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Biomedical subjects

J Martinez

Publications and source records attributed to J Martinez.

At least 325 records · Page 18Linked to original sources
PubMed1992

Gastrointestinal motor alterations induced by precipitated benzodiazepine withdrawal in rats.

The effects of benzodiazepine withdrawal on intestinal motor activity and propulsion were investigated in two groups of diazepam-dependent rats (15 mg/kg/day for 8 days). Withdrawal was precipitated by injection of two benzodiazepine antagonists (Ro 15.1788 and PK 11.95) acting on central and peripheral-type receptors, respectively. Intestinal motor activity was assessed by implanting electrodes for long-term electromyographic recordings. Gastrointestinal transit was evaluated after gavage by a marker (51CrO4Na2) and radioactivity counting. Both RO 15.1788 (15 mg/kg) and PK 11.195 (5 mg/kg) triggered an abstinence syndrome with behavioral and autonomic signs. At the intestinal level, Ro 15.1788 induced a phase of strong irregular spiking activity (173 +/- 63 min) which remained located in the duodenum. In contrast, PK 11.195 induced a period of propagated myoelectric complexes characterized by phases II and III of high amplitude. The cecal frequency was doubled during the 1st hr after withdrawal induced by the two antagonists. Both Ro 15.1788 and PK 11.195 at this dosage had no effect per se on intestinal motility in vehicle-treated rats. In the second group of rats, gastric emptying was enhanced by 49.4 and 45.6% by Ro 15.1788 and PK 11.195, respectively. In contrast, PK 11.195 was able to accelerate the intestinal transit more than did Ro 15.1788 (geometric center, 5.9 +/- 0.43 and 5.3 +/- 0.49, respectively, vs. 4.1 +/- 0.31 in control rats). Our study shows that precipitated benzodiazepine withdrawal in diazepam-dependent rats induces alterations of the intestinal myoelectrical activity leading to an increase of the gastrointestinal transit. Central and peripheral-type receptors are involved in these effects.

Animals↗
PubMed1992

Juxta-anastomotic sacciform dilation: an unusual complication of colonic stapled suture.

The commonest complications of stapling closure in gastrointestinal surgery are dehiscence, bleeding at the site of anastomosis and stenosis. Juxta-anastomotic sacciform dilation following end-to-side circular stapling anastomosis of the left colon is reported as an unusual complication. The case highlights the need for careful technique in order to obtain all the advantages offered by staplers.

Anastomosis, Surgical↗
PubMed1992

The dieffenbachia plant. Case history.

When ingested, the common house plant dieffenbachia can lead to significant toxicity and possibly death if timely medical attention is not forthcoming following initial exposure. The deleterious effects should not be overlooked especially when children are involved who, naturally curious, may bite into this innocuous looking plant. Although the patient in this case was a type II diabetic on insulin, neither hypo- nor hyperglycemia developed. There was no other significant electrolyte imbalance despite the acute stressor placed on him.

Adult↗
PubMed1991

Reduced peptide bond pseudopeptide analogues of neurotensin: binding and biological activities, and in vitro metabolic stability.

A series of pseudopeptide analogues of neurotensin was produced by systematically replacing the five peptide bonds in neurotensin-(8-13) with CH2NH (psi, reduced) bonds. All these analogues were synthesized with a free amino terminus (H derivatives) and with a N-terminal tert-butyloxycarbonyl group (Boc derivatives). The compounds were screened in vitro for agonist or antagonist activity and for metabolic stability by testing (1) their ability to inhibit the binding of radiolabelled neurotensin to homogenates of newborn mouse brain; (2) their ability to contract isolated guinea-pig ileum preparations; and (3) their degradation in the presence of rat brain homogenates. All the analogues bound to the mouse brain neurotensin receptor and all exhibited agonist activity in the guinea-pig ileum assay. Only the H- and Boc-[psi 8,9] derivatives were at least as potent as their parent compounds neurotensin-(8-13) and Boc-neurotensin-(8-13) in the binding and biological assays. All the other pseudopeptide analogues with reduced bonds at position 9-10, 10-11, 11-12 and 12-13 showed a marked reduction in potency ranging from 2 to 4 orders of magnitude. All the derivatives that were protected at their N terminus either by the presence of a Boc group or by the presence of a reduced bond at position 8-9 and 9-10 were slowly degraded by rat brain homogenates. The other derivatives were, in contrast, quite rapidly degraded. There was a good correlation between binding and biological potencies for those analogues that were resistant to degradation. Interestingly, the degradation-resistant H-[psi 8,9] compound exhibited higher binding and biological potency then neurotensin. It is therefore expected that this analogue will produce highly potent and long-lasting neurotensin-like effects in vivo, and preliminary experiments indicate that this is indeed the case.

