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Biomedical subjects

S G Chung

Publications and source records attributed to S G Chung.

4 recordsLinked to original sources

SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2.

We have identified and characterized a potent new nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1) that also is active against HIV-2 and which interferes with virus replication by two distinct mechanisms. 1-(3-Cyclopenten-1-yl)methyl-6-(3,5-dimethylbenzoyl)-5-ethyl-2,4-pyrimidinedione (SJ-3366) inhibits HIV-1 replication at concentrations of approximately 1 nM, with a therapeutic index of greater than 4 x 10(6). The efficacy and toxicity of SJ-3366 are consistent when evaluated with established or fresh human cells, and the compound is equipotent against all strains of HIV-1 evaluated, including syncytium-inducing, non-syncytium-inducing, monocyte/macrophage-tropic, and subtype virus strains. Distinct from other members of the pharmacologic class of NNRTIs, SJ-3366 inhibited laboratory and clinical strains of HIV-2 at a concentration of approximately 150 nM, yielding a therapeutic index of approximately 20,000. Like most NNRTIs, the compound was less active when challenged with HIV-1 strains possessing the Y181C, K103N, and Y188C amino acid changes in the RT and selected for a virus with a Y181C amino acid change in the RT after five tissue culture passages in the presence of the compound. In combination anti-HIV assays with nucleoside and nonnucleoside RT and protease inhibitors, additive interactions occurred with all compounds tested with the exception of dideoxyinosine, with which a synergistic interaction was found. Biochemically, SJ-3366 exhibited a K(i) value of 3.2 nM, with a mixed mechanism of inhibition against HIV-1 RT, but it did not inhibit HIV-2 RT. SJ-3366 also inhibited the entry of both HIV-1 and HIV-2 into target cells. On the basis of its therapeutic index and multiple mechanisms of anti-HIV action, SJ-3366 represents an exciting new compound for use in HIV-infected individuals.

Drug Resistance, Microbial↗

Cytotoxic cembrenolides and steroids from the formosan soft coral Sarcophyton crassocaule.

Three new cytotoxic cembrenolide diterpenes, sarcocrassolide (1), crassolide (2), and 13-acetoxysarcocrassolide (3); a known cytotoxic cembrenolide, denticulatolide (4); and two cytotoxic steroids, (24S)-24-methylcholestane-3beta,5alpha,6beta-triol (5) and 24zeta-methylcholestane-3beta,5alpha,6beta,25-te traol-25-monoacetate (6), have been isolated from the Formosan soft coral Sarcophyton crassocaule. The structures of compounds 1-6 were determined by 1D and 2D spectral analysis.

Animals↗

Deletion of SMN and NAIP genes in Korean patients with spinal muscular atrophy.

Childhood-onset proximal spinal muscular atrophies (SMAs) are an autosomal recessive, clinically heterogeneous group of neuronopathies characterized by selective degeneration of anterior horn cells. The causative genes to be reported are survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes. The deletion of telomeric copy of SMN (SMN(T)) gene was observed in over 95% of SMAs. The deletion rate of NAIP gene is 20-50% according to disease severity. The objective of this article is to genetically characterize the childhood-onset spinal muscular atrophy in Koreans. Five Korean families (14 constituents containing 5 probands) with SMA were included in this study. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used for the deletion analysis of SMN(T). Multiplex PCR method was used for NAIP analysis. Four probands showed deletion of SMNT gene. Deletion of SMN(C) (centromeric SMN) gene was found in one proband who did not show the deletion of SMN(T) gene and in the father of one proband who showed the deletion of SMN(T) gene. The deletion of NAIP gene was not found among all the studied individuals. The extent of deletion in Koreans was smaller than that in other studied population. PCR-RFLP deletion analysis can be applied to diagnose SMA and make a prenatal diagnosis.

Adolescent↗

Optimal electrode placement in facial nerve conduction study.

This study was designed to determine the optimal sites for the active electrode in a nerve conduction study of each branch of the facial nerve. Twenty healthy male and female volunteers between 20 and 40 years old were investigated. Our criteria for the optimal site of the active electrode were initial negative deflection and maximal amplitude of the response and the most synchronized response. Optimal sites were found to be as follows: 1. Frontalis (temporal branch): a point midway between the hairline and the eyebrow along a line passing vertically through the pupil. 2. Orbicularis oculi (zygomatic branch): the medial quarter between the medial and lateral canthus. 3. Nasalis (buccal branch): muscle belly. 4. Triangularis (mandibular branch): 15 mm lateral and 25 mm below the corner of the mouth. 5. Orbicularis oris (zygomatic, mandibular and buccal branches): 2 mm below the lower lip midway between the midline and the corner of the mouth.

Adult↗