Biomedical subjects
Publications and source records attributed to A Morel.
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Thalamocortical projections to four tonotopic fields (A, AI, P, and VP) of the cat auditory cortex were studied by using combined microelectrode mapping and retrograde axonal transport techniques. Horseradish peroxidase (HRP) or HRP combined with either tritiated bovine serum albumin or nuclear yellow was injected into identified best-frequency sites of one or two different fields in the same brain. Arrays of labeled neurons were related to thalamic nuclei defined on the basis of their cytoarchitecture and physiology. In some cases, patterns of labeling were directly compared with thalamic best-frequency maps obtained in the same brain. We compared only patterns of labeling resulting from injections into similar parts of the frequency representation in different fields to insure that observed differences in patterns of labeling did not simply reflect differences in the frequency representation at the injection sites. The thalamic projection to the four fields is divided among seven nuclei, three tonotopic nuclei (ventral nucleus, V; lateral part of the posterior group of thalamic nuclei, Po; and dorsal cap nucleus, d) and four nontonotopic nuclei (caudodorsal nucleus, cd; ventrolateral nucleus, vl; and small, Ms; and medium-large, Mg, cell regions of the medial division). Projections to each field differ, and each field receives inputs from tonotopic and nontonotopic nuclei. Field A receives its major inputs from Po and Mg, and a minor input from V. Field AI receives its major inputs from V, Po, and Mg, although Po and Mg have heavier projections to field A. Field P receives its major inputs from V, d, and vl; and minor inputs from cd, Ms, Mg, and Po. Field VP receives major inputs from V, vl, and cd; and minor inputs from d, Ms, and Mg. There are segregated territories in V and Po in which most neurons projects to one cortical field (major projection), and a smaller proportion projects to one or more other fields (minor projections). Field VP receives a major projection from the caudal pole of V. Field P receives a major projection from the caudal half of V, and from a thin band along the dorsal border of rostral V. Field AI receives a major projection from most of the rostral one-half of V, and smaller areas in Po and the caudal half of V exclusive of its caudal pole. Field A receives a major projection from most of Po.(ABSTRACT TRUNCATED AT 400 WORDS)
The selective processing activity which generates both the NH2- and COOH-terminal fragments of the octacosapeptide somatostatin-28 (S-28) was investigated. Separation into two distinct proteolytic activities was achieved by ion-exchange chromatography. An endoprotease cleaving either the substrate Pro-Arg-Glu-Arg-Lys-Ala-Gly-Ala-Lys-Asn-Tyr-NH2, i.e. [Ala17,Tyr20]S-28-(10-20)-NH2 (peptide I), or the octacosapeptide somatostatin-28, on the NH2 side of the Arg-Lys doublet was separated from an aminopeptidase B-like activity. Whereas the endoprotease cleaves a single peptide bond, between Glu12 and Arg13 of S-28, the aminopeptidase B-like enzyme removes both Arg13 and Lys14 stepwise from the NH2 terminus of the corresponding COOH-terminal fragment. This endoprotease activity peaks around pH 8.5, whereas the optimal aminopeptidase B-like activity is in the pH range 6.2-8.5. Combination of both enzymes resulted in the recovery of the overall S-28 convertase activity with an optimal pH at 7. In addition, this endoprotease appears to be very sensitive to divalent cations since it is strongly inhibited by chelating agents. The use of selectively modified undecapeptides derived from the reference substrate peptide I by a single modification of the amino acids Glu12, Arg13, and Lys14 at the cleavage locus showed that both basic residues are critically important, whereas Glu12 is not. It is proposed that S-28 processing involves a divalent cation-sensitive endoprotease that is sensitive to thiol reagents, which cleaves before the Arg-Lys doublet, which is not trypsin-like, and whose action is coupled to an aminopeptidase B-like enzyme.
In the medial geniculate body (MGB) of nitrous oxide anesthetized cats, the pars lateralis (PL) was the only nucleus to show a clear topographic arrangement of its neurons according to their characteristic frequency (CF). When compared to barbiturate anesthetized cats (Imig and Morel 1985a), the tonotopic organization in PL appeared less strict and was characterized by a significant local CF disparity. Furthermore, the degree of tonotopic organization varied along the rostrocaudal axis of the nucleus: it was lower in its caudal than in its rostral half. In the pars ovoidea, the rostral half of the pars magnocellularis (PM) and the suprageniculate nucleus, CF sequences and quantitative evaluations of the tonotopicity indicated the presence of some degree of tonotopic organization which was lower than in PL. No such organization was observed in the caudal part of PM nor in the ventrolateral nucleus, while in the dorsal nucleus, the proportion of tone-responding units was too low for a significant analysis.