Amino Acid Sequence↗
PubMed1991

Tissue (type II) transglutaminase covalently incorporates itself, fibrinogen, or fibronectin into high molecular weight complexes on the extracellular surface of isolated hepatocytes. Use of 2-[(2-oxopropyl)thio] imidazolium derivatives as cellular transglutaminase inactivators.

Rabbit hepatocyte surface-expressed tissue (type II) transglutaminase is shown to act as a binding site for fibrinogen or fibronectin and to covalently incorporate these glycoproteins, in addition to itself, into extracellular high molecular weight complexes. This concept is supported by the observation that a nonpeptidyl, active site-directed transglutaminase inactivator (L683685) elicited concentration-dependent (0.1-10 microM) decreases in the calcium-dependent binding and covalent cross-linking of 125I-fibrinogen, 125I-fibronectin, or [14C]putrescine by hepatocyte suspensions. In corroboration with these findings, an antiserum against rabbit liver transglutaminase, which did not cross-react with rabbit factor XIII, elicited concentration-dependent decreases in the calcium-dependent binding and covalent cross-linking of 125I-fibrinogen or [14C]putrescine by hepatocyte suspensions. Western blots of sodium dodecyl sulfate/Triton-insoluble hepatocyte fractions conducted with this antiserum, with a polyclonal antiserum against human erythrocyte transglutaminase, or with a monoclonal antibody (CUB-7401) against guinea pig liver transglutaminase detected the 80-kDa tissue transglutaminase, as well as tissue transglutaminase-immunoreactive bands of higher molecular mass (range of 90 to greater than 200 kDa). The higher molecular weight species were preferentially incorporated, in a time- and calcium-dependent manner, into very high molecular weight complexes which did not enter the stacking gel. Incorporation of these tissue transglutaminase-containing bands into the high molecular weight complexes was inhibited by L683685, indicating that cross-linking by the enzyme was responsible for the assembly of the complexes of which tissue transglutaminase was itself a component. Cellular integrins did not mediate ligand binding under the experimental conditions, as evidenced by the failure of the Arg-Gly-Asp-Ser tetrapeptide or anti-integrin antibodies to inhibit binding or cross-linking of 125I-fibrinogen or 125I-fibronectin, in the presence or absence of transglutaminase inactivators.

Animals↗
PubMed1991

Oxyntomodulin and related peptides control somatostatin secretion in RIN T3 cells.

We studied the effects of oxyntomodulin (OXM), of its C-terminal (19-37) fragment (OXM (19-37)) and of glucagon (GLU) on somatostatin release, cyclic AMP accumulation and inositol phosphate turnover in somatostatin-secreting RIN T3 cells in culture. Rapid changes in cellular free Ca2+ were also measured using fura-2. Carbachol was used as a control test agent for the parameters involving the inositol phosphate/Ca2+ cascade. OXM, GLU and OXM (19-37) were all able to stimulate somatostatin release with relative ED50 of approx. 1, 22 and 45, respectively. OXM and GLU stimulated cyclic AMP levels with relative ED50 of approx. 1 and 30, respectively, whereas OXM (19-37) was totally ineffective on this parameter. In contrast to carbachol, none of the peptides significantly modified the inositol phosphate turnover or induced rapid changes in cellular free Ca2+. We conclude that the RIN T3 cells contain a receptor-cyclic AMP system similar to that found in gastric mucosa and that this system is linked to somatostatin release. Another receptor-second messenger mechanism linked to somatostatin release is triggered by the (19-37) fragment. This mechanism is not the inositol phosphate/Ca2+ cascade triggered in the same cells by cholinergic agents.

Animals↗
PubMed1991

Oxyntomodulin and its (19-37) and (30-37) fragments inhibit histamine-stimulated gastric acid secretion in the conscious rat.

