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Biomedical subjects

A T Lu

Publications and source records attributed to A T Lu.

7 recordsLinked to original sources
PubMed1998

Screening for novel antimicrobials from encoded combinatorial libraries by using a two-dimensional agar format.

A sensitive lawn-based format has been developed to screen bead-tethered combinatorial chemical libraries for antimicrobial activity. This method has been validated with beads linked to penicillin V via a photocleavable chemical linker in several analyses including a spike-and-recover experiment. The lawn-based screen sensitivity was modified to detect antibacterial compounds of modest potency, and a demonstration experiment with a naive combinatorial library of over 46,000 individual triazines was evaluated for antibacterial activity. Numerous hits were identified, and both active and inactive compounds were resynthesized and confirmed in traditional broth assays. This demonstration experiment suggests that novel antimicrobial compounds can be easily identified from very large combinatorial libraries of small, nonpeptidic compounds.

Bacillus subtilis↗
PubMed1996

Characterization of the roles of SH2 domain-containing proteins in T-lymphocyte activation by using dominant negative SH2 domains.

Activation of the T-cell antigen receptor initiates a complex signaling cascade leading to changes in cytokine gene transcription. Several proteins containing Src homology 2 (SH2) domains, capable of interacting with phosphotyrosine-containing sequences within other proteins, are involved in the activation of signaling intermediates such as p2l(ras) and phospholipase Cgamma1. In this study, we used dominant negative SH2 domains to determine the importance of SH2 domain-containing proteins for T-cell activation. We show that tandem SH2 domains of either Zap70 or Syk tyrosine kinase are potent inhibitors of signaling initiated by the T-cell receptor zeta chain in vivo while individual SH2 domains are ineffective. Thus, while only the C-terminal SH2 domains appear to have significant affinity for immunoreceptor tyrosine-based activation motifs in vitro, the N-terminal SH2 domains are necessary in vivo. We find the spacing between the tandem SH2 domains of Zap70 to be critical for in vivo interactions. The SH2 domain of the adapter protein Grb2 is an effective inhibitor in our dominant negative assay, although it has little affinity for immunoreceptor tyrosine-based activation motifs. A single point mutation that abolishes phosphotyrosine binding renders the Grb2 SH2 domain incapable of this inhibition. In contrast, the SH2 domain of Shc does not inhibit this signaling cascade. We conclude that Grb2, but not Shc, is involved in T-cell receptor signaling.

Amino Acid Sequence↗
PubMed1993

Dissolution modeling: factors affecting the dissolution rates of polydisperse powders.

The dissolution rates of two lots of hydrocortisone (fine and coarse) were simulated using a computer program based on a Noyes-Whitney-type equation. Derivations of the equation were made to compare the accuracy of simulations using spherical and cylindrical particle geometry, with and without a time-dependent diffusion layer thickness. To approximate better the shape of the hydrocortisone particles, a shape factor was used to relate cylindrical length to radius. The most accurate simulations were obtained by assuming cylindrical geometry with and without a time-dependent diffusion layer thickness for the fine and coarse hydrocortisone, respectively. The program was also modified to simulate initial particle size distributions based on the log normal probability density function.

Diffusion↗
PubMed1991

Light-directed, spatially addressable parallel chemical synthesis.

Solid-phase chemistry, photolabile protecting groups, and photolithography have been combined to achieve light-directed, spatially addressable parallel chemical synthesis to yield a highly diverse set of chemical products. Binary masking, one of many possible combinatorial synthesis strategies, yields 2n compounds in n chemical steps. An array of 1024 peptides was synthesized in ten steps, and its interaction with a monoclonal antibody was assayed by epifluorescence microscopy. High-density arrays formed by light-directed synthesis are potentially rich sources of chemical diversity for discovering new ligands that bind to biological receptors and for elucidating principles governing molecular interactions. The generality of this approach is illustrated by the light-directed synthesis of a dinucleotide. Spatially directed synthesis of complex compounds could also be used for microfabrication of devices.

Amino Acid Sequence↗
PubMed1976

Sustained downgaze deviation. Two cases without structural pretectal lesions.

Severe conjugate downward eye deviation of several days' duration in a lethargic patient with subarachnoid hemorrhage and of several weeks' duration in a comatose patient with hypoxic encephalopathy occurred in the absence of structural pretectal lesions. Persisting downgaze in a stuporous or comatose patient does not necessarily indicate anatomic pretectal damage.

Adult↗