Therapeutic and immunologic effects of iodoacetate in mature AKR mice

Résumé A des souris AKR leucémiques on administre un total de 5 injections de sulfhydryle inhibiteur, iodoacétate, à 10 jours d'intervalle. Ce régime produit une augmentation de survivance moyenne de 15 jours par rapport au groupe témoin. 40% des souris traitées vivent delà de la période d'expérimentation. Chez certaines souris traitées, on constate l'augemtation statistiquement assez importante des nombres totaux de cellules spléniques formatrices de plaquettes à tous les stades d'expérimentation.

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Supported in part by Grant No. 3362-Al from The Ohio Division of The American Cancer Society and Grant No. CA-13752-01 from The National Cancer Institute.     

An electron microscopic observation on diplococcus-shaped vesicles in papillary muscle of rat heart

Zusammenfassung Vesikelartige Gebilde wurden in Papillarmuskeln von Ratten beobachtet. Diese wie Diplokokken aussehenden Doppelvesikel lagen an der Zelloberfläche, innerhalb der transversalen Tubuli und im Zwischenraum der Glanzstreifen. Die Ergebnisse lassen eine enge Beziehung zwischen diesen diplokokkenartigen Vesikeln und den sogenannten Zystisomen vermuten.     

Regulation of lymphokine production in peripheral blood mononuclear cell cultures

Summary An increase in the production of macrophage migration inhibitory factor, chemotactic factor for neutrophils, and skin reactive factor, was observed in lymphocyte cultures if the cells were allowed to age in culture for 24 h. The increased lymphokine production was reduced by adding concanavalin A-stimulated and mitomycin C-treated suppressor cells. It is suggested that the lymphokine production could be regulated by suppressive mononuclear cells.This work was supported by the Scientific Research Council, Ministry of Health, Hungary (Code No. 421 0304011/S).     

Phospholipid alterations in liver and serum of rabbits treated with diphtheria toxin

Riassunto I fosfolipidi del siero di conigli a digiuno, trattati con tossina difterica per 15 ore, diminuiscono: questa diminuzione è a carico sorpattutto della frazione lecitinica. Le cause di questo comportamento sono brevemente discusse.

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The present research has been supported by a grant from the C.N.R. Roma (Italy).     

Stimulation of protein kinase C recruits covert calcium channels in Aplysia bag cell neurons

The modulation of voltage-activated calcium currents by protein kinases provides excitable cells with a mechanism for regulating their electrical behaviour. At the single channel level, modulation of calcium current has, to date, been characterized only in cardiac muscle, where beta-adrenergic agonists, acting through cyclic AMP-dependent protein kinase, enhance the calcium current by increasing channel availability and opening. We now report that enhancement of calcium current in the peptidergic bag cell neurons of Aplysia by protein kinase C occurs through a different mechanism, the recruitment of a previously covert class of calcium channel. Under control conditions, bag cell neurons contain only one class of voltage-activated calcium channel with a conductance of approximately 12 pS. After exposure to agents that activate protein kinase C, these neurons also express a second class of calcium channel with a different unitary conductance (approximately 24 pS) that is never seen in untreated cells.     

Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands

Tumour-associated ligands of the activating NKG2D (natural killer group 2, member D; also called KLRK1) receptor-which are induced by genotoxic or cellular stress-trigger activation of natural killer cells and co-stimulation of effector T cells, and may thus promote resistance to cancer. However, many progressing tumours in humans counter this anti-tumour activity by shedding the soluble major histocompatibility complex class-I-related ligand MICA, which induces internalization and degradation of NKG2D and stimulates population expansions of normally rare NKG2D+CD4+ T cells with negative regulatory functions. Here we show that on the surface of tumour cells, MICA associates with endoplasmic reticulum protein 5 (ERp5; also called PDIA6 or P5), which, similar to protein disulphide isomerase, usually assists in the folding of nascent proteins inside cells. Pharmacological inhibition of thioreductase activity and ERp5 gene silencing revealed that cell-surface ERp5 function is required for MICA shedding. ERp5 and membrane-anchored MICA form transitory mixed disulphide complexes from which soluble MICA is released after proteolytic cleavage near the cell membrane. Reduction of the seemingly inaccessible disulphide bond in the membrane-proximal alpha3 domain of MICA must involve a large conformational change that enables proteolytic cleavage. These results uncover a molecular mechanism whereby domain-specific deconstruction regulates MICA protein shedding, thereby promoting tumour immune evasion, and identify surface ERp5 as a strategic target for therapeutic intervention.     

Cryptomare magmatism 4.35 Gyr ago recorded in lunar meteorite Kalahari 009

The origin and evolution of the Moon remain controversial, with one of the most important questions for lunar evolution being the timing and duration of basaltic (mare) magmatism. Here we report the result of ion microprobe U-Pb dating of phosphates in a lunar meteorite, Kalahari 009, which is classified as a very-low-Ti mare-basalt breccia. In situ analyses of five phosphate grains, associated with basaltic clasts, give an age of 4.35 +/- 0.15 billion years. These ancient phosphate ages are thought to represent the crystallization ages of parental basalt magma, making Kalahari 009 one of the oldest known mare basalts. We suggest that mare basalt volcanism on the Moon started as early as 4.35 Gyr ago, relatively soon after its formation and differentiation, and preceding the bulk of lunar volcanism which ensued after the late heavy bombardment around 3.8-3.9 Gyr (refs 7 and 8). Considering the extremely low abundances of incompatible elements such as thorium and the rare earth elements in Kalahari 009 (ref. 9) and recent remote-sensing observations illustrating that the cryptomaria tend to be of very-low-Ti basalt type, we conclude that Kalahari 009 is our first sample of a very-low-Ti cryptomare from the Moon.