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Biomedical subjects

A Morel

Publications and source records attributed to A Morel.

At least 73 records · Page 4Linked to original sources
PubMed1991

Pharmacological characterization of serotonin-O-carboxymethyl-glycyl-tyrosinamide, a new selective indolic ligand for 5-hydroxytryptamine (5-HT)1B and 5-HT1D binding sites.

The affinity of a new serotonin (S) derivative, serotonin-O-carboxymethyl-glycyl-tyrosinamide (S-CM-GTNH2), for the various 5-hydroxytryptamine (5-HT)1 receptor subtypes was tested using quantitative autoradiography on rat and guinea pig brain sections. In the rat, S-CM-GTNH2 is 57 and 24 times more potent at 5-HT1B sites (IC50 = 28 nM) than at 5-HT1A (IC50 = 1600 nM) and 5-HT1C sites (IC50 = 670 nM), respectively. In the guinea pig, the affinity of S-CM-GTNH2 for 5-HT1D sites (IC50 = 67 nM) is 21 times higher than at 5-HT1A sites (IC50 = 1400 nM). S-CM-GTNH2 shows a low affinity (less than 10 microM) for 5-HT2 and 5-HT3 binding sites. This new ligand is therefore highly specific for 5-HT1B and 5-HT1D binding sites and can be used to further characterize the involvement of these subtypes in physiological studies focusing particularly on behavioral effects.

Animals↗
PubMed1991

[Synthesis and pharmacological study of radioiodinated serotonin derivative specific of 5-HT1B and 5-HT1D binding sites of the central nervous system].

We describe here the synthesis of a new serotonin conjugate, S-CM-GTNH2, and its radioiodinated derivative. Quantitative autoradiographic studies on rat and guinea pig brain sections incubated with 2 nM [3H]5-HT showed a preferential affinity of S-CM-GTNH2 for 5-HT1B and 5-HT1D sites. Autoradiograms from brain sections incubated with 0.02 nM S-CM-G[125I]TNH2 showed a heterogeneous anatomical distribution of the labelling with high densities in regions rich in 5-HT1B or 5-HT1D binding sites, and with no labelling of those rich in 5-HT1A or 5-HT1C sites. The pharmacological profiles of the binding sites corresponded to those of 5-HT1B and 5-HT1D receptor subtypes. The radioligand S-CM-G[125I]TNH2 is a good probe for the study of these sites and will be used for their subcellular localization in electron microscopy.

Animals↗
PubMed1990

Prosomatostatin II processing is initiated in the trans-Golgi network of anglerfish pancreatic cells.

Anglerfish prosomatostatin II, the precursor of somatostatin-28 II, is produced in different cells from prosomatostatin I, by a cleavage at Arg73. Antibodies were raised against the carboxy-terminal [64-72] portion of the precursor II upstream from somatostatin-28 II sequence. These antibodies recognized only this epitope when unmasked from the entire precursor, allowing the detection of the [1-72] domain which was isolated from pancreatic islets extracts. The antibodies were used to monitor the peptide bond cleavage occurring at the carboxy terminus of Arg73 to generate somatostatin-28 II. Immunocytochemistry revealed labeling both in the vesicles budding from the trans-Golgi network and in the dense core granules. Together, these data support the conclusions that i) prohormone processing is initiated in the Golgi apparatus of the pancreatic islet cells; ii) the "non-hormonal" [1-72] amino-terminal domain of the precursor may be involved in some intra and/or extra-cellular function(s).

Animals↗
PubMed1990

An immunoenzymoassay for histamine.

The clinical diagnosis of allergies needs appropriate tools for the measurement of histamine release from leukocyte suspension of affected patients. In the last few years the established fluorometric procedure has been challenged by alternatives like histamine radioimmunoassays (RIA). Although measurements of histamine with the latter methods make this procedure more accessible as a diagnostic tool, further simplifications are always welcomed. A newly developed immunoenzymoassay for histamine is described in the present work and compared to a recent radioimmunoassay. Sensitivity and specificity are shown to be comparable in both procedures.

Acetylcholinesterase↗
PubMed1990

Neuropeptides from the sinus gland of the lobster Homarus americanus: Characterization of hyperglycemic peptides.

