Rhythmic neuronal activity in tissue culture

Résumé Les enregistrements électriques non-perturbants des neurones maintenus en culture, ont montré des décharges spontanées prototypes des aires du système nerveux central desquelles les groupes de cellules cultivées avaient été obtenues. Les groupes de neurones dont les enregistrements figurent ci-dessus, ont été extraits du télencéphale, mésencéphale, cervelet, et des tubercules quadrijumeaux de souris nouveau-nées. Seuls les neurones provenant du télencéphale n'ont pas produit de décharge électrique rhythmique.

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This work was supported in part by a Grant-in-Aid from Eli Lilly & Co.     

Hageman factor activation and tight junction disruption in mice challenged with attenuated endotoxin

Summary Endotoxin treated with chromium chloride is less toxic to mice than the parent molecule, but can disrupt intestinal permeability barriers and has an enhanced ability to activate Hageman factor.We wish to thank Drs M.W. Brightman and T.S. Reese from the Department of Neurocytology, National Institutes of Health for the use of their Balzers freeze-fracture instrument.     

Effect of vitamin A on tumor development in burned, unburned, and glucocorticoid-treated mice inoculated with an oncogenic virus.

High doses of vitamin A decreased the severity of tumor development in mice inoculated with a murine sarcoma virus; the same doses of vitamin A had no effect on the increased tumorigenesis seen in animals severely stressed with thermal injury or the increased tumorigenesis induced by exogenous glucocorticoid administration.     

A new peripheral monoamine oxidase inhibitor: 2,9-dimethyl-β-carbolinium iodide

Resumen Yoduro de 2, 9-dimetilo-carbolinio (DMCI) y no sus metabolitos inhibió la enzyma monoamino oxidasa y elevó¹⁴C-serotonia en el corazón e higado, pero no en el cerebro de ratas.

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This work is taken in part from the M. S. thesis presented byP. M. Gardner to the University of Texas Graduate School of Biomedical Sciences at Houston, 1971.     

Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants

The potential impact of pandemic influenza makes effective measures to limit the spread and morbidity of virus infection a public health priority. Antiviral drugs are seen as essential requirements for control of initial influenza outbreaks caused by a new virus, and in pre-pandemic plans there is a heavy reliance on drug stockpiles. The principal target for these drugs is a virus surface glycoprotein, neuraminidase, which facilitates the release of nascent virus and thus the spread of infection. Oseltamivir (Tamiflu) and zanamivir (Relenza) are two currently used neuraminidase inhibitors that were developed using knowledge of the enzyme structure. It has been proposed that the closer such inhibitors resemble the natural substrate, the less likely they are to select drug-resistant mutant viruses that retain viability. However, there have been reports of drug-resistant mutant selection in vitro and from infected humans. We report here the enzymatic properties and crystal structures of neuraminidase mutants from H5N1-infected patients that explain the molecular basis of resistance. Our results show that these mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding. Together with recent reports of the viability and pathogenesis of H5N1 (ref. 7) and H1N1 (ref. 8) viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir.