Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects

Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.     

Oscillation of the scattering time in a 2D electron system with oval antidots

Electron scattering by a single barrier is predicted to reveal singularities as the magnetic field is changed, because the number of electron collisions with the barrier dramatically increases as chaotic orbits around the barrier are changed into periodic orbits. To test this experimentally we have measured the magnetoresistance of AlGaAs/GaAs heterostructures with a two-dimensional electron gas and a lateral lattice containing a macroscopic number of oval-shaped antidots fabricated using electron lithography. Reproducible fluctuations in the magnetoresistance are observed at low field, which are due to the oscillations of the number of electron collisions with the antidots. The number of collisions N before the electron escapes from the antidot has been calculated as a function of B in an electric field. The position of the maxima in N(B) obtained from calculations and experiment are in reasonable agreement.     

Synthesis and characterization of poly(ethylene aspartate)-metal complexes

Poly(ethylene aspartate) [PEA] was synthesized by the melt condensation of D,L-aspartic acid and ethylene glycol. PEA containing pendent amino and carbonyl groups in its repeating chain was used as the polymeric ligand for complexation with transition metal ions, viz. Co(II), Ni(II), Cu(II), Mn(II), Zn(II), Cd(II), Ca(II), Mg(II), Pb(II) and Hg(II). Complexation was found to be most effective in DMSO. The resulting polyester-metal complexes were solid coloured materials which have been characterized by IR spectroscopy, elemental analysis and magnetic susceptibility measurements. The thermal stability of the polyester-metal complexes was investigated by thermogravimetric analysis (TGA). On the basis of the physico-chemical studies, an oxygen and nitrogen coordinated structure for the polyester-metal complexes is proposed.     

ROLE OF COMPOSITION ON THE VISCOSITY AND SHEAR STRESS TEMPERATURE BEHAVIOUR OF SOME LUBE OIL BASE STOCKS

Lubricating oil base stocks differ greatly in their chemical composition and consequently in their physical properties and applications. Influence of waxes and various hydrocarbon type constituents viz saturates and aromatic components on the viscosity and shear stress as a function of temperature in different lube oil base stocks has been studied in the present paper.     

Performance analysis of an improved MMSE multiuser receiver formismatched delay channels

Motivated by the fact that time delays in a practical direct-sequence code-division multiple-access (DS-CDMA) system can never be perfectly estimated, an improved minimum-mean squared-error (MMSE)-based receiver is proposed and analyzed. Via the simple assumption of a probability distribution for the delay estimation errors, the proposed receiver can achieve a performance superior to that of the conventional MMSE (CMMSE) receiver. The performances of this improved receiver and the CMMSE receiver are compared in terms of the mean squared error (MSE), probability of error, and asymptotic multiuser efficiency (AME). As the original definition of AME does not consider mismatched channels, the behavior of three single-user receivers bearing imperfect delay estimation is also investigated. These single-user receivers are employed to define a more appropriate AME. Finally, an efficient update mechanism to accommodate dynamic channel statistics, and thus practical implementation, is proposed     

A Markovian Extension of Valiant′s Learning Model

An "Occam algorithm" learning model maintains a tentative hypothesis consistent with past observations and, when a new observation is inconsistent with the current hypothesis, updates to the next-simplest hypothesis consistent with all observations. In previous work, observations were assumed to be stochastically independent. This paper initiates study of such models under weaker Markovian assumptions on the observations, In the special case where the sequence of hypotheses satisfies a monotonicity condition, it is shown that the number of mistakes in classifying the first t observations is O(√t log 1/π_i), where π_i is the stationary probability of the initial state, i, of the Markov chain.     

Neurocontrol for lateral vehicle guidance

A solution to autonomous lateral vehicle guidance using a neurocontroller that can learn from measured human-driving data without knowledge of the physical car parameters is discussed. Simulations and practical tests confirm that a small-size feedforward autonomous neural network (21 neurons) can learn to steer a vehicle at high speeds only from looking at human-driving examples. In this way, the network learns the total closed-loop behavior, including the nonlinear dynamics of the vehicle and the driver's individual driving style. The main result of practical investigations is that the neutral controller trained on human-driving examples exhibits an aperiodic behavior that does not vanish at higher speeds (tests performed up to 130 km/h) and produces fewer lateral deviations than the linear state controller     

Portal vein replacement by hepatic vein transposition

Successful reconstruction after portal vein resection in extended liver surgery has been performed by end-to-end anastomosis, patch, or graft interposition. Previously described techniques to obtain venous grafts for portal replacement necessarily have either an additional incision or an unsuitable diameter. We developed a new method of portal vein replacement using the excised hepatic vein. This technique can be applied in major liver resections for tumors infiltrating the portal vein that have a safe distance from the hepatic vein.     

Role of nitric oxide in the regulation of the hepatic microcirculation in vivo

BACKGROUND/AIMS: Nitric oxide (NO) is an important mediator in the regulation of vascular tone. However, no data exist on the physiological role of NO in the regulation of the hepatic microcirculation. This study was designed to evaluate the role of NO in the hepatic microcirculation in vivo under physiological conditions. METHODS: The hepatic microcirculation was investigated in anesthetized rats by intravital fluorescence microscopy after injection of fluorescein-isothiocyanate-labeled erythrocytes. Following assessment of baseline sinusoidal perfusion, animals were randomly treated with L-NMMA (n=6), L-arginine (n=6), nitroprusside sodium (NPS, n=5) or a comparable volume of NaCl (n=4). Drugs were given through a portal vein catheter at three doses (Dx), each followed by intravital microscopy. L-NMMA was given: 5 mg/kg (D1), 25 mg/kg (D2), 50 mg/kg (D3); L-arginine 30 mg/kg (D1), 150 mg/kg (D2), 300 mg/kg (D3); and NPS continuously 80 microg x kg(-1) x h(-1). RESULTS: L-NMMA induced a significant increase of mean arterial blood pressure (MAP) (114 vs. 129 mm Hg; p<0.05). In contrast, MAP of NPS-treated animals decreased (107 vs. 91 mm Hg; p<0.01) whereas MAP of animals receiving L-arginine did not significantly differ. Sinusoidal blood flow revealed dose-dependent changes: L-NMMA significantly decreased perfusion of sinusoids (D1: 65%, D2: 57%, D3: 50% of baseline, p<0.05). Injection of L-arginine increased the sinusoidal flow even with the lowest dose (D1: 137%, D2: 133%, D3: 123%, p<0.05). Continuous infusion of NPS had little effect on sinusoidal blood flow at the first and second times of microscopy but sinusoidal blood flow was significantly increased at the third time (D1: 103%, D2: 106%, D3: 122%). CONCLUSIONS: Inhibition of NOS results in a dose-dependent disturbance of the hepatic microcirculation despite significantly increased MAP, whereas L-arginine increases the sinusoidal blood flow. The results indicate an important role for NO in the regulatory mechanisms of hepatic sinusoidal perfusion under physiological conditions.