Somatostatin-28 II, an octacosapeptide recently isolated from anglerfish pancreatic islets, was synthetized by the solid phase method along with its somatostatin-14 II and somatostatin-28 II-(1-12) corresponding domains. Homogeneity of the synthetic peptides was demonstrated by analytical RP-HPLC, thin layer chromatography and electrophoresis. The peptides were further characterized by amino acids analysis, fast atomic bombarding mass spectrometry and/or 252Cf plasma desorption mass spectrometry. Synthetic somatostatin-28 II and somatostatin-14 II displace equally well the potent agonist (Tyr0,D-Trp8)-somatostatin-14 from its specific binding sites on anterior pituitary cells membranes. Both peptides activate adenylate cyclase from dispersed rat anterior pituitary cells.
The octacosapeptide sequence [Tyr18] pro-ocytocin/neurophysin (1-18)NH2 [pro-OT/Np(1-18)NH2] was synthesized and used as substrate to detect endoprotease(s) possibly involved in the processing of this precursor in bovine hypothalamo-neurohypophyseal tract. An endopeptidase (58 Kda) was detected in Lysates made from highly purified neurosecretory granules. This protease which cleaves the peptide bond on the carboxyl side of the Lys-Arg doublet, and no single basic residue, generates both OT-Gly10-Lys11-Arg12+Ala13-Val-Leu-Asp-Leu-Tyr18 (NH2) from the octacosapeptide substrate. In addition, a carboxypeptidase B-like activity converting OT-Gly10-Lys11-Arg12 into OT-Gly10 was detected in the same granule Lysates. It is hypothesized that a combination of these endoprotease and carboxypeptidase B-like activities together with the amidating enzyme of secretory granules might participate in the cleavage and processing of pro-OT/Np in vivo.
The in vivo incorporation of [3H]phenylalanine into an apparent 15 kDa prosomatostatin was observed in the hypothalamus of rats injected with the labeled amino acid in the third ventricle. Precursor-product relationships were established between this newly synthesized material and both somatostatin-28 and -14.
The post-translational processing (maturation) of the precursors was studied on the model of the prosomatostatin. We have shown the presence of a single and common precursor to both somatostatin -28 and -14 in mouse hypothalamus, in contrast with the situation in the Teleostean fish, Lophius piscatorius. The search for a maturation activity was carried out using a synthetic undecapeptide substrate including in its sequence the cleavage site for somatostatin-14 release. Using this peptide, we characterized in rat brain cortex extracts a specific enzyme activity of 90 kD. This "maturase", colocalized in the neurosecretory granules with the somatostatin products, generates both the N-terminal peptide S-28, and the tetradecapeptide hormone (S-14) from the somatostatin-28, acting as a "S-28 convertase" producing free Arg and Lys residues present at the pair of basic amino acids signal. We propose a model where three peptide bonds are cleaved by this enzymatic activity. In the teleostean fish: Lophius piscatorius, two precursors coding for two different somatostatin were predicted by the determination of cDNA sequence. In this system, we observed the presence of a unique form of the tetradecapeptide hormone. We show that the final maturation product of the second precursor is a new 28 amino acid hormone called Somatostatin-28 II. Moreover, the product of this second gene after the action of the Somatostatin-28 convertase from rat brain cortex is the (Tyr7, Gly 10)S-14 derivative predicted by the clone.(ABSTRACT TRUNCATED AT 250 WORDS)
From April to July 1984, all of the strains recovered by 10 private laboratories in Upper-Normandy region (France) from urine samples from outpatients seen in office practices (public and private hospitals excluded) were preserved. A total of 829 strains were collected, identified and tested against antibiotics using disk diffusion techniques. These investigations, together with a synthesis of clinical findings, were carried out by the Laboratory of Bacteriology of the Rouen University Hospital. 78.1% of patients were females; all age groups were represented with a greater prevalence of subjects aged 26 to 35 and above 66. E. coli was the most prevalent pathogen (74.5% of all strains), followed by Proteus and Providencia (10%). E. coli was recovered in 78% of first infections against 67.7% of recurrent infections and 50% of prostatitis. More than 25% of strains were resistant to ampicillin; norfloxacin showed the best activity, with 96.5% of susceptible strains.
