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Biomedical subjects

J G Lazar

Publications and source records attributed to J G Lazar.

6 recordsLinked to original sources

Decrease of cytomegalovirus replication in human immunodeficiency virus infected-patients after treatment with highly active antiretroviral therapy.

Cytomegalovirus (CMV) viremia, as measured by a hybrid capture assay, was used to measure the effectiveness of "immune reconstitution" in human immunodeficiency virus (HIV)-infected subjects treated with highly active antiretroviral therapy (HAART). Of the 28 enrolled patients (mean age, 38 years), 86% were male and 68% were antiretrovirally naive. Of the 23 patients who returned for follow-up, baseline median characteristics were 4.1 log10 CMV DNA copies/106 white blood cells (WBCs), 5.1 log10 HIV RNA copies/mL, and 35 CD4 cells/mm3. After initiation of HAART, median log10 CMV DNA copies/106 WBCs at means of 33, 87, and 385 days were 4.0, 3.3, and 2.5, respectively. Median log10 HIV RNA levels declined from 5.1 to 1.7 at 385 days with a commensurate rise in median CD4 T cells to 166/mm3. Immune reconstitution secondary to HAART results in a significant and progressive decline in CMV viremia in the absence of specific anti-CMV therapy.

AIDS-Related Opportunistic Infections↗

Quantitation of cytomegalovirus (CMV) DNA in leukocytes of human immunodeficiency virus-infected subjects with and without CMV disease by using PCR and the SHARP Signal Detection System.

We report the development of a simple and rapid PCR assay for quantitation of the cytomegalovirus (CMV) DNA load in polymorphonuclear leukocytes. Using this system, a very good correlation was found between a high number of CMV copies in the blood and the presence of CMV disease in subjects with AIDS.

AIDS-Related Opportunistic Infections↗

Changes in mean concentration, phase shifts, and dissipation in a forced oscillatory reaction.

Experiments are presented that confirm earlier predictions that the mode of supply of reactants to a nonlinear (bio)chemical reaction determines or controls concentrations at steady states far from equilibrium. The oxidation of nicotinamide adenine dinucleotide (NADH) catalyzed by the enzyme horseradish peroxidase with continuous input of oxygen was studied; NAD+ is continuously recycled to NADH through a glucose-6-phosphate dehydrogenase system. A comparison of steady-state concentrations is made with an oscillatory oxygen input and a constant input at the same average oxygen input for both modes. By varying the frequency and amplitude of the perturbation (O2 influx), the following may be changed: the average concentration of NADH; the Gibbs free energy difference delta G of the reactants and products at steady state; the average rate of the reaction; the phase relation between the oscillatory rate and delta G; and the dissipation. These results confirm the possibility of an "alternating current chemistry," of control and optimization of thermodynamic efficiency and dissipation by means of external variation of constraints in classes of nonlinear reactions and biological pumps, and of improvements of the yield in such reactions (heterogeneous catalysis, for example).

Adenosine Triphosphate↗

Predictions of thermodynamic efficiency in a pumped biochemical reaction.

We propose and analyze a possible experimental system for the investigation of the thermodynamic efficiency of generating biochemical gradients. We investigate the efficiency of a model pump that uses 6-phosphofructokinase (EC 2.7.1.11, an enzyme that exhibits highly nonlinear kinetics), chromatophores from Rhodobacter sphaeroides, and light to generate a biochemical gradient. We analyze the experimental system and an equivalent alternative configuration and show that the establishment and maintenance of a concentration gradient across a membrane is thermodynamically equivalent to the establishment and maintenance of a stationary state in a single-phase, isothermal, open, homogeneous reaction system. With a constant input of light, the system can exist in a stable node (a stable steady state), a stable focus (upon perturbation from its steady state, the system returns to its steady state with an oscillatory component), and a stable limit cycle (at steady state the system exhibits stable oscillations). We investigate the efficiency of the system with both steady and oscillatory light input and observe efficiency changes that depend upon the autonomous state of the system and the frequency and amplitude of the periodic light input. When the system is in a stable focus, an efficiency maximum is seen when the system is perturbed at its resonant frequency. When the system is in a stable limit cycle, efficiency increases are seen near the 1:3, 1:2, and 2:1 entrainment regions and an efficiency decrease is seen near the 1:1 entrainment region. We further calculate various contributions to the efficiency: the phase shift of the force and flux, the magnitude of the response to the perturbation, and changes in the average values of the force and flux during a perturbation. We show that all three changes contribute to the overall changes in efficiency, but increases and decreases in the average force make the largest contributions.

Kinetics↗