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Evidence is presented that constrains the earliest part of the growth history of a polygonal fault tier. Using high resolution, 3D seismic data from the West African margin, we document the interaction between a shallow buried, wedge shaped polygonal fault tier and pockmarks located at the base of the fault tier. Strongly curved patterns of perturbed polygonal faults are mapped in the shallowest portions of a tier overlying a series of pockmark craters. These perturbed patterns differ markedly from the ‘background’ polygonal pattern developed away from areas of pockmark influence. Perturbation is attributed to local stress effects relating to residual topography of the underlying pockmarks. By analysing the thickness variations of mapped layers within the polygonally faulted tier, we demonstrate that any residual topography was most likely healed after approximately one third of the total tier thickness was deposited. Hence the nucleation of the polygonal faults into their perturbed propagation trajectories must have been established within the first 100–150 m of burial. From these observations of early nucleation in the basal third of a tier, we propose a new model of polygonal fault growth in which individual faults nucleate near the base of a tier at an early stage of burial and then propagate preferentially upwards with basal tips restricted by an underlying mechanically competent unit the base of the tier. Continued growth then shifts the locus of displacement, such that final displacement distributions are more axio-symmetrically disposed with respect to the base and top of the tier.

The interfacing of man-made electronic components with specifically-folded biomacromolecules lies central not only to the development of sensory interfaces and potential new molecular-scale devices, but also enables us to analyse processes of great biological importance in a refined and controllable manner. Recent advances in both available technology, most notably optical and scanning probes in nature, and our understanding of suitable methodologies, have led us to the point where the characteristics of single biological molecules can be interrogated with good levels of reproducibility. We review here the application of scanning probe microscopy to the analysis of and experimentation on biological redox systems. Within this paper the tunnel transport characteristics, as assayed by both scanning tunnelling microscopy (STM) and conducting probe atomic force microscopy (AFM), of single metalloproteins are discussed. In a specific case study the electron transfer characteristics of the blue copper metalloprotein, azurin, are reported. The modulation of these properties under the influence of calibratable compressional force has also been examined in some detail. Work such as this enables one to reproducibly establish the conductance, barrier height, environmental sensitivity and electromechanical properties of these molecules.

From a comparison of 121 antimicrobial agents, the usefulness of substituted quinolines, in particular halquinol, has been indicated for the control of vibriosis in marine fish. From in vitro and in vivo experiments, it was deduced that halquinol inactivated rapidly the bacterial isolates, and controlled the disease manifestation in turbot ( Scophthalmus maximus L.).

Well-defined clones of human T-lymphocytes were produced amd monoclonal T-cell cultures were maintained for long periods of time. Single T-lymphocytes were isolated with the help of a micropipette from PBL cultures prior to any cellular stimulation (MLC), collected separately at the bottom of a 200 μl tissue culture microwell under the control of stereomicroscopic observation, and cultured with irradiated lymphoid cells in the presence of TCGF. After 12 days, 20–50% of the seeded wells exhibited clones of 3 × 10 4 − 10 5 T-lymphocytes, which were transferred to largeer tissue culture wells (2 ml, LINBRO) for long-term culture. Recloning of the growing cloned cells under the same conditions as the primary culture was carried out successfully. In the preliminary cytotoxic assays performed in 11 clones (a) a marked activity directed against lectin-coated targets was observed in many clones; (b) an important NK-like activity was exhibited by the clone 45B9 (65% of the tested cells lysed K562 cell targets); (c) 3 clones did not demonstrate cytotoxic activity against either PHA-coated L-1210 cells or K562 cell targets. These results could be explained hypothetically by the difference of functional maturation of T-cells within each clone.

Human normal T cells were selected for in vittro cloning according to the expression of T4, T8 or T10 antigens on individual cells. Clones were produced from each of these cells irrespective of the antigenic phenotype of the parental cell. The cloned progeny manifested, in many cases, shifts in antigen expression. Thus, T4+T8− cells gave clones expressing predominantly T4−T8+ and vice versa. The clonal expression of T4 and T8 seemed to be mutually exclusive. Antigenic shifts were recorded also in clones derived from T4−T8−T10− cells, resulting in T10+ clones which were also either T4+ or T8+ and from T4+T8−T10+ cloned cells yielding clones of either T4+ or T8+ cells. Testing functional properties we found that NK activity was mediated not only by T10+ cells but also, in some cases, by T4+ and T8+ cells. Moreover, TCGF production, which may reflect helper activity, was mediated not only by T4+ cells. Only the cytotoxic (CTL) activity seems to be confined to the T8 phenotype. Thus, it appears that T antigens, which seemed to be molecular markers of differentiation, are not markers for terminal differentiation and do not always reflect defined functional properties. These conclusions are drawn from cloning of normal T cells which manifest properties different from those of T-cell lines or T hybridomas.

