Dermenkephalin and deltorphin I reveal similarities within ligand-binding domains of mu- and delta-opioid receptors and an additional address subsite on the delta-receptor.

Dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), dermenkephalin (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) and deltorphin I (Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) are the first naturally occurring peptides highly potent for and almost specific to the mu- and delta-opioid receptors, respectively. The amino-terminal domains Tyr-D-X-Phe (where X is either Ala or Met) of these peptides behave as selective and potent mu-receptor ligands. Routing of Tyr-D-X-Phe to the delta- or the mu- receptor is associated with the presence or the absence at the C-terminus of an additional hydrophobic and negatively charged tetrapeptide by-passing the mu-addressing ability of the amino-terminal moiety. A study of 20 Tyr-D-X-Phe-Y-NH2 analogs with substitution of X and Y by neutral, hydrophobic, aromatic amino acids as well as by charged amino acid residues shows that tetrapeptides maintain high binding affinity and selectivity for the mu-opioid receptor. Although residue in position 4 serves a delta-address function, the tripeptide motif at the C-terminus of dermenkephalin and deltorphin I are critical components for high selectivity at delta-opioid receptor. Results demonstrate that mu- and delta-opioid receptors share topologically equivalent ligand-binding domains, or ligand-binding sequences similarities, that recognized Tyr-D-X-Phe as a consensus message-binding sequence. The delta-receptor additionally contains a unique address subsite at or near the conserved binding domain that accommodates the C-terminal tetrapeptide motif of dermenkephalin and deltorphin I.     

Ultrastructure of scales in a teleost (Carassius auratus L.) after use of rapid freeze-fixation and freeze-substitution

Summary New data on the ultrastructural features of the elasmoid scales ofCarassius auratus have been obtained by use of rapid freezing with subsequent freeze-substitution in anhydrous solvents. These are compared with the results obtained using conventional aqueous fixatives.The external layer of the scales is composed of randomly oriented collagen fibres. In the first stages of mineralization, mineral deposits are located in the interfibrillary substance where dense granules appear to be active sites of mineralization. Spheritic mineralization occurs in this layer.The fibrillary plate is composed of two kinds of collagen fibres. Most of them are organized in lamellae forming the plywood-like structure. They are thicker than the so-called TC fibres, which are oriented from the basal part towards the superficial layer. These TC fibres are involved in the first stages of mineral deposition in the fibrillary plate where inotropic mineralization occurs.The mineral phase is almost always located in the interfibrillary matrix in both layers of the elasmoid scale. In this respect, teleost scales differ from those described so far in other lower vertebrates.

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Resumé Des précisions concernant les aspects ultrastructuraux des dépôts minéraux dans les écailles deCarassius auratus ont été obtenues grâce à l'utilisation de la congélation ultra-rapide suivie d'une cryosubstitution en milieu anhydre. Ces données sont comparées à celles fournies par les méthodes usuelles utilisant des fixateurs aqueux.La couche externe des écailles comprend des fibres collagènes disposées sans ordre apparent. Les dépôts minéraux se produisent surtout dans la substance interfibrillaire où des granules denses semblent représenter des sites actifs au cours de la minéralisation apparentée au type sphéritique.La plaque basale comporte deux catégories de fibres collagènes. Les unes, les plus nombreuses, de plus fort diamètre, sont organisées en lamelles formant une structure en contre-plaqué; les autres appelées fibres TC, orientées de la base de l'écaille vers la zone superficielle, jouent un rôle important dans les premières phases de la minéralisation de type inotropique dans cette partie de l'écaille.Dans les deux couches de l'écaille, la phase minérale est surtout trouvée dans la substance interfibrillaire. De ce fait, les écailles élasmoides des Téleostéens peuvent être distinguées des autres écailles dermiques connues de Vertébrés inférieurs.

     

Human glioma tumour-associated antigens

Conclusion From this brief review it appears that at least three categories of human glioma-associated antigens may exist. The first seems to be restricted and common to gliomas. The second is shared between gliomas, normal adult brain, and fetal brain. The third is present on cells from adult and fetal tissue and on cells from tumours derived from the neural crest. The expression of glioma-associated antigens is highly variable from one tumour, or tumour cell line, to another, and reflects the phenotypic heterogeneity of the glioma group. Moreover, this heterogeneity has been found in different clones of individual glioma cell lines [1]. The fact that gliomas share some antigens with normal brain is of critical importance for immunodiagnosis or immunotherapy. It is evident that active immunotherapy for gliomas should be performed with cultured cells and not with tumour extracts, because such extracts may contain MBP.The exact nature of the various glioma-associated antigens remains to be clearly defined, however. They may belong to a group of surface glycoproteins such as those described by Lloyd et al. [24] for melanoma or more recently by Lubitz et al. [25] for glial cells.     

