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Biomedical subjects

F Lévy

Publications and source records attributed to F Lévy.

At least 73 records · Page 4Linked to original sources

Autoradiographic detection of vasopressin binding sites, but not of oxytocin binding sites, in the sheep olfactory bulb.

Oxytocin facilitates maternal behaviour in sheep. In the present study, we searched for the presence of oxytocin and vasopressin binding sites in the sheep olfactory bulb, a brain area which is thought to be involved in specific bond formation between the ewe and its lamb. Using in vitro autoradiography, we observed binding of tritiated vasopressin to the glomerular layer of the olfactory bulb. Competition studies performed with structural analogues and the use of a 125I-labelled linear vasopressin antagonist suggested that sites which bind vasopressin are V1 type receptors. In contrast, specific binding sites for oxytocin in the olfactory bulb could be detected neither in control females, nor in ovariectomized females treated with estradiol nor in postparturient ewes, although such sites were present in the uterus.

Animals↗

Changes in the sensory processing of olfactory signals induced by birth in sheep.

After giving birth, sheep and many other species form a selective bond with their offspring based on the sense of smell. Processing of olfactory signals is altered to allow the animals to perform this selective recognition. Lamb odors have little effect on either neurotransmitter release or electrical activity of neurons in the olfactory bulb before birth. However, after birth there is an increase in the number of mitral cells, the principal cells of the olfactory bulb, that respond to lamb odors, which is associated with increased cholinergic and noradrenergic neurotransmitter release. Selective recognition of lambs is accompanied by increased activity of a subset of mitral cells and release of glutamate and gamma-aminobutyric acid (GABA) from the dendrodendritic synapses between the mitral and granule cells. The relation between the release of each transmitter after birth also suggests an increased efficacy of glutamate-evoked GABA release.

Animals↗

Intracerebral oxytocin is important for the onset of maternal behavior in inexperienced ewes delivered under peridural anesthesia.

Measurement of cerebrospinal concentrations of oxytocin (OT) in intact and peridural-anesthetized ewes showed that central release of OT during parturition is inhibited by this anesthesia. Also, observations of maternal behavior and attraction to amniotic fluid (AF) in inexperienced peridural-anesthetized parturient ewes after intracerebroventricular injections of either OT (2 x 10 micrograms) or saline showed that OT infusions increased the proportion of maternal females (2/17 vs. 10/20; p = .01) and attraction to AF. This study confirms that in sheep vaginocervical stimulation activates the oxytocinergic system, which induces the onset of maternal behavior, and that this action is not limited to maternally experienced females.

Anesthesia, Epidural↗

ATP is required for in vitro assembly of MHC class I antigens but not for transfer of peptides across the ER membrane.

We have translated the HLA-B27 heavy chain in vitro and studied its assembly with beta 2-microglobulin and peptide in microsomes from human cells. The assembly process requires ATP. However, the translocation of peptide across the endoplasmic reticulum (ER) membrane does not require ATP, and binding of biotinylated peptide to BiP, an ER luminal protein, occurs after ATP depletion. Proteinase K treatment of the microsomes does not block peptide translocation. Thus, ATP is required in the lumen of the ER for efficient assembly to occur. Microsomes prepared from Raji and T1 cells show similar levels of assembly, whereas assembly in T2 microsomes is 10-fold lower. This difference remains after peptide stimulation of assembly. The inefficient assembly in T2 microsomes is not due to impaired peptide translocation across the ER membrane, as no difference was found compared with microsomes from T1 cells. Instead, the defect seems to reside in the lumen of the ER.

Adenosine Triphosphate↗

Individual olfactory signatures as major determinants of early maternal discrimination in sheep.

Responses of recently parturient ewes to their familiar versus separated (i.e., unfamiliar) twin lambs were observed in an attempt to elucidate further the characteristics of the phenotypic traits (signatures) mediating maternal recognition and bonding. Ewes responded more positively to their familiar lamb than to its twin that had been isolated at birth. Nonetheless, those same mothers also discriminated between their separated twin and unfamiliar alien lambs. Alien lambs elicited similar rejection behavior regardless of whether they had been housed with their own mother or in isolation prior to testing. Lambs appear to have individually distinct (olfactory) signatures; however, the signatures of twin siblings may be sufficiently similar to enable the mother to detect a resemblance. No evidence suggests that acquired maternal labels play a role in either the acceptance of the ewe's own lamb(s) or rejection of aliens.

Animals↗

Importance of vaginocervical stimulation for the formation of maternal bonding in primiparous and multiparous parturient ewes.