This study reports the production of clones of human killer T cells grown in the presence of TCGF4 following sensitization in MLC against (1) allogeneic cells, (2) autologous Bebv+ lymphocytes, or (3) autologous lymphoma cells. Sensitization against the tumor cells required the addition of macrophages. The expression of the cytotoxic activity of the cloned T lymphocytes required re-stimulation with the specific stimulator cells. The cytotoxic activity seemed to be MHC-restricted, since (1) cloned allosensitized CTL lysed their corresponding allogeneic targets, but did not lyse autologous Bebv+ cell or K562 cells; (2) cloned CTL sensitized against autologous Bebv+ cells lysed their autologous targets but not allogeneic Bebv+ targets or K562 cells; and (3) cloned CTL sensitized against autologous Burkitt lymphoma cells lysed their corresponding lymphoma targets or autologous Bebv+ targets but did not lyse allogeneic lymphoma cells or Bebv+ cells from the same allogeneic lymphoma cells or Bebv+ cells from the same allogeneic donors. The cloned CTL were homogeneous in expressing the OK T8 molecules and in being negative for T4, T10 or M1. At any given time, 25-45% of the cloned cells manifested lytic activity. The ultrastructural properties and cell surface OK T markers were different from those of cloned human NK cells. Emphasis is focused on the differences between the structural, functional and culture characteristics of CTL clones produced by direct isolation of MLC responder cells forming conjugates with specific target cells and those of clones from transformed T-cell lines or from T hybridomas.

A new method based on the association of single lymphocytes with appropriate allogeneic tumor target cells has been developed to determine CTL frequencies in murine alloimmune lymphoid populations. As assessed by this microassociation method, CTL frequencies in alloimmune populations generated either in vivo or in vitro are higher than those obtained previously using the conjugation method. Moreover, Con A-dependent CTL are even more numerous than directly cytotoxic effector cells, especially after in vitro immunization. Finally, direct evidence is provided that individual CTL can mediate both direct and Con A-dependent lysis.

Recent reports on the use of embolization to treat intrarenal arteriovenous fistula have suggested that there is little need for surgical reconstruction. We report the successful use of intrarenal vascular reconstruction in a patient who presented with a large intrarenal arteriovenous fistula and hypertension to emphasize the fact that there still are cases that need surgical repair.

Publisher Summary This chapter discusses the source and functional characteristics of the mitogenic factor (MF) inducing continued proliferation of human T cells. There has been considerable interest in the possibility of growing T lymphocytes for prolonged periods in vitro and in preserving their functional integrity. In an experiment described in the chapter, the production of MF from single-donor PBL stimulated with PHA was maximal at 24–48 h, and it decreased thereafter. These kinetics were different from the ones obtained for commercial CM with pooled donors, which had maximal activity after 72 h of culture. It was found that 2500 R x-irradiated PBL, subsequently stimulated with PHA, produced not only normal but also enhanced levels of MF, particularly at the later harvest times. Preliminary evidence indicated that the producer cells were indeed resistant to 2500 R and were surviving and capable of producing normal MF levels for at least 4 days. To confirm the T cell nature of the MF producer cells, PBL was pretreated with a specific rabbit anti-T cell serum raised in laboratory against CTC and with rabbit complement. Such treatment, which was followed by a readjustment of viable cells to the usual 106/ml, resulted in complete abrogation of MF production.

The cell surface antigens and specificity of cultures of human natural killer (NK) cells, propagated in the presence of interleukin 2, were analyzed at the single-cell level. With the use of a micropipette isolation procedure, clones were initiated from cells of defined phenotype. The cell surface markers on the resultant clones were not stable and often diverged from those on the cells selected for initiation. Clones manifesting NK activity had low expression of T4 and T8 and most had some expression of T10, whereas clones without detectable cytotoxic activity had a considerable proportion of cells expressing T4 and/or T8 antigens. Within a cytotoxic clone, single cells shown to have killer activity were shown to express often T10 and infrequently T8; T4 was not detected on any of the reactive cells examined. The NK, reactive cells were found to express also antibody-dependent cell-mediated cytotoxicity and lectin-dependent cell-mediated cytotoxicity (LDCC), and some of the individual NK cells were shown to have the ability to lyse more than one type of target cell. However, there appeared to be considerable heterogeneity among the cells in the clones, with only 50-60% of cells displaying lytic activity against K562 cells at a given time. In addition, one cytotoxic clone appeared to have specific immune alloreactivity as well as NK and LDCC activities. The results of this study indicated that the cell surface phenotype and specificity of cytotoxic reactivity of cultured human NK cells were heterogeneous and suggested that such heterogeneity may be due to variations in the levels of differentiation and/or activation.

The cell surface antigens and specificity of cultures of human natural killer (NK) cells, propagated in the presence of interleukin 2, were analyzed at the single-cell level. With the use of a micropipette isolation procedure, clones were initiated from cells of defined phenotype. The cell surface markers on the resultant clones were not stable and often diverged from those on the cells selected for initiation. Clones manifesting NK activity had low expression of T4 and T8 and most had some expression of T10, whereas clones without detectable cytotoxic activity had a considerable proportion of cells expressing T4 and/or T8 antigens. Within a cytotoxic clone, single cells shown to have killer activity were shown to express often T10 and infrequently T8; T4 was not detected on any of the reactive cells examined. The NK, reactive cells were found to express also antibody-dependent cell-mediated cytotoxicity and lectin-dependent cell-mediated cytotoxicity (LDCC), and some of the individual NK cells were shown to have the ability to lyse more than one type of target cell. However, there appeared to be considerable heterogeneity among the cells in the clones, with only 50-60% of cells displaying lytic activity against K562 cells at a given time. In addition, one cytotoxic clone appeared to have specific immune alloreactivity as well as NK and LDCC activities. The results of this study indicated that the cell surface phenotype and specificity of cytotoxic reactivity of cultured human NK cells were heterogeneous and suggested that such heterogeneity may be due to variations in the levels of differentiation and/or activation.