Oxyntomodulin, a hormone released from jejuno-ileum and composed of the glucagon sequence extended by a C-terminal octapeptide displays original tissue specificity for the gastric mucosa. The aim of this study was to compare the effect of oxyntomodulin on histamine (0.4 mg/kg per h)-stimulated gastric acid secretion in the conscious rat to that of three of its fragments: oxyntomodulin-(19-37) produced from oxyntomodulin by enzymatic cleavage, oxyntomodulin-(30-37) corresponding to the molecular difference between oxyntomodulin and glucagon and oxyntomodulin-(32-37) produced during proglucagon processing to glucagon. The metabolic clearance rate (MCR) in the anesthetized rat was evaluated for each peptide. Oxyntomodulin, oxyntomodulin-(19-37) and oxyntomodulin-(30-37) inhibited the histamine-stimulated gastric acid secretion dose dependently. The dose-response curves for oxyntomodulin and oxyntomodulin-(19-37) were parallel. The potency of oxyntomodulin (19-37) (ED50 approximately 70 pmol/kg) was the same as that of oxyntomodulin (ED50 approximately 35 nmol/kg) after correction of the curve for the MCR (two-fold higher for the fragment). Although the dose-response curve for oxyntomodulin-(30-37) was not entirely parallel to that of the two other peptides, its maximal inhibition (at 15 nmol/kg) was the same as that of oxyntomodulin-(19-37). Thus, oxyntomodulin-(30-37) was an efficient as the longer molecules but approximately 150-fold less potent than oxyntomodulin. The MCR for oxyntomodulin-(30-37) was approximately 250 fold higher than that of oxyntomodulin, partly explaining the difference in potency. The (32-37) fragment, which is naturally released from the endocrine pancreas, was devoid of activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Na+/Ca2+ exchange activity is increased in Alzheimer's disease brain tissues.

These studies were performed to determine the changes that occur in Na+/Ca2+ exchange activity in Alzheimer's disease (AD) brain tissues. Cerebral plasma membrane vesicles were purified by sucrose density gradient centrifugation from frozen postmortem hippocampal/temporal cortex tissue slices derived from age matched brains of normal, AD and non-Alzheimer dementia (NAD) origin (autopsy confirmed). Membrane marker assays (Na/K ATPase, muscarinic receptor, cytochrome c oxidase) revealed no change in membrane purity across different preparations. Thin-section electron microscopy revealed predominantly intact unilamellar vesicles. Vesicles were preincubated for 15 min (37 degrees C) in buffer containing 132 mM NaCl, 5 mM KCl, 1.3 mM MgCl2, 10 mM glucose and 10 mM HEPES (pH 7.4). Ca2+ uptake was initiated by diluting vesicles 20-fold with buffer containing either 132 mM NaCl or 132 mM choline chloride and 45CaCl2 then terminated by addition of 200 microM LaCl3 and rapid filtration. Ca2+ content increased rapidly at first and then maintained a steady plateau for up to 5 min. When the Ca2+ ionophore A23187 (10 microM) with 100 microM EGTA was added after 4 min, Ca2+ content was reduced to 10% of its original value. Ruthenium red (10 microM) had no effect on Ca2+ content. Na(+)-dependent Ca2+ uptake (Ca2+ content measured in choline chloride minus that measured in NaCl) was increased in AD brains as evidenced by both an increase in the initial rise in Ca2+ content and in elevated values of peak plateau Ca2+ content.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The role of capillarization in hepatic failure: studies in carbon tetrachloride-induced cirrhosis.

