Endogenous copper is cytotoxic to a lymphoma in primary culture which requires thiols for growth

Summary With the use of bathocuproine sulfonate, a copper-specific chelator as an indicator, we have demonstrated that copper ions, present as a natural medium constituent are toxic to the growth of a lymphoma in primary culture and are principally responsible for the growth requirement of mercaptoethanol and other thiols. By chelating trace copper normally present in the medium, bathocuproine sulfonate retarded the oxidation of cysteine to poorly utilized cystine, thus permitting its direct utilization by the cells for growth.     

Mutants of Escherichia coli deficient in 4-thiouridine in which growth is insensitive to illumination at 365 nm]

Thirteen different mutants of E coli K12 selected for a reduced near ultra-violet induced growth delay have been isolated. The t-RNAs extracted from these clones have all a depressed content of 4-thiouridine. One of these mutants, called Nop has an almost negligible growth delay and completely lacks 4-thiouridine in its t-RNAs. Thus we provide genetic proofs that 4-thiouridine is the chromophore for growth delay.     

Piroxicam-induced analgesia: Evidence for a central component which is not opioid mediated

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p<0.05) and 50% (p<0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.     

Piroxicam-induced analgesia: evidence for a central component which is not opioid mediated.

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p < 0.05) and 50% (p < 0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.     

Contribution to the primary tissue culture technique. A new method for mechanical cell dispersion

Summary A new technique for preparing primary tissue cultures by mechanical cell dispersion was idealized. The time required to prepare a culture by this procedure was greatly reduced and the cultures obtained are morphologically and physiologically of better quality than that obtained by the classical methods of enzymatic cell dispersion.This work was supported by the Conselho Nacional de Pesquisas, Fundo Especial de Despesas do Instituto Butantan and DivisãoNacional do Cancer. The authors wish to thank Mrs.Sibylle Heller for the translation.     

Rat pancreatic islet cells in primary culture: occurrence of giant cells amenable to patch clamping

Summary Neonatal and adult rat pancreatic islet cells were maintained in dissociated cell culture for up to three weeks. The unexpected occurrence of giant (40–50 m) cells was noted, some of which reacted positively to an insulin antiserum, indicating the presence of insulin. The giant cells were amenable to study using the extracellular patch clamp technique, which was used to demonstrate a population of membrane channels gating outwardly directed current in these cells.     

Rat pancreatic islet cells in primary culture: occurrence of giant cells amenable to patch clamping

Neonatal and adult rat pancreatic islet cells were maintained in dissociated cell culture for up to three weeks. The unexpected occurrence of giant (40-50 micron) cells was noted, some of which reacted positively to an insulin antiserum, indicating the presence of insulin. The giant cells were amenable to study using the extracellular patch clamp technique, which was used to demonstrate a population of membrane channels gating outwardly directed current in these cells.     

Endogenous control as a possible basis for varying migratory habits in different bird populations

Summary In handraised experimental groups of 4 populations ofSylvia atricapilla, it was found that the development of migratory restlessness under constant conditions was a fairly good reflection of the different (typical, partial, and non-) migratory habits of the populations. Thus, the different migratory habits seem to be endogenously preprogrammed and genetic in origin. The results of a preliminary cross-breeding experiment are at least compatible with the assumption that partial migratory habit in the blackcap is due to polymorphism.Supported by the Deutsche Forschungsgemeinschaft; 25th paper of the warbler program of the institute.     

Influence of presensitization with allogeneic lymphoma cells on the growth and response to therapy of radiation-induced lymphomas in mice

Summary Congenic mice were sensitized with viableH-2-incompatible radiation-induced lymphomas (RIL), challenged with syngeneic RIL and treated with bis-chloroethyl-nitrosourea. Either enhancement or inhibition of RIL was found in presensitized mice, depending on the tumor-host system used.This work was supported by Progetto Finalizzato Virus, CNR (Rome, Italy), Contract No. 770025284/1152505.Acknowledgments. I wish to thank Dr J. Mayo and Mr C.R. Reeder of the Mammalian Genetics and Animal Production Section, Division of Cancer Treatment (DCT), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda (Maryland, 20014, USA) for providing the mice used in this study. I also thank Dr H.B. Wood of the Drug Synthesis and Chemistry Branch, DCT, NCI, NIH, for furnishing the BCNU used.     

