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71.
Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.  相似文献   
72.
Direct monitoring of the free Ca2+ concentration in the sarcoplasmic reticulum (SR) was carried out in rat skeletal myotubes transfected with a specifically targeted aequorin chimera (srAEQ). Myotubes were also transfected with a chimeric aequorin (erAEQ) that we have demonstrated previously is retained in the endoplasmic reticulum (ER). Immunolocalization analysis showed that although both recombinant proteins are distributed in an endomembrane network identifiable with immature SR, the erAEQ protein was retained also in the perinuclear membrane. The difficulty of measuring [Ca2+] in 100-1000 microM range was overcome with the use of the synthetic coelenterazine analogue, coelenterazine n. We demonstrate that the steady state levels of [Ca2+] measured with srAEQ is around 300 microM, whereas that measured with erAEQ is significantly lower, i.e. around 200 microM. The effects of caffeine, high KCl, and nicotinic receptor stimulation, in the presence or absence of external calcium or after blockade of the Ca-ATPase, were investigated with both chimeras. The kinetics of [Ca2+] changes revealed by the erAEQ were similar, but not identical, neither quantitatively nor qualitatively, to those monitored with the srAEQ, indicating that at this stage of muscle development, differences exist between SR and ER in their mechanisms of Ca2+ handling. The functional implications of these findings are discussed.  相似文献   
73.
The a.c. conductivity of the proteins lysozyme and subtilisin, both in their active and inactive or inhibited forms were determined theoretically. For this, quantum mechanical calculations and a random walk theory were used. The conclusions are that these enzymatic proteins can easily transport electrons which is most probably important in their role as catalysators of biochemical reactions. The electron transport is sensitive to three-dimensional changes of the active sites of these enzymes which have more flexibility than the whole molecule. Therefore, the flexibility of the active sites of enzyme catalysts is not only important for the conformational fitting with the reactants, but also strongly influences the transport in biochemical reactions.  相似文献   
74.
Bone marrow transplantation (BMT) using HLA-partially matched family donors has produced disappointing results (25-30% of long-term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA-partially matched family donor. Both cases presented 2 first class HLA-antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine-arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine-A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long-lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA-identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA-identical donor.  相似文献   
75.
We report two cases of metastatic non-functioning pancreatic endocrine tumour with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial plasma levels of alpha-fetoprotein, initially normal, correlated well with hepatic tumour progression and were associated with fatal outcome. These results suggest that elevated plasma concentration of alpha-fetoprotein may be caused by metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial measurement may be useful in prognostic evaluation.  相似文献   
76.
Diffusion bonds have been produced between sheets of an Al-Li-Cu-Mg-Zr alloy using aluminium-4% copper vapour deposited metallic interlayers. Microstructural changes occurred both in the parent alloy and in the bond interface after diffusion bonding cycles and post-bonding heat treatments were analysed. Different metallographic techniques (light microscopy, scanning and transmission electron microscopy) have been used. Diffusion bonding trials were carried out using the same alloy (AA8090), both in non-superplastic (T6) and superplastic conditions. Differences in their behaviours in relation to diffusion bonding were observed.  相似文献   
77.
This paper concerns the plasticity constitutive laws in small strain. In the thermodynamic approach developed here, the key concept is that of internal variables. The differential nature of plasticity law has been pointed out for a long time. If we unite the invariance condition of these laws in a state variable transformation, this involves, ultimately, that the natural mathematic frame of plasticity theory is Differential Geometry. The system state is defined as a point of a differentiable manifold. The state variable are the local coordinates of this point in a chart. The internal stresses are the components of a covariant vector of the cotangent bundle to internal state manifold and the elastic domain is a convex part of cotangent vector space. The plastic yield criteria such as von Mises condition define a Riemannian structure over the manifold. The metric element is identified with the internal dissipation element. Constitutive laws link the covariant derivatives of the thermodynamic stress with the state variable. Hardening modulus splits up in two parts, kinematic hardening and metric hardening. This last is defined by Christoffel connection coefficients. Applied to von Mises isotropic yield condition, the metric hardening is identified with isotropic hardening. The Baltov-Sawczuk model is also analysed. The use of appropriate polar coordinates simplifies significantly the computations. Generalization to a significant category of non-differentiable yield criteria, such as Tresca condition, is considered by introducting a metric tensor family. The adaptation of Drucker's postulate to the proposed model requires the introduction of parallel transport of the internal stress covector. Generally, this transport is different over distinctive paths joining two points. This fact expresses internal state manifold curvature. The Riemann-Christoffel tensor is computed for von Mises, Baltov-Sawczuk and Tresca models.  相似文献   
78.
On-body communications around the human torso are considered, using ultra-wideband transmissions. The velocity of the diffracted wave propagating around the body is extracted from frequency- domain spatial correlation analyses.  相似文献   
79.
80.
A new version of the front-end application specific integrated circuit (ASIC) for co-planar-grid (CPG) sensors is presented. Compared to the first version, the ASIC is optimized for signal/noise performance, modified in peaking time, and it implements timing signals to measure the depth of interaction using the grids signals only. Experimental results using state-of the-art CPG sensors and different approaches for reducing the error due to electron trapping are reported. A new technique that makes use of the sum and difference of the grids signals is also presented.  相似文献   
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