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J Martinez

Publications and source records attributed to J Martinez.

At least 379 records · Page 21Linked to original sources
PubMed1989

Synthesis of gastrin antagonists, analogues of the C-terminal tetrapeptide of gastrin, by introduction of a beta-homo residue.

A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.

Animals↗
PubMed1989

Synthesis and biological activity of some partially modified retro-inverso analogues of cholecystokinin.

Syntheses of some partially modified retro-inverso analogues of the C-terminal octa- or heptapeptide of cholecystokinin are described. These analogues (in which the C-terminal carboxamide was deleted or not) were obtained by reverting one or several peptide bonds in the parent molecule. All these compounds were able to inhibit binding of labeled CCK-8 to rat pancreatic acini and guinea pig brain membranes and to stimulate amylase release from rat pancreatic acini with various potencies. Some of these derivatives reproduce only part of the biological response of CCK on amylase release.

Amino Acid Sequence↗
PubMed1989

Synthesis and biological activities of some cholecystokinin analogues substituted in position 29 by a beta-alanine.

Syntheses of analogues of the C-terminal heptapeptide of cholecystokinin are described. These analogues were obtained by replacing glycine 29 by a beta-alanine. The C-terminal phenylalanine amide was in some cases substituted by 2-phenylethyl alcohol and/or residues of the C-terminal tetrapeptide by their D-enantiomers. These compounds were tested for their action on stimulation of amylase release from rat pancreatic acini and for their ability to inhibit binding of labeled CCK to rat pancreatic acini and guinea pig brain membranes. Some of these derivatives behaved as CCK receptor antagonists.

Alanine↗
PubMed1989

1H n.m.r. conformational studies on the C-terminal octapeptide of oxyntomodulin, a beta-turn locked by a salt bridge.

The octapeptide Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala (Arg4 in the human sequence) is the C-terminal part of porcine oxyntomodulin, an endogeneous peptide which is a potent inhibitor of stimulated acid secretion. This octapeptide exhibits the whole range of biological activities of the parent hormone. In the present work we report an 1H n.m.r. investigation of the conformational properties of the octapeptides of pig and human sequences in dimethylsulfoxide-d6 (DMSO) solution. The various resonances were assigned on the basis of two-dimensional COSY and NOESY experiments. Other experiments such as (i) temperature and concentration dependence of the amide proton chemical shifts, (ii) effects of ionic strength, (iii) comparison of the spectra with different analogues, were performed. We showed that in DMSO, the conformation of the octapeptide is directly related to the ionisation state of the C-terminus carboxyl group of alanine. In carboxylic state, the peptide adopts an extended conformation, while in the carboxylate state the four last residues (Asn-Asn-Ile-Ala) are involved in a type II beta-turn structure probably locked by a salt bridge between the carboxyl group of Ala8 and the epsilon ammonium group of Lys4 (or the guanidinium group of Arg4). These observations provide an insight into the possible conformational tendencies of this peptide in biological media.

Amino Acid Sequence↗
PubMed1989

Passive transfer of contact sensitivity to colophony as a complication of an allogenic bone-marrow transplant.

A 29-year-old woman developed allergic contact dermatitis from colophony 1 year after an allogenic bone-marrow transplant for refractory anaemia. The donor had a previous history of contact dermatitis from colophony, with a positive patch test. Although we cannot absolutely exclude active sensitization, it seems highly improbable because host immunity is severely restricted by the chemoradiotherapy used to prepare marrow graft recipients. The clinical data therefore suggest that sensitivity to colophony was passively acquired through marrow transplantation.

Adult↗
PubMed1989

Analysis of a region of the human cytomegalovirus (AD169) genome coding for a 25-kilodalton virion protein.

