LP-BM5 virus causes changes in lactic dehydrogenase and oxygen radical production in splenocytes of C57BL/6J mice

The LP-BM5 murine leukemia virus causes acquired immunodeficiency syndrome in C57BL/6J mice (MAIDS), similar to that of AIDS in humans. The objective of this study was to determine the effect of LP-BM5 viral infection on cellular activation and membrane integrity of splenocytes. Oxidative burst in splenocytes in response to exposure to PMA (20 microg/ml) was significantly higher (p<.02) in infected than in control mice at two weeks post-infection using luminol-enhanced chemiluminescence. By 13 weeks post-infection superoxide anion production in infected mice was significantly lower when compared to controls coinciding with decreased proliferative response to mitogens. The extent of cell membrane damage as indicated by lactic dehydrogenase (LDH) activity in serum was significantly higher in infected than in control mice (p<.001). The results from this study suggests that LP-BM5 virus causes an initial stimulation of cellular activity followed by a decreased cell activation characterized by decreased proliferation of splenocytes and decreased oxygen radical production. Decreased cell membrane integrity indicated by increased LDH activity may partly be responsible for these changes.     

NK cell proliferation and inflammation

Considerable progress has been made in recent years in understanding the biology of NK cells. NK cells are no longer 'null cells', but express an array of functionally important molecules with which they mediate and regulate their cytolytic activity and the cytokines they secrete. Activation and proliferation of NK cells in influenced by cytokines produced by activated monocytes (IL-15, IL-12, IL-10) and activated T cells (IL-2). This paper reviews the phenotype and effector functions of NK cells, their tissue distribution, and evidence that NK cells proliferate in vivo as part of productive or pathologic consequences of immunity.     

An Investigation on Noisy Environments in Evolutionary Multiobjective Optimization

In addition to satisfying several competing objectives, many real-world applications are also characterized by a certain degree of noise, manifesting itself in the form of signal distortion or uncertain information. In this paper, extensive studies are carried out to examine the impact of noisy environments in evolutionary multiobjective optimization. Three noise-handling features are then proposed based upon the analysis of empirical results, including an experiential learning directed perturbation operator that adapts the magnitude and direction of variation according to past experiences for fast convergence, a gene adaptation selection strategy that helps the evolutionary search in escaping from local optima or premature convergence, and a possibilistic archiving model based on the concept of possibility and necessity measures to deal with problem of uncertainties. In addition, the performances of various multiobjective evolutionary algorithms in noisy environments, as well as the robustness and effectiveness of the proposed features are examined based upon five benchmark problems characterized by different difficulties in local optimality, nonuniformity, discontinuity, and nonconvexity     

Pile Response Adjacent to Braced Excavation

The excavation of soil for the construction of basements or cut-and-cover tunnels results in ground movements. One particular concern is that the excavation-induced lateral soil movements may adversely affect any nearby pile foundation. The lateral loads imposed by the soil movements induce bending moments and deflections in the pile, which may lead to structural distress and failure. This paper presents the results of an actual full-scale instrumented study that was carried to examine the behavior of an existing pile due to nearby excavation activities resulting from the construction of a 16 m deep cut-and-cover tunnel. The pile was located 3 m behind a 0.8 m thick diaphragm wall. Excavation to the formation level that was 16 m below the ground surface resulted in a maximum lateral pile movement of 28 mm. A simplified numerical procedure based on the finite-element method was used to analyze the pile response. Generally, the theoretical predictions were in reasonable agreement with the measured results.     

Noninvasive evaluation of the lower extremity arterial tree and graft surveillance

The application of duplex ultrasonography in the evaluation of lower extremity arterial occlusive disease and in graft surveillance has enhanced significantly the vascular surgeon's diagnostic armamentarium. With continued refinements in gray scale image resolution, color flow, and spectral analysis, color duplex ultrasonography eventually will replace angiographic evaluation in carefully selected patients as the primary pre-interventional testing modality.     

Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.