An Arg-Lys esteropeptidase that converts somatostatin-28 in vitro into somatostatin-14 was previously characterized in extracts of rat cerebral cortex. Both the octacosapeptide somatostatin-28 and a synthetic undecapeptide containing the sequence around the Arg-Lys site, i.e. Peptide I: Pro-Arg-Glu-Arg-Lys-Ala-Gly-Ala-Lys-Asn-125 I-Tyr (NH2), were used as substrates. We demonstrate that the converting activity is associated with neurosecretory granule fractions prepared from both cortical and hypothalamic tissue. This activity co-sediments with ghosts obtained from intact vesicles by osmotic shock. After solubilization either by mild ionic strength or sonication of vesicle membranes, the converting activity appears to possess properties indistinguishable from the convertase prepared directly from unfractionated tissue. It cleaves Peptide I to Ala-Gly-Ala-Lys-Asn-125I-Tyr (NH2) (Peptide II) and generates both the NH2- and COOH-terminal fragments of somatostatin-28, i.e. somatostatin-28 (1-12) and somatostatin-14, when the octacosapeptide is used as substrate. The selectivity appears to be strict and to depend upon the sequence around the Arg-Lys pair, as inferred from competition studies conducted with structural analogs possessing either an Arg-Lys or Arg-Arg doublet. It is concluded that this convertase could represent the enzyme system involved in the in vivo production of both the dodeca and tetradeca peptides from their common somatostatin-28 precursor.
The products generated after addition of the ARG-LYS esteropeptidase activity purified from rat brain to synthetic somatostatin-28 were analyzed using radioimmunoassay, HPLC and amino acid analysis. In addition to somatostatin-14, both free arginine and free Lysine were identified together with somatostatin-28. The dipeptide ARG-LYS was not present, which indicates that three peptide bonds were hydrolyzed in order to achieve excision of the doublet. Since it is likely that the octacosapeptide is a precursor for both somatostatin-14 and somatostatin-28, these observations add further support to the hypothesis that the convertase is also involved in the in vivo processing of endogenous somatostatin-28.
An Arg-Lys esteropeptidase which converts somatostatin-28 (S-28) into somatostatin-14 (S-14) was detected in rat brain cortical extracts using a synthetic undecapeptide substrate mimicking the octacosapeptide sequence at the restriction site. This enzyme system was unable to release either the octacosapeptide or S-14 from the 15,000 mol wt (15K) rat hypothalamic precursor. This argues in favor of sequential degradation of the precursor into S-14 via S-28 as an obligatory intermediate. Another in vivo processing system was analyzed in the anglerfish pancreatic Brockmann organs. Here, cloning of two cDNA corresponding to two mRNA species predicts two distinct somatostatins precursors, called prosomatostatins I and II (Hobart et al., Nature 288:137, 1980). While a single S-14 can be detected in extracts made from this pancreatic tissue, indistinguishable from the mammalian species, two S-28 species could be separated by HPLC. Immunochemical and biochemical evidence indicates that the second species should correspond to anglerfish S-28 (AF S-28), the product of prosomatostatin-II processing in vivo. Amino acid analysis, together with the determined complete amino acid sequence of this peptide, demonstrates that this is indeed the case and that AF S-28 contains in its C-terminal half the [Tyr7, Gly10] derivative of S-14. These observations give an example of a AF S-28 being a terminal active product of prosomatostatin processing. They suggest that this octacosapeptide, which is potent on the inhibition of growth hormone release by anterior pituitary cells, may play such a role in the gastrointestinal tract of the anglerfish. These results, while not excluding alternative routes, give support to a sequential processing of the 15 K precursor----S-28----S-14.