Effects of anti-embryonal carcinoma serum on aggregation and metabolic cooperation between teratocarcinoma cells

Effects of rabbit anti-embryonal carcinoma IgG on embryonal carcinoma cells and their differentiated derivatives were studied at different levels of cell-cell interaction. Fab fragments of anti-EC IgG were found to inhibit aggregation of the majority of EC cell lines. Two, however, were insensitive. Anti-EC Fab fragments act also on the transfer of metabolites between EC cells: the rescue of HPRT^? EC cells by HPRT⁺ EC cells in selective medium is abolished. These findings are correlated with the disappearance of tight and gap junctions from the surface of EC cells (Dunia et al., 1979). The presence of the surface structure involved in the action of anti-EC Fab fragments was tested by absorption experiments followed by decompaction test on PCC4 Aza R1 cells. All EC cell lines and two embryonic cell lines—a trophectodermal and an endodermal line—were found to bear material absorbing the decompacting activity. The results are discussed in terms of state of differentiation of the cell lines and of complexity of aggregation of embyronic cells.     

Non-monotonic effects of GABAergic synaptic inputs on neuronal firing

GABA is generally known as the principal inhibitory neurotransmitter in the nervous system, usually acting by hyperpolarizing membrane potential. However, GABAergic currents sometimes exhibit non-inhibitory effects, depending on the brain region, developmental stage or pathological condition. Here, we investigate the diverse effects of GABA on the firing rate of several single neuron models, using both analytical calculations and numerical simulations. We find that GABAergic synaptic conductance and output firing rate exhibit three qualitatively different regimes as a function of GABA reversal potential, E_GABA: monotonically decreasing for sufficiently low E_GABA (inhibitory), monotonically increasing for E_GABA above firing threshold (excitatory); and a non-monotonic region for intermediate values of E_GABA. In the non-monotonic regime, small GABA conductances have an excitatory effect while large GABA conductances show an inhibitory effect. We provide a phase diagram of different GABAergic effects as a function of GABA reversal potential and glutamate conductance. We find that noisy inputs increase the range of E_GABA for which the non-monotonic effect can be observed. We also construct a micro-circuit model of striatum to explain observed effects of GABAergic fast spiking interneurons on spiny projection neurons, including non-monotonicity, as well as the heterogeneity of the effects. Our work provides a mechanistic explanation of paradoxical effects of GABAergic synaptic inputs, with implications for understanding the effects of GABA in neural computation and development.     

Total Hip Arthroplasty: Direct Anterior Approach Versus Posterior Approach in the First Year of Practice

BackgroundThe direct anterior approach (DAA) for total hip arthroplasty (THA) has been popularized as a less invasive technique, however outcomes within the first year of practice after fellowship have not been investigated. The primary aim was to determine differences in complications and outcomes between DAA and posterior approach (PA) in the first year of practice. The secondary aim was to determine if there was a learning curve factor in DAA and PA after fellowship training.MethodsTHA cases performed by two surgeons during their first year of practice were reviewed. Overall, 181 THAs (91 DAA, 90 PA) in 168 patients, were performed. Intraoperative differences (blood loss, operative time), hospital stay, complications, reoperations, and revisions were compared.ResultsOverall surgical complications were similar between DAA and PA (11% vs. 9%, p=0.64), but complication profiles were different: dislocation (1% vs. 4%, p=0.17), intraoperative femoral fracture (2% vs. 1%, p=0.32), postoperative periprosthetic fractures (2% vs. 3%, p=0.64). neuropraxia (3% vs. 0%, p=0.08). There was no difference in rate of reoperation (1% vs. 3%, p=0.31). There was a difference in rate of revision at final follow-up (0% vs. 6%, p=0.02). DAA consisted of longer operative time (111 vs. 99 minutes; p<0.001), however was only significant in the first 50 cases (p<0.001), while the subsequent cases were similar (p=0.31). There was no difference in the first 50 cases compared to the subsequent cases for either approach regarding blood loss, complications, reoperations, or revisions.ConclusionDAA and PA for THA performed within the first year of practice exhibit similarly low complication rates, but complication profiles are different. In our series, PA did demonstrate a higher risk of revision at final follow-up. A learning curve is not unique to the DAA. Both DAA and PA THA exhibited a learning curve in the first 50 cases performed at the start of a surgeon’s practice. Level of Evidence: III