During the cirrhotic process, the hepatic microvascular phenotype is transformed from sinusoids (discontinuous capillaries) into continuous capillaries. This transformation has been termed capillarization. Many hepatic functions depend on the rapid, bidirectional exchange of macromolecules between plasma and hepatocytes. To determine whether capillarization contributes to hepatic failure in cirrhosis, we decided to study the plasma clearance (125I) and hepatocyte uptake (electron microscopy) of three tracers in normal and cirrhotic rats. The tracers chosen were a hemeundecapeptide with peroxidatic activity (fluid-phase pinocytosis), asialofetuin (receptor-mediated endocytosis of a medium size protein) and ferritin (receptor-mediated endocytosis of a large size protein). The results demonstrate a decreased hepatocyte uptake of hemeundecapeptide; a significant delay in plasma clearance of asialofetuin; and a minor delay in plasma clearance of ferritin, but a striking trapping of ferritin in the cirrhotic capillary basement membrane. The delayed plasma clearance in cirrhosis cannot be ascribed to a decreased number of surface receptors because, in isolated hepatocytes, the number of molecules bound per cell was equivalent in normal and cirrhotic livers. These findings support the concept of capillarization, with the formation of continuous diffusion and filtration barriers between plasma and hepatocytes, representing a significant hindrance to the bidirectional macromolecular exchange normally taking place between these two compartments. Furthermore, at least in the case of ferritin, the capillary basement membrane of cirrhotic livers seems to be the major filtration barrier. This hindrance to hepatocyte uptake, and presumably also to secretion, may be the cause (or at least a major determinant) of the hepatic failure characteristic of cirrhosis.

Animals↗
PubMed1991

Malignant papillomatosis of the common bile duct. A case diagnosed by endoscopic retrograde cholangiopancreatography.

Bile duct papillomatosis is a rare entity with a high risk of malignant change. We report the case of a 60-year-old man with malignant papillomatosis of the distal common bile duct and a separate carcinoma of ampulla of Vater. The patient had previously undergone surgery for acute cholecystitis and common bile duct calculi. Three months later the patient developed jaundice and fever. An endoscopic retrograde cholangiopancreatography demonstrated multiple filling defects adherent to the wall of the distal common bile duct. Pancreatoduodenectomy was performed with complete resection of the extrahepatic bile duct. Histologic examination showed a multicentric papillary adenocarcinoma of the common bile duct associated with an adenocarcinoma of the ampulla of Vater. The resection margins were free of tumor.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1991

In vitro influence of gastrin, oestradiol and gonadotropin-releasing hormone on HCT-15 and LoVo human colorectal neoplastic cell proliferation.

We set up in vitro several human colorectal neoplastic cell lines that we labelled "hormone-sensitive" (HS) in comparison to the original cell lines which appeared to be rather "hormone-insensitive" (HI). We used LoVo and HCT-15 human colorectal neoplastic cell lines and studied the influence of 17 beta-oestradiol (E2), gastrin and two gonadotropin-releasing hormone (GnRH) analogues, HRF and buserelin, on the proliferation of the HS and HI variants of the LoVo and HCT-15 cell lines. Cell proliferation was evaluated by a colorimetric assay, the MTT test. Our results show that E2, gastrin, HRF and buserelin did not induce a significant stimulatory influence on the HI variants of the LoVo and HCT-15 cells, i.e. the cells that were cultured in a hormone-free 10% FCS-supplemented medium. In sharp contrast, the colorectal cells cultured for 30 passages in an E2 and/or gastrin + 1% FCS-supplemented medium showed a marked tropic response to E2, gastrin, HRF and buserelin. However, the HS variants of the HCT-15 cells appeared less sensitive to the two GnRH analogues than did the HS variants of the LoVo cells.

Cell Count↗
PubMed1991

Synthetic CCK8 analogs with antagonist activity on pancreatic receptors: in vivo study in the rat, compared to non-peptidic antagonists.

The cholecystokinin octapeptide (CCK8)-derived synthetic peptides Boc-Tyr(SO3H)-Nle-Gly-DTrp-Nle-Asp-O-CH2-CH2-C6H5 (JMV179) and Boc-Tyr(SO3H)-Nle-Gly-DTrp-Nle-Asp-NH-CH2-CH2-C6H5 (JMV167) are antagonists of peripheral cholecystokinin (CCK) receptors in vitro. In the present study, antagonist activity of these peptides was studied on rat pancreatic secretion in vivo, and compared to those of other peptidic molecules and to the non-peptidic antagonists L364718, D-, L-, DL-lorglumide, and proglumide. The decreasing order of antagonist potencies on amylase release in vitro was L364718 greater than JMV179 greater than lorglumide greater than JMV167 greater than proglumide; JMV179 was 25 times less potent than L364718 and 300 times more potent than JMV167. The decreasing order of antagonist potencies on protein output in pancreatic juice in vivo was L364718 greater than JMV167 greater than JMV179 greater than lorglumide greater than proglumide; JMV167 was two times more potent than JMV179 and only 8 times less potent than L364718. Increased potency of JMV167, relative to JMV179 under in vivo conditions, is probably due to the slower rate of catabolism of the phenylethylamide group, relative to the phenylethylester group, since the metabolite issued from hydrolysis of the ester bond was totally inactive. This study shows that it is possible to obtain peptidic CCK antagonists, which are active and potent in vivo, and provides a quantitative measurement of potency changes occurring in vivo for several peptidic and non-peptidic antagonists.

