Inhibition of rat adjuvant arthritis by a new immunosuppressive agent rubidomycin

Résumé Un nouveau composé anthracyclique à propriétés antibiotiques et cytotoxiques, la Rubidomycine (Daunomycine), a été administré à des rats peu après injection intra-dermique d'adjuvant complet de Freund. Par comparaison avec un groupe témoin qui a été traité avec un autre antibiotique, la tétracycline, non réputé cytotoxique, on a constaté une réduction marquée des lésions systémiques et de l'arthrite de la maladie provoquée par l'adjuvant.

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Work conducted during the tenure of a Nuffield Research Fellowship.

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Junior Fellow, Medical Research Council.     

Effect of nerve stimulation,denervation, and duct ligation,on kallikrein content and duct cell granules of the cat's submandibular gland

Summary Various procedures which reduce or deplete the kallikrein content of the cat's submandibular gland correspondingly reduce the number of apical granules in the striated duct cells. The kallikrein content is greatly reduced after chronic parasympathetic but not after sympathetic nerve section which suggests that the parasympathetic innervation is required for synthesis or storage of this enzyme.We wish to acknowledge the valuable assistance of Dr T. Nihei and Mr. J. Wimal in some of the enzyme measurements.This work was supported by grants from the Medical Research Council of Canada and the Alberta Heart Foundation.     

Ferromagnetism of a graphite nodule from the Canyon Diablo meteorite

There are recent reports of weak ferromagnetism in graphite and synthetic carbon materials such as rhombohedral C(60) (ref. 4), as well as a theoretical prediction of a ferromagnetic instability in graphene sheets. With very small ferromagnetic signals, it is difficult to be certain that the origin is intrinsic, rather than due to minute concentrations of iron-rich impurities. Here we take a different experimental approach to study ferromagnetism in graphitic materials, by making use of meteoritic graphite, which is strongly ferromagnetic at room temperature. We examined ten samples of extraterrestrial graphite from a nodule in the Canyon Diablo meteorite. Graphite is the major phase in every sample, but there are minor amounts of magnetite, kamacite, akaganéite, and other phases. By analysing the phase composition of a series of samples, we find that these iron-rich minerals can only account for about two-thirds of the observed magnetization. The remainder is somehow associated with graphite, corresponding to an average magnetization of 0.05 Bohr magnetons per carbon atom. The magnetic ordering temperature is near 570 K. We suggest that the ferromagnetism is a magnetic proximity effect induced at the interface with magnetite or kamacite inclusions.     

Assembly of yeast Sec proteins involved in translocation into the endoplasmic reticulum into a membrane-bound multisubunit complex

Secretory-protein translocation into the endoplasmic reticulum (ER) is thought to be catalysed by integral membrane proteins. Genetic selections uncovered three Saccharomyces cerevisiae genes (SEC61, SEC62 and SEC63), mutations in which block import of precursor proteins into the ER lumen in vivo and in vitro. The DNA sequences of SEC62 and SEC63 predict multispanning membrane proteins, and biochemical characterization of the SEC62 protein (Sec62) confirms that it is an integral ER membrane protein. Here we show that Sec61, Sec62 and Sec63 are assembled with two additional proteins into a multisubunit membrane-associated complex. These results confirm previous predictions, based upon genetic interactions between the SEC genes, that Sec61, Sec62 and Sec63 act together to facilitate protein translocation into the ER.     

Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones

Cell-cell adhesion is essential for many immunological functions, including interaction of cytotoxic T lymphocytes (CTLs) with their targets. We have explored CTL-target interactions using well-characterized cloned human CTLs. Conjugate formation between these CTLs and many antigen-negative targets is almost as efficient as with specific target cells, but does not lead to target-cell lysis. Thus, on specific target cells, adhesion by antigen-independent pathways may occur concurrently with or precede antigen recognition. The molecules LFA-1, CD2 (T11, LFA-2) and LFA-3 have been shown to be involved in human CTL conjugation with and lysis of specific target cells. Here we describe monoclonal antibody inhibition studies using individual monoclonal antibodies and mixes which demonstrate (1) that LFA-1, CD2 and LFA-3 are involved in antigen-independent conjugate formation; and (2) suggest that CD2 and LFA-3 are involved in one pathway and LFA-1 in another. We confirmed the existence of distinct pathways by the demonstration that LFA-1-dependent adhesion requires divalent cations and is temperature-sensitive whereas CD2- and LFA-3-dependent adhesion does not require divalent cations and is temperature-insensitive. Together with previous data, our studies suggest that CD2 on the effector interacts with LFA-3 as its ligand on targets.     

Fluorescence detection in automated DNA sequence analysis

We have developed a method for the partial automation of DNA sequence analysis. Fluorescence detection of the DNA fragments is accomplished by means of a fluorophore covalently attached to the oligonucleotide primer used in enzymatic DNA sequence analysis. A different coloured fluorophore is used for each of the reactions specific for the bases A, C, G and T. The reaction mixtures are combined and co-electrophoresed down a single polyacrylamide gel tube, the separated fluorescent bands of DNA are detected near the bottom of the tube, and the sequence information is acquired directly by computer.