PubMed · 9919539
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A Hausladen, J S Stamler. 1999. Nitrosative stress.. https://doi.org/10.1016/s0076-6879(99)00143-3
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Aminoglycoside-arginine conjugates (AACs) inhibit HIV-1 replication and act as Tat antagonists. AACs compete with monoclonal antibody binding to CXCR4, compete with SDF-1alpha and HIV-1 gp120 cellular uptake, indicating that they interfere with initial steps of HIV-1 infection. We here present the selection of HIV-1 isolates resistant to hexa-arginine neomycin B conjugate (NeoR6), the most potent anti-HIV-1 AAC. We found in the NeoR6-resistant isolates the following mutations in gp120: I339T in the C3 region, S372L in the V4 region, and Q395K in the C4 region; and in gp41: S668R and F672Y in the 'heptad repeat' 2 (HR2) region. These findings strongly suggest that NeoR6 obstructs HIV-1 replication by interfering with the fusion step, dependent on both conformational changes in gp120 following CD4 and CXCR4 interaction, as well as by conformational changes in gp41 induced by HR1 and HR2 interaction. The AACs may thus represent a novel family of fusion inhibitors.
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A 6-week-old male with severe hypertension is presented. He was found to have hyperaldosteronism and a negative long polymerase chain reaction (PCR) test for glucocorticoid-remediable aldosteronism. His mother and maternal grandfather also had severe hypertension. A case is made for the possible diagnosis of familial hyperaldosteronism type II at a very early age.