In a previous study, we reported the isolation of a lambda gt11 cDNA clone (C3) for a virus message that mapped to the HindIII R fragment (human cytomegalovirus [AD169]). In this report, we further analyze transcription from this region of the genome. C3 was used to probe Northern (RNA) blots of RNA isolated from infected cells. Two abundant messages, 1.3 and 1.6 kilobases (kb) in size, were detected at 62 h postinfection (p.i.). Examination of different time points determined that the 1.6-kb mRNA accumulated in infected cells between 24 and 48 h p.i. and was classified as a late message. The 1.3-kb message was transcribed early in infection and was initially detected around 12 h p.i. Both transcripts were suppressed when infected cells were treated with inhibitors of DNA synthesis. Sequencing and S1 analysis identified the 5' ends of these two messages within 240 nucleotides of each other. Two CAAT-TATA motifs were found upstream of the 1.3- and 1.6-kb mRNA initiation sites, which suggested that the promoters were also closely associated. Antisera made to the fusion protein, synthesized from the C3 clone, detected a 25-kilodalton (kDa) virus protein found in infected cells and purified virions. Western blot (immunoblot) analysis of infected-cell proteins at various times after infection demonstrated that the accumulation of the 25-kDa protein coincided with the appearance of the 1.6-kb message. Therefore, we conclude that the 25-kDa virion protein is translated from the 1.6-kb message.

Animals↗
PubMed1989

Coarctation of the aorta: MR imaging in late postoperative assessment.

Thirty-six patients were studied with magnetic resonance (MR) imaging 2-29 years after repair of coarctation of the aorta, and the findings were compared with clinical data and results of echocardiography, catheterization, angiography, and surgery. A satisfactory echocardiographic examination of the isthmus was achieved in 28 patients. Comparison with data from gradient measurements at catheterization and Doppler ultrasound shows that the reduction of lumen diameter correlates well with the gradient and that restenosis at the site of the repair can be suspected when the percentage of stenosis at the isthmus is greater than 50%. MR imaging showed a Dacron patch aneurysm in three patients. Cine MR imaging showed systolic signal loss in the ascending aorta that was presumed to be due, among other factors, to turbulent flow generated from a bicuspid valve. Similar signal loss was seen in the descending aorta distal to the site of the coarctation repair, but this was not related to the presence or absence of a gradient. Aortic compliance measured from transverse MR systolic and diastolic images was abnormally low, suggesting it may be a factor causing systolic hypertension after coarctation repair. MR imaging is a reliable and accurate noninvasive method likely to supersede other methods of assessing the aorta and isthmus following coarctation repair.

Adolescent↗
PubMed1989

Receptor occupation, calcium mobilization, and amylase release in pancreatic acini: effect of CCK-JMV-180.

We examined the relationships between receptor occupation, calcium mobilization, and stimulated amylase release for cholecystokinin octapeptide (CCK-8) and for CCK-JMV-180, an analogue of the COOH-terminal heptapeptide of CCK having the structure Boc-Tyr(SO3)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester using dispersed acini from rat pancreas. CCK-8 and CCK-JMV-180 each bind to two classes of CCK receptors: one class has a high affinity for CCK-8 and CCK-JMV-180 and the other class has a low affinity for CCK-8 and CCK-JMV-180. Mobilization of cellular calcium was assessed by measuring cytosolic calcium with a fluorescent indicator and by measuring outflux of radioactive calcium from preloaded cells. In terms of causing an increase in cytosolic calcium or an increase in calcium outflux, CCK-JMV-180 was 50-60% as efficacious as CCK-8. Analysis of the relationship between receptor occupation and calcium mobilization caused by CCK-8 and CCK-JMV-180 in combination indicates that calcium mobilization is caused by occupation of low-affinity CCK receptors. Comparison of the dose-response curve for calcium mobilization and amylase release stimulated by CCK-8 or CCK-JMV-180 indicates that very low concentrations of each peptide stimulate amylase release without causing detectable calcium mobilization. At these very low concentrations, CCK-8 or CCK-JMV-180 do not cause potentiation of amylase release when combined with vasoactive intestinal peptide.