In order to characterize hyperglycemic peptides from the sinus gland of the lobster, Homarus americanus, a bioassay was developed with juvenile H. gammarus. This assay was used for determining the hyperglycemic activity of peptides perified by reversed-phase high-performance liquid-chromatography, from acidic extracts of sinus gland. The major peptides are eluted in three sets of two peptides. Among them, two pairs show hyperglycemic activity when assayed on lobster; when assayed on crayfish, three peptides are active. The less hydrophobic pair consists of basic peptides (pI: 8.7), with a MW of 8633 Da., determined by fast-atom bombardment mass spectrometry. The most hydrophobic pair consists of acid peptides (pI: 5.0), with a MW of 8577 Da. Amino acid composition of the hyperglycemic peptides shows strong homologies within each pair.

Amino Acids↗
PubMed1990

Recognition of imidazole and histamine derivatives by monoclonal antibodies.

The different ways of raising antibodies to histamine are reviewed. High affinity monoclonal antibodies could be raised only against derivatized histamine. Succinyl glycinamide derivatization provided the basis of an efficient radioimmunoassay. In this paper the molecular pattern and the thermodynamical properties of histamine recognition were thoroughly investigated. Only the neutral form and not the cationic form of imidazole was recognized. As expected, the ligand recognition increased, with improved structural homology to the immunogen. However, a detailed analysis revealed a zwitterionic effect whenever a carboxylic group was present on the side chain of the ligand.

Animals↗
PubMed1990

Anatomical segregation of two cortical visual pathways in the macaque monkey.

A number of lines of evidence suggest that, in the macaque monkey, inferior parietal and inferotemporal cortices process different types of visual information. It has been suggested that visual information reaching these two subdivisions follows separate pathways from the striate cortex through the prestriate cortex. We examined directly this possibility by placing injections of the retrograde fluorescent tracers, fast blue and diamidino yellow, in inferior parietal and inferotemporal cortex and examining the spatial pattern of cortical areas containing labeled cells in two-dimensional reconstructions of the cortex. The results of injections in inferotemporal cortex show that TEO receives afferents from areas V2, ventral V3, V3A, central V4, V4t, and DPL in prestriate cortex and from areas IPa, PGa, and FST in the superior temporal sulcus (STS). Area TEp receives afferents only from V4 in prestriate cortex and from IPa, PGa, and FST in the anterior STS. Area TEa receives no prestriate input and is innervated by IPa, PGa, FST, and TPO in the anterior STS. The results of injections in inferior parietal cortex demonstrate that POa receives afferents from dorsal V3, V3A, peripheral V4, DPL, and PO in prestriate cortex, from MST and *VIP and from IPa, PGa, TPO, and FST in anterior STS. Area PGc (corresponding to 7a) is innervated by PO, MST, and by TPO in the anterior STS. Examination of the two-dimensional reconstructions of the pattern of labeling after combined injections of fast blue and diamidino yellow in areas POa and TEO revealed that these areas are principally innervated by different prestriate areas. Only a small region, centered on area V3A and extending into V4 and DPL, contained cells labeled by either injection as well as a small number of double-labeled cells. In contrast, areas POa and TEO receive afferents from extensive common regions in the anterior STS corresponding to areas IPa, PGa, and FST. These results directly demonstrate that visual information from the striate cortex reaches inferior parietal and inferotemporal cortices through largely separate prestriate cortical pathways. On the other hand, both parietal and inferotemporal cortices receive common inputs from extensive regions in the anterior STS which map play a role in linking the processing occurring in these two cortical subdivisions of the visual system.

Amidines↗
PubMed1989

Xenopus laevis skin Arg-Xaa-Val-Arg-Gly-endoprotease. A highly specific protease cleaving after a single arginine of a consensus sequence of peptide hormone precursors.