Dopamine receptor 1 localizes to neuronal cilia in a dynamic process that requires the Bardet-Biedl syndrome proteins

Primary cilia are nearly ubiquitous cellular appendages that provide important sensory and signaling functions. Ciliary dysfunction underlies numerous human diseases, collectively termed ciliopathies. Primary cilia have distinct functions on different cell types and these functions are defined by the signaling proteins that localize to the ciliary membrane. Neurons throughout the mammalian brain possess primary cilia upon which certain G protein-coupled receptors localize. Yet, the precise signaling proteins present on the vast majority of neuronal cilia are unknown. Here, we report that dopamine receptor 1 (D1) localizes to cilia on mouse central neurons, thereby implicating neuronal cilia in dopamine signaling. Interestingly, ciliary localization of D1 is dynamic, and the receptor rapidly translocates to and from cilia in response to environmental cues. Notably, the translocation of D1 from cilia requires proteins mutated in the ciliopathy Bardet-Biedl syndrome (BBS), and we find that one of the BBS proteins, Bbs5, specifically interacts with D1.     

Yeast extract as a supplement to chemically defined medium for axenic culture ofCaenorhabditis briggsae

Zusammenfassung Es wird der Nachweis erbracht, dass Hefenextrakte die Neubildung derC. briggsae in bakterienfreien (axenischen) Kulturen fördern. Durch Zufügung dieser Extrakte in einen chemisch definierten Nährboden werden grössere Nematodenpopulationen erzielt. Die biologische Aktivität wird durch Dialyse, Ammoniumsulfatniederschlag oder durch leichtes Erwärmen verstärkt.     

Influence of presensitization with allogeneic lymphoma cells on the growth and response to therapy of radiation-induced lymphomas in mice.

Congenic mice were sensitized with viable H-2-incompatible radiation-induced lymphomas (RIL), challenged with syngeneic RIL and treated with bis-chloroethyl-nitrosourea. Either enhancement or inhibition of RIL was found in presensitized mice, depending on the tumor-host system used.     

Correlation between car ownership and leukaemia: is non-occupational exposure to benzene from petrol and motor vehicle exhaust a causative factor in leukaemia and lymphoma?

Although there is widespread agreement that many cancers have environmental causes we are often unable to see associations between specific cancers and exposure to environmental chemicals. One might also speculate that the more widespread, common-place and 'normal' a chemical exposure is perceived to be then the less likely it will be that the exposure is recognised, let alone be considered to cause cancer. Widespread contamination of air by chemicals associated with internal combustion may be an example of one such 'invisible' carcinogenic exposure. Yet evidence is available which suggests that many leukaemia and lymphoma cases, as well as other cancers, may be caused by this mundane and ubiquitous environmental contamination. The hypothesis is developed that leukaemia 'clustering' as well as national leukaemia incidence may be related to non-occupational exposure to benzene formed by petrol combustion and resulting from petrol evaporation. The possible association between exposure to fuel vapours, internal combustion products and cancer merits much closer examination than it receives at present.     

Quantitative fluorimetric assay of the effect of a mycobacterial culture filtrate on the early growth of mycobacteria in vitro

Résumé On a utilisé une technique microspectrofluorométrique quantitative afin de pouvoir déterminer la multiplication initiale d'un très faible inoculum de la souche H₃₇Rv deMycobacterium tuberculosis. Cette technique a permis de mettre en évidence l'effet fortement stimulant d'un filtrat de culture de la même souche sur la multiplication bacillaire précoce, à condition que ce filtrat soit ajouté au milieu de culture après deux jours d'incubation des mycobactéries.     

Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli

Primary cilia with a diameter of ~200 nm have been implicated in development and disease. Calcium signaling within a primary cilium has never been directly visualized and has therefore remained a speculation. Fluid-shear stress and dopamine receptor type-5 (DR5) agonist are among the few stimuli that require cilia for intracellular calcium signal transduction. However, it is not known if these stimuli initiate calcium signaling within the cilium or if the calcium signal originates in the cytoplasm. Using an integrated single-cell imaging technique, we demonstrate for the first time that calcium signaling triggered by fluid-shear stress initiates in the primary cilium and can be distinguished from the subsequent cytosolic calcium response through the ryanodine receptor. Importantly, this flow-induced calcium signaling depends on the ciliary polycystin-2 calcium channel. While DR5-specific agonist induces calcium signaling mainly in the cilioplasm via ciliary CaV1.2, thrombin specifically induces cytosolic calcium signaling through the IP₃ receptor. Furthermore, a non-specific calcium ionophore triggers both ciliary and cytosolic calcium responses. We suggest that cilia not only act as sensory organelles but also function as calcium signaling compartments. Cilium-dependent signaling can spread to the cytoplasm or be contained within the cilioplasm. Our study thus provides the first model to understand signaling within the cilioplasm of a living cell.