Amylases↗
PubMed1989

A new CCK analogue differentiates two functionally distinct CCK receptors in rat and mouse pancreatic acini.

Analysis of the competitive inhibition of 125I-labeled cholecystokinin octapeptide (CCK-8) binding to isolated rat or mouse pancreatic acini showed that in both species CCK-8 interacts with two different affinity sites. A newly synthesized CCK analogue modified at the COOH-terminal phenylalanine residue totally inhibited 125I-CCK binding. This interaction occurred with sites of a single affinity in rat acini but with two different affinity sites in mouse acini. When acini were incubated with increasing concentrations of CCK-8, a biphasic stimulation of amylase release was observed. By use of rat acini, the analogs stimulated amylase release but caused no inhibition at supramaximal concentrations. By contrast, in mouse pancreatic acini, analogues showed a biphasic stimulation of amylase release similar to CCK-8. Both CCK-8 and the analogue stimulated [3H]leucine incorporation into protein at low concentrations in rat pancreatic acini. Higher concentrations of CCK-8 profoundly inhibited [3H]leucine incorporation, whereas the analogue had no inhibitory effect. Moreover, the analogue at higher concentrations blocked the inhibition of [3H]leucine incorporation caused by CCK-8 but did not affect carbamylcholine-induced inhibition. In mouse acini, however, the CCK analogue inhibited [3H]leucine incorporation similar to the effect of CCK-8. The results support the concept that occupancy of distinct affinity sites or states of the CCK receptor is associated with specific biological actions. A model of the CCK receptor is proposed in which two interchangeable affinity states exist. By occupying all the receptors in only one state, the new CCK analogues serve as partial agonists of some and antagonists of other actions of CCK.

Amylases↗
PubMed1989

Changes in collagen synthesis by human bone marrow fibroblasts with progressive subcultivation.

Bone marrow fibroblasts from normal and leukemic patients were used to investigate the relationship between serial subcultivation and changes in collagen synthesis. A regime was established to generate subcultures up to 35 cumulative population doublings (CPDs) in normal cells and to 9 CPDs in leukemic cells. In both types of cells, collagen synthesis decreased as subcultivation progressed. In normal cells, collagen synthesis was reduced to 10% of the original levels at 18 CPDs and in leukemic cells at 8 CPDs. In normal fibroblasts, collagen synthesis was more profoundly affected than overall protein synthesis by subcultivation. In acute lymphoblastic leukemia-derived fibroblasts, the decrease in collagen synthesis paralleled that of total protein.

Bone Marrow↗
PubMed1989

Inhibitory effect of the C-terminal octapeptide of oxyntomodulin on pentagastrin-stimulated gastric acid secretion in man.

The effect of the C-terminal octapeptide of human oxyntomodulin (KA-8) on pentagastrin-stimulated gastric acid secretion was studied versus placebo in eight human volunteers after an overnight fast, using a double-blind randomized protocol. KA-8 (7.5 nmol/kg body weight) was bolus-injected at a plateau stimulation obtained with pentagastrin (3 micrograms/kg/h). KA-8 significantly decreased the volume secreted by 36% (p less than 0.025) and the acid output by 32% (p less than 0.025) 20 min after injection. The areas under the curve were significantly reduced for volume and acid output during the 1st h after peptide injection.

Adult↗
PubMed1989

[Glucagon is processed to the (19-29) fragment at the level of the hepatocyte membrane].

Upon incubation with hepatic plasma membranes, glucagon is processed into its (19-29) C-terminal fragment. This suggests that, in physiological conditions, glucagon is processed in a target tissue at the level of its Arg17-Arg18 basic doublet, leading to the production of a fragment which is known to display an original biological specificity, namely the modulation of the calcium pump present in hepatocyte plasma membrane.

Animals↗
PubMed1989

[Campylobacter pylori in children and adults subjected to endoscopy, correlation of endoscopic, bacteriologic and histopathologic findings].