Comparison of the precursor sequence for several peptide hormones of Xenopus laevis skin revealed a consensus sequence around a single arginine cleavage site which is 100% conserved on four residues Arg-Xaa-Val-Arg-Gly (RXVRG). A tetradecapeptide substrate (Asp-Val-Asp-Glu-Arg-Asp-Val-Arg-Gly-Phe-Ala-Ser-Phe-Leu-NH2) was used as a probe to purify and characterize the putative processing endoprotease. A hydrophobic enzyme was purified at least 9000-fold from Xenopus skin exudate by a four-step procedure. This highly specific activity cleaves the Arg-Gly bond and has no effect on the Arg-Xaa bond. It was strongly inhibited by divalent ion chelators, moderately by phenylmethylsulfonyl fluoride, aprotinin, and 1-tosylamide-2-phenylethyl chloromethyl ketone, but was insensitive to soybean trypsin inhibitor. Tetradecapeptide derivatives selectively modified on each of the amino acids of the consensus sequence demonstrated the relevance of this conserved pattern to endoprotease action. This enzyme, which we refer to as RXVRG-endoprotease, is proposed to be involved in the post-translational processing of pro-caerulein, promagainin, pro-xenopsin, pro-glycyl-leucine amide, and pro-levitide of X. laevis skin secretory granules.

Amino Acid Sequence↗
PubMed1989

Characterization of a somatostatin-28 generating metallo-endoprotease from rat brain cytosol.

Brain cytosol contains a neutral metallo-protease of about 80,000 which cleaves a substrate containing the site at which mammalian prosomatostatin is cleaved to generate somatostatin 28 in vivo. This represents a cleavage on the carboxyl side of a single arginine residue at an Arg-Ser bond. The enzyme was unable to cleave several other substrates containing single arginine residues or two substrates containing an Arg-Lys or Lys-Arg pair. When it was incubated with anglerfish pancreatic prosomatostatin, it produced significant quantities of a peptide which co-eluted with somatostatin 28 II. Based on the ability of this enzyme to cleave small and large substrates related to somatostatin, it is a potential candidate for the enzymes which cleaves prosomatostatin in vivo.

Amino Acid Sequence↗
PubMed1989

Characterization of an endoprotease from rat small intestinal mucosal secretory granules which generates somatostatin-28 from prosomatostatin by cleavage after a single arginine residue.

We have extracted, characterized, and partially purified an enzyme from secretory granules from rat small intestinal mucosa which cleaves a synthetic prosomatostatin substrate on the carboxyl side of a single arginine residue. This substrate Leu-Gln-Arg-Ser-Ala-Asn-Ser-NH2 contains the monobasic site at which mammalian prosomatostatin is cleaved in vivo to generate somatostatin-28. This activity was released from the granules by osmotic shock followed by extraction with 500 mM KCl. The enzyme had a molecular weight of about 55,000, a pH optimum of about 7.5, and a Km for the synthetic substrate of 20 microM. It was partially inhibited by diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride, iodoacetate, soybean trypsin inhibitor, and EDTA. It was also very sensitive to aprotinin (complete inhibition at 25 micrograms/ml) but was not inhibited by bestatin, pepstatin, or p-chloromercuribenzoate. This endoprotease was unable to cleave three small trypsin and kallikrein substrates (N alpha-benzoyl-L-arginine ethyl ester, N alpha-benzoyl-DL-arginine p-nitroanilide, and N alpha-benzoyl-L-arginine 7-amido-4-methylcoumarin). It was unable to cleave either the Arg-Asp bond in CCK 12 or the Arg-Glu and Arg-Met bonds of synthetic peptides corresponding to sequences of anglerfish prosomatostatin II situated upstream from the somatostatin-28 domain. These observations together suggest that adjacent amino acids play a role in determining the conformational specificity of the monobasic cleavage. This soluble enzyme was also able to cleave three synthetic substrates containing dibasic residues (Arg-Lys or Lys-Arg) on the carboxyl side of the arginine, although it did so less rapidly than at the monobasic cleavage sites. When incubated with partially purified prosomatostatin from anglerfish pancreas, significant quantities of somatostatin-28 II were produced. All these cleavages were completely blocked by preincubation with aprotinin. Although further work is required to clarify the physiological role of this enzyme, it appears, in view of its catalytic properties, this endoprotease could be involved in the conversion of prosomatostatin to somatostatin-28 in intestine mucosal secretory cells.

