal was absent. Histological studies showed bronchiolitis and pneumonitis. Laryngeal tastebud morphology was unchanged at 8 days after inoculation. However, infected lambs had disrupted tastebuds 4-6 weeks after infection. Failure to arouse and to terminate reflex apnea may play a role in the pathogenesis of the sudden infant death syndrome associated with respiratory tract infection.     

Screening tests for blood donors presumed to have transmitted the acquired immunodeficiency syndrome

We investigated 18 sets of blood donors from 12 to 50 months after they donated blood to recipients who subsequently developed the acquired immunodeficiency syndrome (AIDS). Within each donor set, only one donor was suspected of having transmitted the disease (ie, member of an AIDS risk group). The other donors (n = 189) were not risk group members and served as controls. A number of laboratory tests distinguished suspected from nonsuspected donors, including determination of T helper/T suppressor cell ratio, antibody to hepatitis B core antigen, and immune complexes, but none of these was as sensitive and specific as tests for antibody to the human retrovirus, HTLV-III/LAV.     

Characterization of nonlymphoid cells derived from rat peripheral lymph

Mesenteric lymphadenectomy in rats is followed by union of peripheral and central lymphatics, allowing the collection of intestine-derived peripheral lymph cells via the thoracic duct for several days. These cells include a proportion of nonlymphoid cells (NLC) that show irregular and heterogeneous surface morphology including long pseudopodia and veils. They stain variably for nonspecific esterase and acid phosphatase and are ATPase-positive. Their nuclei are irregular and some contain cytoplasmic inclusions, some of which show peroxidase activity and/or contain DNA. NLC have a range of densitites generally lower than that of lymphocytes. Freshly collected NLC express the leukocyte-common antigen (defined by monoclonal antibody MRC Ox 1) and Ia antigens (I-A and I-E subregion products defined by monoclonal antibodies) but they show a relative lack of other surface markers normally found on rat B or T lymphocytes (W3/13, W3/25, MRC Ox 12 (sIg), MRC Ox 19) or rat macrophages (FcR, C’R, mannose R, W3/25). In general NLC are only weakly adherent to glass or plastic. Although a subpopulation of NLC appear to have had a phagocytic past, freshly collected NLC fail to phagocytose a variety of test particles in vitro. NLC also appear incapable of pinocytosis in vitro. This heterogeneity may represent distinct subpopulations of NLC or different stages in the development of a single cell lineage. Direct cannulation of mesenteric lacteals shows that the majority of NLC are derived from the small intestine and their precursors appear to be present both in lamina propria and Peyer's patches. Kinetic studies, following irradiation or intravenous tritiated thymidine, show that the majority of NLC turn over rapidly in the intestine with a modal time of 3-5 d. Studies with bone marrow chimeras show that they are derived from a rapidly dividing precursor present in normal bone marrow. NLC occur at very low frequencies in normal thoracic duct lymph at all times following cannulation. The evidence presented suggests that NLC closely resemble mouse lymphoid dendritic cells. This conclusion is supported by evidence already obtained showing that NLC are potent stimulators of the semi-allogeneic rat primary mixed leukocyte reaction. In addition to the ceils resembling dendritic cells rare monocytoid cells are found in thoracic duct lymph of lymphadenectomized specific pathogen-free rats. The proportion of these cells increases greatly when the animals are conventionally housed. It seems probable that the physiological function of NLC is to act as accessory cells in the lymph nodes to which they normally drain. Methods for enriching NLC and thus facilitating analysis of their functions are discussed.     

Adhesiveness of the free surface of a human endometrial monolayer for trophoblast as related to actin cytoskeleton

Adhesiveness of the apical (free) plasma membrane of uterine epithelial cells for trophoblast is essential for the process of human embryo implantation. As epithelial cells are normally repellent, i.e. apically non-adhesive, we argue that a remodelling of the epithelial organization from a polarized to a non-polarized phenotype might prepare the apical pole for cell-cell adhesion during the so-called receptive phase. To identify details of apical adhesiveness we examined human epithelial RL95-2 cells (RL cells) which, in contrast to other cell lines, allow trophoblast to adhere to their apical plasma membrane. To determine whether the cytoskeletal structure is functionally critical for adhesiveness for trophoblast, RL cells were treated with actin depolymerizing cytochalasin D, i.e. 0.4 microM for 120 min. Changes in adhesiveness for trophoblast were monitored with a centrifugal force-based adhesion assay. Moreover, ultrastructural features, organization of the actin network and expression of integrins, i.e. alpha 6, beta 1, beta 4, were studied using electron microscopy, confocal laser scanning microscopy and cell surface immunogold-labelling techniques. Changes in transmission of mechanical signals via integrins into uterine cells were examined using a magnetic drag force device, thereby monitoring intracellular calcium responses. The results suggest that adhesiveness of the free surface of RL cells for human trophoblast requires an intact but non-polarized actin cytoskeleton, apically localized integrins linked to actin, and calcium signalling originating at the free surface.      

Identification of four distinct neutralizing epitopes on bluetongue virus serotype 10 using neutralizing monoclonal antibodies and neutralization-escape variants.

Neutralizing sites on bluetongue virus serotype 10 (BTV-10) were investigated with a panel of seven neutralizing monoclonal antibodies (MAbs). Each MAb was coupled to agarose beads and tested against the other MAbs and a nonneutralizing control MAb in a competitive immueprecipitation assay. In addition, neutralization-escape viral variants of BTV-10 were identified and cloned by selecting individual plaques that formed in the presence of neutralizing MAbs. Four antigenic variants were isolated, each under the selective pressure of a different MAb. Parental BTV-10 and the four antigenic variants were compared by microneutralization assay using the MAb panel. The panel of neutralizing MAbs was subdivided into four groups on the basis of these assays, indicating that at least four distinct neutralizing epitopes exist on the BTV-10 virion. These epitopes are individually defined by representative MAbs 034, 039, 041, and 045, and the results indicate that the four epitopes are interacting sites within a single antigenic domain on BTV-10 outer capsid protein VP2. This conclusion is further supported by the fact that a double-site neutralization-escape variant designated DE34/39 (sequentially produced against MAbs 034 and 039) was not neutralized by any MAb of the panel.