Responses of single units and clusters of units to tone burst stimulation were recorded at 100-micron intervals along vertical electrode penetrations through the medial geniculate bodies of eight barbiturate-anesthetized cats. Marking lesions were placed at two or three locations along most penetrations to aid in histological reconstruction of electrode tracks. Best frequencies and suprathreshold-response latencies were studied at each location along a penetration. The ventral nucleus is physiologically characterized as a region containing narrowly tuned, short-latency (less than or equal to 40 ms) responses and an orderly tonotopic organization. Best frequencies were plotted as a function of depth along single electrode penetrations, and the sequences from different locations in the ventral nucleus were compared. Two-dimensional best-frequency maps were obtained at different rostrocaudal levels. Each map was constructed from best frequencies encountered along several electrode penetrations in the same transverse plane in one brain. We divided the ventral nucleus into seven different rostrocaudal levels, each characterized by a different pattern of tonotopy. Caudolaterally, isofrequency contours parallel the ventrolateral border of the medial geniculate body. At middle levels, low- and mid-frequency contours course ventromedially from the dorsal border of the ventral nucleus toward its medial border, then turn sharply and continue ventrolaterally. Higher-frequency contours parallel this course, but consist of discontinuous dorsal and ventral segments. Rostrally, isofrequency contours are vertically oriented. A model of the three-dimensional tonotopic organization of the ventral nucleus is described that is consistent with the two-dimensional best-frequency maps obtained at different rostrocaudal levels and with locations of ventral nucleus neurons labeled by horseradish peroxidase injections into low-, mid-, and high-frequency representations in auditory cortex. The model includes a planar component and a concentric component. Within the planar component, low frequencies are represented laterally and high frequencies are represented rostromedially. Within the concentric component, low frequencies are represented in a central column that extends mediolaterally through a hole in the mid-frequency representation. The mid-frequency representation in turn is partially surrounded by the high-frequency representation. There is a continuous representation of a "single" frequency in both the planar and concentric components of the model.(ABSTRACT TRUNCATED AT 400 WORDS)
Responses of single units and clusters of units to tone-burst stimulation were recorded at 100-micron intervals along vertical electrode penetrations through the lateral part of the posterior group of thalamic nuclei (Po) in five barbiturate-anesthetized cats. Best frequencies and minimum response latencies to tone-burst stimulation were studied at each location along a penetration. Most of Po is located rostral to the medial geniculate body (MGB) and is contiguous with the ventral nucleus and medial division. Po is characterized physiologically by narrowly tuned, short-latency (less than 40 ms) responses. Considerable scatter of best frequencies occurs along electrode penetrations, although a clear tonotopic organization is apparent in the distribution of best frequencies obtained from several electrode penetrations located in the same frontal plane of an individual brain. A "single" frequency is represented as an irregularly shaped lamina. A three-dimensional "block" model of the tonotopic organization of Po is described in which the highest best frequencies are located caudally, and the lowest best frequencies are located rostrally within the nucleus. The high-frequency representation of Po is contiguous with the high-frequency representation of the ventral nucleus of the MGB. The low- and middle-frequency representations of the ventral nucleus and Po are discontinuous. The ventral nucleus and Po have similar physiological properties and together constitute the tonotopic division of the auditory thalamus in the cat. Neurons in the medial division adjacent to the medial border of Po are larger than neurons in Po, lack tonotopic organization, and respond at short latencies.
Group R streptococci have caused many cases of septicaemia and meningitis in patients handling live or slaughtered pigs which were the only known reservoir of group R streptococci. A human case, due to a wild boar, is reported here and it is therefore concluded that there exist both a domestic (pig) and a wild (wild boar) reservoir of group R streptococci.
Lumbricus terrestris (Annelid, Oligocheta) is capable of cellular- and humoral-specific reactions against natural antigens. Is this earthworm able to elaborate a response of antibody type against a synthetic hapten? L. terrestris have been immunized with conjugates made of one of two different synthetic haptens (400 mw) and a carrier protein: bovine serum albumin (BSA) or keyhole limpet haemocyanin (KLH). The presence of anti-hapten substances in coelomic fluid was tested against each iodinated hapten derivative (125I-hapten). The 125I-hapten-substance complexes were separated from the free derivatives by polyethylene glycol (PEG) 6000 precipitation or by gel filtration. The experiments showed that L. terrestris synthesized specific substances against the immunizing hapten. The importance of the response depended on the carrier protein and on the amount of introduced immunogen. A kinetic study of first and second immunization showed that these substances, elaborated in response to the immunization with the synthetic hapten, were synthesized by cells which kept the immunological memory. These data are discussed in relation to the humoral protection mechanisms already established in the invertebrates.
Ocytocin and vasopressin are two nonapeptides of the hypo thalamo-Post-hypophysary system. They are isolated and purified from dromedary post-hyphophysis, freshly collected in the meat centers of the south of Tunisia. The use of three chromatographies steps were found to be essential in obtaining high Pure hormones. These steps cousist in a sephadex G25 gel filtration and two successive High performance liquid chromatographies: H.P.L.C. The analysis of the two hormones by thin layer chromatography and Radioimmunoassays, and the identification of the amino-acid composition demonstrate that camel vasopressin is a 8 arginin vasopressin but ocytocin is identic to the other hormones isolated from different animal species.
A new somatostatin-28 has been isolated from the Teleostean fish (Lophius piscatorius) Brockmann organs. Determination of its aminoacid sequence indicates that it corresponds to an octacosapeptide containing in its C-terminal end the Tyr-7 Gly-10 derivative of somatostatin-14 I. This structure is in agreement with the one predicted by Hobart et al. (Nature (1980) 288, 137-141) from a cDNA nucleotide sequence. It demonstrates that, since the corresponding somatostatin-14 II cannot be detected in this organ, S-28 II is a terminal product of prosomatostatin II processing in anglerfish pancreatic islets.