Campylobacter pylori has been associated to peptic ulcer and gastritis. We investigated the presence of C pylori in 17 children and 50 adults who needed endoscopy to investigate upper gastrointestinal symptoms. Gram stain, Whartin-Starry stain and the urease test were used to identify the germ; best results were obtained with the Gram stain. C pylori was present in 5.8% of children and 88% of adults, including all patients with peptic ulcer and 36 out of 39 with histologic evidence of gastritis. However, the germ was also found in 79% of patients with a normal mucosa. Our results suggest that C pylori is frequently present in gastric mucosa of children and adults with upper gastrointestinal problems. Further studies are needed to elucidate its possible pathogenic role in gastritis or peptic ulcer.

Adolescent↗
PubMed1988

Dissociation of fibrinogen and fibronectin binding from transglutaminase-mediated cross-linking at the hepatocyte surface.

The interaction of fibrinogen and fibronectin with hepatocytes has been dissociated into distinct binding and cross-linking steps. Binding and cross-linking of 125I-labeled ligands were both decreased by transglutaminase inhibitors, but not by heparin or hirudin. Transglutaminase activity was manifest by Ca2+-dependent incorporation of [14C]putrescine into cells. Preferential cross-linking of fibrinogen A alpha over gamma chains, and lack of inhibition by heparin or hirudin indicates the involvement of tissue transglutaminase, and not Factor XIIIa. Hepatic transglutaminase activity, as well as binding and cross-linking of fibrinogen and fibronectin, were maximally supported by Ca2+, partially supported by Mn2+ and Sr2+, and markedly decreased by Mg2+ and Ba2+. In contrast, Co2+ supported binding but not cross-linking or transglutaminase activity, indicating that binding and cross-linking are dissociable events. This conclusion was corroborated by the finding that fibrinogen fragments D95 and D78 both inhibited Ca2+-dependent fibrinogen binding without being cross-linked themselves. Ligand binding in the presence of either cation was localized to the cell surface as evidenced by its trypsin sensitivity. Thus, fibrinogen and fibronectin binding to hepatocytes is independent of transglutaminase activity, whereas cross-linking of these adhesive macromolecules requires an enzymatically active cellular transglutaminase. In addition, fibrinogen binding appears to be mediated by molecular determinants present in fragment D78.

Animals↗
PubMed1988

Development of an oxyntomodulin/glicentin C-terminal radioimmunoassay using a "thiol-maleoyl" coupling method for preparing the immunogen.

Oxyntomodulin (OXM) and glicentin, two peptides processed from proglucagon, both contain the glucagon sequence and a C-terminal basic octapeptide, KRNRNNIA extension. A method to produce antibodies, directed specifically toward the C-terminal extension of these two peptides, was developed; it consisted of the use of thioled bovine serum albumin conjugated with the synthetic N-maleoyl C-terminal octapeptide as the immunogen. Three rabbits (FAN, LEG, and PIP) generated antisera with affinity constants close to 5 X 10(10) M-1. In the radioimmunoassay system, these antisera showed a 100% cross-reactivity with OXM, partially purified rat and human glicentin, and the C-terminal 19-37 OXM fragment. They displayed no cross-reactivity toward the glucagon molecule. The cross-reactivity of C-terminal fragments of OXM demonstrated that the epitope involves the C-terminal hexapeptide and that the two last amino acid residues are essential for the binding. The high-performance liquid chromatography elution profiles of human jejunum or rat intestinal extracts obtained by radioimmunoassay with LEG antiserum showed two major peaks which had the same retention times as OXM and glicentin markers. Thus, the major end products in the human and rat small intestine are OXM and glicentin. In human or rat pancreas, the two main peaks detected were glucagon and the C-terminal hexapeptide of OXM/glicentin. Small amounts of OXM were also found in pancreas, whereas no significant quantities of glicentin could be detected. The "thiol-maleoyl" coupling method described here, and applied to produce C-terminal OXM/glicentin specific antisera, might be of general use to obtain antibodies against a well-defined epitope.

Animals↗