Lead differentially modifies cytokine production in vitro and in vivo

An imbalance between helper T cell type 1 (Th1) and helper T cell type 2 (Th2) activation can result in immunodysregulations leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant humoral immunity that may culminate with an autoimmune disease. Mercury, a heavy-metal toxicant, is known to induce renal autoimmunity characterized by a predominant Th2 response. Lead, another metal toxicant, causes enhanced B cell activities and impairs host resistance to several bacterial and viral infections. In addition, Pb was reported to enhance Th2 proliferation and inhibit Th1 proliferation. The differential effects of Pb on Th subset activation have been further investigated. In vitro IL-4 production by a Th2 clone was significantly increased by the addition of PbCl2, whereas IFN gamma production by a Th1 clone was decreased by the addition of PbCl2. When BALB/c mice were subcutaneously exposed to PbCl2, ex vivo Il-4 production by anti-CD3-stimulated splenic T cells was enhanced, but IFN gamma production was inhibited. Additionally, the plasma IL-4 and IgE levels of Pb-exposed mice were increased, and the plasma IFN gamma levels were significantly lowered in the absence of any additional exogenous antigen. In vitro, ex vivo, and in vivo treatment with HgCl2 produced similar findings. This study is the first report of the preferential activation of a Th2 response by Pb in vivo and suggests that PB, like Hg, may induce autoimmune responses by upsetting the balance between Th1- and Th2-like cells, which could enhance production of antibodies to self antigens.     

Cora valveless pulsatile rotary pump: new design and control

For decades, research for developing a totally implantable artificial ventricle has been carried on. For 4 to 5 years, two devices have been investigated clinically. For many years, we have studied a rotary (but not centrifugal) pump that furnishes pulsatile flow without a valve and does not need external venting or a compliance chamber. It is a hypocycloidal pump based on the principle of the Maillard-Wankel rotary compressor. Currently made of titanium, it is activated by an electrical brushless direct-current motor. The motor-pump unit is totally sealed and implantable, without noise or vibration. This pump was implanted as a left ventricular assist device in calves. The midterm experiments showed good hemodynamic function. The hemolysis was low, but serious problems were encountered: blood components collecting on the gear mechanism inside the rotor jammed the pump. We therefore redesigned the pump to seal the gear mechanism. We used a double system to seal the open end of the rotor cavity with components polished to superfine optical quality. In addition, we developed a control system based on the study of the predicted shape of the motor current. The new design is now underway. We hope to start chronic experiments again in a few months. If the problem of sealing the bearing could be solved, the Cora ventricle could be used as permanent totally implantable left ventricular assist device.     

Simulation of leachate migration in leaky aquifers

A two-dimensional cross-section finite difference model is presented to simulate density dependent leachate migration in leaky aquifers. Unlike existing models, a new approach is adopted to couple the groundwater-flow equation and the hydrodynamic dispersion equation with the elimination of the intermediate step of calculating velocities. The concept of the reference density is employed, permitting increased accuracy (over pressure-based models) in the representation of the transport process. The model is then used to study the effect of several hydraulic and transport parameters on the flow pattern and plume migration which are found to be very sensitive to most of these parameters. Equiconcentration and equipotential lines are overlapped to provide a better understanding of the coupling effect.     

C3a is a chemotaxin for human eosinophils but not for neutrophils. I. C3a stimulation of neutrophils is secondary to eosinophil activation

Inflammatory action of the potent chemotaxin C5a has been well characterized on a variety of human cell types, including neutrophils, monocytes, basophils, and eosinophils. The cellular effects of C3a are less well defined. Contradictory reports have been published for C3a activation of neutrophils. Recent reports that C3a activates both basophils and eosinophils prompted us to reinvestigate the effects of C3a stimulation on eosinophils. We hypothesized that C3a activation of eosinophils, cells that are present in most neutrophil preparations, might lead to neutrophil activation. Using neutrophils of 98% purity, we observed no evidence of cellular activation after stimulation with either C3a, recombinant human C3a (rhC3a), or the synthetic C3a analogue C3a 57-77, Y57. Eosinophils purified to > 98% purity displayed concentration-dependent polarization, chemotaxis, and enzyme release by stimulation with C3a, rhC3a, and the synthetic C3a analogue. An inactive form of C3a, C3adesArg, failed to stimulate either eosinophils or neutrophils. Using neutrophil preparations containing 5-9% eosinophils, up to 20% of neutrophils became polarized after exposure to C3a. Likewise, we demonstrated that supernatant from C3a-stimulated eosinophils promotes neutrophil chemotaxis. Eosinophil polarization experiments were repeated in the presence of antibody to the C5a receptor (C5aR) to show that C3a and C5a interact with different receptors. C3a activates eosinophils in the presence of anti-C5aR antibody at concentrations that fully block C5a activation. We conclude that eosinophils are directly activated by either C3a or C5a, whereas C3a failed to activate neutrophils. C3a acts on eosinophils via a receptor that is distinct from C5aR. Since neutrophils are indirectly stimulated by C3a, eosinophils contaminating neutrophil preparations may explain earlier reports that C3a activates human neutrophils.     

Non-linear analysis of frames

A simple and easily programmable technique is proposed for the second-order analysis of frames. This technique involves the iterative process with modification of the stiffness matrix as well as the load vector in each iteration. Both curvature and sway effects are included. A numerical example is included to illustrate the results.     

Clinical evaluation of technetium-99m-L,L-ethylenedicysteine in patients with chronic renal failure

1. Effects of feeding condition from birth were examined on the sensitivity of neuromuscular transmission to d-tubocurarine (dTc) in vitro in male mice of the ddY strain. 2. Mice were trained to climb two separated cylindrical steel-wire tubes for feeding and drinking, respectively, from 16 days of age. Some mice were conventionally fed, from 99 days of age. Nerve-muscle preparations were made from the left phrenic nerve diaphragm muscle (DPH), the sciatic nerve soleus muscle (SOL), and the sciatic nerve extensor digitorum longus muscle (EDL) of 99-day-old and 155-day-old mice. The nerve trunk was electrically activated with trains of four pulses and tetanic pulses. 3. The sensitivity to the effects of dTc decreased in the order EDL, SOL, and DPH. This result held true in all mice tested. 4. This sensitivity was significantly potentiated by the compulsory movement. 5. The supersensitivity remained even when mice were conventionally fed after 99 days of age. 6. The compulsion rendered EDL antifatigable on tetanic stimulation. This property was also retained after a return to conventional feeding. 7. These results suggest that the effects of feeding condition from birth might remain on neuromuscular functions after termination of the conditioning.