The importance of vaginocervical stimulation for the formation of the maternal bond between a ewe and its lambs was investigated by studying the ability of artificial mechanical vaginocervical stimulation to induce adoption of an alien lamb after the selective bond with the ewe's own lambs had been formed. Results showed that for both multiparous and primiparous ewes, 5 min of mechanical VCS (using a hand) was effective in inducing complete acceptance of an alien lamb (6-48 h old) between 6.5 and 7.5 h postpartum in the majority of animals (8/10 multiparous, 8/9 primiparous) without interfering with the bond between the ewe and its own lambs. In a second group of multiparous animals, 6 out of 7 animals were also induced to completely accept an alien lamb between 26.5 and 27.5 h postpartum. It was found that the most critical aspect of the VCS was pressure on, and stretching the neck of, the cervix. Results show that VCS is not only important for the stimulation of maternal behavior, but also for the formation of the selective maternal bond. The ability of VCS to trigger the formation of a new maternal bond extends for at least 27.5 h post-partum.

Animals↗

Translocation of peptides through microsomal membranes is a rapid process and promotes assembly of HLA-B27 heavy chain and beta 2-microglobulin translated in vitro.

We have translated major histocompatibility complex (MHC) class I heavy chains and human beta 2-microglobulin in vitro in the presence of microsomal membranes and a peptide from the nucleoprotein of influenza A. This peptide stimulates assembly of HLA-B27 heavy chain and beta 2-microglobulin about fivefold. By modifying this peptide to contain biotin at its amino terminus, we could precipitate HLA-B27 heavy chains with immobilized streptavidin, thereby directly demonstrating class I heavy chain-peptide association under close to physiological conditions. The biotin-modified peptide stimulates assembly to the same extent as the unmodified peptide. Both peptides bind to the same site on the HLA-B27 molecule. Immediately after synthesis of the HLA-B27 heavy chain has been completed, it assembles with beta 2-microglobulin and peptide. These interactions occur in the lumen of the microsomes (endoplasmic reticulum), demonstrating that the peptide must cross the microsomal membrane in order to promote assembly. The transfer of peptide across the microsomal membrane is a rapid process, as peptide binding to heavy chain-beta 2-microglobulin complexes is observed in less than 1 min after addition of peptide. By using microsomes deficient of beta 2-microglobulin (from Daudi cells), we find a strict requirement of beta 2-microglobulin for detection of peptide interaction with the MHC class I heavy chain. Furthermore, we show that heavy chain interaction with beta 2-microglobulin is likely to precede peptide binding. Biotin-modified peptides are likely to become a valuable tool in studying MHC antigen interaction and assembly.

Amino Acid Sequence↗

Unscheduled DNA synthesis in rat pleural mesothelial cells treated with mineral fibres.

Unscheduled DNA synthesis (UDS) was studied in confluent rat pleural mesothelial cells (RPMCs) arrested in G0/G1 with hydroxyurea (HU) and treated with various fibre types, i.e., chrysotile, crocidolite or attapulgite. In addition, the effects of UV light and of benzo[a]pyrene were determined as references. Using autoradiography after [3H]thymidine incorporation ([3H]dThd), RPMCs treated with 4 micrograms/cm2 of chrysotile fibres exhibited a low but significant enhancement of net grains compared to untreated cells. Treatment with higher doses of chrysotile was not possible because of the impairment of microscopic observation due to the presence of the fibres. Using liquid scintillation counting, RPMCs treated with chrysotile or crocidolite showed a significant dose-dependent increase in [3H]dThd incorporation compared to untreated cells. In contrast, attapulgite did not enhance [3H]dThd incorporation compared to untreated cells. Treatment of RPMCs with 1, 2 or 4 micrograms/ml of benzo[a]pyrene resulted in a significant increase in [3H]dThd incorporation. In order to discount a possible role of S cells in the augmentation of [3H]dThd incorporation, despite the presence of 5 mM HU, S cells were counted by autoradiography. Results indicated that the percentage of S cells was similar in asbestos-treated and untreated cultures. Stimulation of the S phase also seems unlikely because treatment of RPMCs with asbestos fibres in the absence of HU resulted in a reduction of [3H]dThd incorporation attributed to an impairment of the S phase by the fibres. 1-4 micrograms/ml benzo[a]pyrene or 10-50 J/m2 UV light resulted in an approximate doubling of [3H]dThd incorporation. The effects of inhibitors of DNA repair were determined in chrysotile-treated RPMCs. [3H]dThd incorporation was inhibited by cytosine arabinoside and nalidixic acid. These results show that asbestos produces UDS in RPMCs.

Animals↗