Amino Acid Sequence↗
PubMed1988

Prosomatostatin processing in anglerfish brain, gut and pancreas.

The distribution of somatostatin immunoreactive forms in three tissues of the anglerfish (Lophius piscatorius L.) was analyzed by a combination of gel permeation, High Pressure Liquid Chromatography and amino acid analysis. The data indicate that prosomatostatins I and II are expressed in both neural and gastro-intestinal tissues and that their post-translational processing gives rise to somatostatin-14 I, somatostatin-28 II and to some of its hydroxylysine23-derivative, respectively. It is concluded that, in contrast to the mammals, production of two somatostatins in the Teleostean fish requires two structurally distinct precursors whose processing operates in a fixed pattern rather than in a tissue-specific manner.

Amino Acids↗
PubMed1988

Correlation between symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains.

Nasal challenges with pollen grains represent one of the techniques of provocation. However, the clinical criteria of positivity are not clearly established. Nasal challenges with increasing numbers of orchard-grass pollen grains were performed in 60 patients allergic to grass pollens and 20 normal subjects. Before any challenge, the nose was washed three times with saline and then lactose, and 50, 150, 450, 1350, and 4050 orchard-grass pollen grains were insufflated into the nostrils until a symptom score of 5 was reached. This score was mainly based on major symptoms of allergic rhinitis, for example, rhinorrhea, nasal obstruction, sneezes, and to a lesser extent, on minor symptoms, such as pruritus, conjunctivitis, and pharyngitis. Nasal secretions were obtained after each challenge by lavage. Histamine was titrated by a radioimmunoassay with a monoclonal antibody against acylated histamine. Prostaglandin D2 (PGD2) was assayed with an enzyme immunoassay with a polyclonal antibody against PGD2 methoxamine. None of the normal subjects had a symptom score greater than 2; 55/60 patients had a positive challenge. The release of PGD2 was significantly (p less than 0.001, Kruskal-Wallis test) correlated with a symptom score of 5; 74.5% of patients had a significant release of PGD2 in nasal secretions. In contrast, although 58.2% of patients had a release of histamine in nasal secretions when the challenge was positive, the correlation with symptom scores was not significant. PGD2 in nasal secretions increased 3.7-fold after a positive nasal challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Antiallergic activity of H1-receptor antagonists assessed by nasal challenge.

Most oral drugs used for the treatment of allergic rhinitis are classified as H1-receptor antagonists, and although they represent major sales throughout the world, their mechanism of action is still poorly known. In an attempt to understand better the in vivo therapeutic effects of these drugs, a double-blind, crossover study was carried out. The study compared the effects of terfenadine and loratadine, nonsedative H1-receptor antagonists, on the immediate allergic response of the upper airways to challenge with orchard-grass pollens in 14 highly allergic subjects. Increasing numbers of pollen grains were insufflated into the nostrils, and the response of the subjects was assessed by examining symptoms and measuring the release of histamine and prostaglandin D2 in nasal secretions. Each drug was administered for a week before challenge. This study demonstrated the clinical efficacy of both drugs by comparison to that of a control day, since symptoms were observed for a significantly (p = 0.014) greater number of pollen grains. Only one patient had a significant release of histamine when they were treated with loratadine versus 10 during control day (p less than 0.0023) and six when they were treated with terfenadine (p less than 0.01). Prostaglandin D2 release occurred with a higher allergen dose when patients were treated with both drugs. This study indicates that some H1 antagonists also possess antiallergic activities.

Adult↗
PubMed1988

Somatostatin-28 and pro-ocytocin/neurophysin convertases: basic pair selective endoproteases involved in pro-hormone processing in the rat brain cortex and bovine corpus luteum.

