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Biomedical subjects

M Poznansky

Publications and source records attributed to M Poznansky.

4 recordsLinked to original sources

Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector.

Human immunodeficiency virus type 1 (HIV-1) proviruses containing deletions between nucleotides 301 and 319 express viral proteins but exhibit marked attenuation in the packaging of viral RNA into virions (A. Lever, H. Gottlinger, W. Haseltine, and J. Sodroski, J. Virol. 63:4085-4087, 1989; A. Aldovini and R. A. Young, J. Virol. 64:1920-1926, 1990). Here we report that such packaging-defective proviruses can provide trans-acting viral elements required for the transfer of a HIV-1 vector to Jurkat human lymphocytes. The transferred vector was unable to encode HIV-1 genes, indicating that the long terminal repeats and the immediate flanking viral sequences are sufficient for packaging, reverse transcription, and integration. The generation of replication-competent viruses in this system was reduced to undetectable levels by providing the trans-acting viral functions on two separate expression plasmids. This defective retroviral vector provides a means of efficiently introducing desired genetic elements, in the absence of HIV-1 genes, into HIV-1 target cells.

Animals

Characterization and functional studies of rheumatoid synovial mast cells. Activation by secretagogues, anti-IgE, and a histamine-releasing lymphokine.

Microscopic analysis of synovial specimens from 35 patients with rheumatoid arthritis (RA) and 7 patients with osteoarthritis revealed mast cell hyperplasia in perivascular regions, in fibrous interstitial areas, and clustered around the periphery of lymphoid aggregates. Metachromatic staining, immunofluorescence studies, and ultrastructural analysis revealed a single population of connective tissue-type mast cells with surface IgE receptors. Total extractable histamine of synovial tissue was 4.15 +/- 2.30 micrograms/gm (n = 8) for RA synovium and 0.53 +/- 0.23 microgram/gm (n = 7) for OA synovium. Mast cell secretion was assessed and specific release of histamine from RA synovial mast cells was observed following stimulation with anti-IgE (32.3%), compound 48/80 (40.1%), calcium ionophore A23187 (25.2%), and a partially purified lymphokine with histamine-releasing activity (23.9%).

Antibodies, Anti-Idiotypic

Nonelectrolyte diffusion across lipid bilayer systems.

The permeability coefficients of a homologous series of amides from formamide through valeramide have been measured in spherical bilayers prepared by the method described by Jung. They do not depend directly on the water:ether partition coefficient which increases regularly with chain length. Instead there is a minimum at acetamide. This has been ascribed to the effect of steric hindrance on diffusion within the bilayer which increases with solute molar volume. This factor is of the same magnitude, though opposite in sign to the effect of lipid solubility, thus accounting for the minimum. The resistance to passage across the interface has been compared to the resistance to diffusion within the membrane. As the solute chain length increases the interface becomes more important, until for valeramide it comprises about 90% of the total resistance. Interface resistance is also important in urea permeation, causing urea to permeate much more slowly than an amide of comparable size, after allowance is made for the difference in the water:ether partition coefficient. Amide permeation coefficients have been compared with relative liposome permeation data measured by the rate of liposome swelling. The ratios of the two measures of permeation vary between 3 and 16 for the homologous amides. The apparent enthalpy of liposome permeation has been measured and found to be in the neighborhood of 12 kcal mol-1 essentially independent of chain length. Comparison of the bilayer permeability coefficients with those of red cells shows that red cell permeation by the lipophilic solutes resembles that of the bilayers, whereas permeation by the hydrophilic solutes differs significantly.

Amides