Two neuropeptide precursor processing enzyme systems were characterized in the rat brain cortex and bovine neurohypophysis and corpus luteum. The first one combines the action of a 90 kDa endoprotease which cleaves somatostatin-28 before the Arg-Lys doublet and that of an aminopeptidase B-like enzyme. The second system associates the action of a 58 kDa endoprotease cleaving pro-ocytocin/neurophysin (1-20) after the Lys-Arg dibasic moiety and a carboxypeptidase B-like activity. Both systems appear to be located in membrane-limited secretory vesicles of the producing organs, and to exhibit the properties of metallo-enzymes sensitive to divalent cation chelators. In contrast, they do not show the characteristics of serine-proteases and of trypsin-like enzymes. Studies with substrate analogs selectively modified at the basic doublet indicated that the integrity of both basic amino acids is essential but that conformational parameters, probably governed by the amino acid sequences flanking the basic doublet, play an important role. These data will be discussed in relation to a hypothesis on the predicted preferred secondary structure of these restriction loci.

Amino Acid Sequence↗
PubMed1988

Spontaneous and non-specific release of histamine and PGD2 by bronchoalveolar lavage cells from asthmatic and normal subjects: effect of nedocromil sodium.

Mast cells have been implicated in the pathogenesis of allergic asthma but their role in non-allergic asthma remains to be elucidated. The spontaneous and non-specific release of histamine by suboptimal doses of calcium ionophore A23187 was studied in bronchoalveolar lavage cells obtained from nine asthmatic and seven healthy individuals. Bronchoalveolar lavage was performed with saline, and total cells were incubated without any secretagogue (spontaneous histamine release) or after addition of 1.25, 2.5 and 5 microM of A23187 for 30 min (net maximal release). Histamine was titrated by using a very sensitive radioimmunoassay using a monoclonal antibody against acylated histamine. The spontaneous release was similar in asthmatic (20.6 +/- 8.2%) and healthy individuals (17.4 +/- 8.4%). The net maximal release of histamine was significantly greater in asthmatic patients (28.1 +/- 17.4%) than in normal subjects (10.3 +/- 8.9%). The release of histamine was significantly correlated to the release of PGD2 measured by enzyme immunoassay using a polyclonal antibody against methoxamine-PGD2 (Spearman rank test: 0.78, P less than 0.01). In eight subjects, the release of histamine by A23187 was studied in the presence of nedocromil sodium and it was observed that this drug significantly (P less than 0.05) decreased the net maximal release of histamine. This study shows that mast cells from asthmatic individuals have a greater releasability than those of normal subjects.

Adult↗
PubMed1988

Susceptibility of Mycobacterium avium complex to various two-drug combinations of antituberculosis agents.

The drug susceptibility of two untypable strains of Mycobacterium avium complex were studied in 7H10 agar plates containing ethambutol (EMB), isoniazid (INH), rifampicin (RMP), ethionamide (ETH), and streptomycin (SM) alone and in two-drug combinations. The effective dose inhibiting 75% of the mycobacterial population (ED 75) was estimated by a regression analysis on the probit transformed inhibition percentages and plotted on an isobologram for each combination. No major discrepancies were found between strains. Five combinations (RMP plus INH, RMP plus EMB, EMB plus SM, INH plus EMB, and ETH plus INH) showed synergistic effect, whereas five other combinations (ETH plus EMB, ETH plus RMP, ETH plus SM, SM plus RMP, and SM plus INH) showed antagonistic effect. These in vitro results are not in combination with the known results of treatment of the M. avium diseases. We conclude that the effect of drug combinations against M. avium may be strain dependent and that it is important to determine this effect in vitro before setting up a treatment protocol.

Aged↗
PubMed1988

[Histamine assay: use of a monoclonal antibody for radioimmunoassay and enzyme immunoassay].

The difficulty in raising highly specific and affined antibodies against histamine lies on the small size of this amine. For this purpose, we developed an original chemical derivatization (acylation) of histamine to induce required antibodies. It is then necessary to reproduce the same chemical modification in all protagonists of the immunoassay: immunogen, tracer and sample. We raised highly specific monoclonal antibodies. The acylation of histamine increases 5.10(5) times its recognition by the monoclonal antibody. We designed a ready for use reagent so no extraction of purification is needed for biological samples. Accurate calibration of monoclonal antibodies fixed on solid phase define the sensitivity of the test. This sensitivity allows histamine determination in plasma samples. The same rationale is applicable whatever tracer is used: either radiolabelled with iodine or coupled to an enzyme.

Antibodies, Monoclonal↗