Amino Acid Sequence↗
PubMed1991

Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein.

Primary rat embryo fibroblasts were transformed by a p53 mutant (alanine to valine change at amino acid 135) plus ras. This p53val135 mutant is temperature sensitive for a conformational change detected by the binding of a monoclonal antibody, PAb246, which recognizes the wild-type protein or the great majority of p53val135 at 32.5 degrees C. At 37 degrees C, both mutant and wild-type p53 conformational forms co-exist in the cells, while at 39.5 degrees C, the majority of the p53val135 in the cell is in a mutant conformation not recognized by PAb246 antibody. At 39.5 degrees C, the mutant p53 is localized in the cytoplasm of the cell. At 32.5 degrees C, the p53 protein enters the nucleus and stops the growth of these cells. At 37 degrees C where there is a mixture of mutant and wild-type p53, the wild-type p53 protein is in a complex with hsc70 and mutant p53 protein in the cytoplasm of the cell during G1. This wild-type protein enters the nucleus as the cells enter the S-phase of the cell cycle. At 32.5 degrees C, the cells stop replication and arrest at the G1/S border. After 48 hr at 32.5 degrees C, 91% of the cells are in the G1 fraction of the cell cycle. The S-phase cells appear to be immune to the p53 negative regulation of growth until they enter the next G1 period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Synthesis and biological activity of 2-phenylethyl ester analogues of C-terminal heptapeptide of cholecystokinin modified in Trp 30 region.

We have tried to evaluate the significance of the tryptophan side chain residue and of the surrounding peptide bonds in the antagonist activity of cholecystokinin analogues lacking the C-terminal amide function and having a D-tryptophan. In order to perform this study, analogues of the C-terminal heptapeptide of cholecystokinin were synthesized by replacing the C-terminal phenylalanine residue with 2-phenylethyl alcohol and by either replacing the tryptophan residue with an alanine, a norleucine and a phenylalanine residue, or introducing a "reduced peptide bond" in the tryptophan 30 region. Most of these compounds were able to reproduce only part of the response of cholecystokinin in stimulating amylase release from rat pancreatic acini, as was already observed for 2-phenylethyl ester analogues of CCK. These results point out the key role of tryptophan 30 in the biological response of cholecystokinin.

Amino Acid Sequence↗
PubMed1991

The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is antigenic in human infections.

Antibodies against the major cysteine proteinase (cruzipain) from Trypanosoma cruzi were detected in human sera obtained from patients with chronic Chagas' disease. Not only the intact 60-kDa enzyme but also its 25-kDa self-proteolysis fragment are antigenic in vivo. Although T. cruzi antigens 13 and 36 also reacted with the apparently monospecific antiproteinase serum, the antigenicity of cruzipain to human patients is genuine, since its reactivity was not modified by the adsorption of human sera with the recombinant proteins 13 and 36.

Animals↗
PubMed1991

Influence of mode of storage and drying of fodder on thermophilic actinomycete aerocontamination in dairy farms of the Doubs region of France.

Airborne contamination by thermophilic actinomycetes, micromycetes and Gram negative bacteria was determined on 34 dairy farms and related to fodder drying and storage methods. Eighteen farms had a barn drying system, eight with additional heating; the remaining 16 had traditional fodder storage methods. Three air samples were obtained for each farm with a six stage Andersen sampler. The thermophilic actinomycetes were identified as Streptomyces and the dominant micromycetes as Aspergillus spp; there was no relation between the levels of these organisms. There were fewer thermophilic actinomycete colonies per Petri dish (stage 5 on the Anderson sampler) on farms with barn drying than on those with traditional storage (median (range) 7 (0-2628) and 56 (4-2628) respectively). The three farms where no thermophilic actinomycetes were found had barn drying with heating and the four most modern farms had lower thermophilic actinomycete colony counts than the others (median (range) 3 (0-10) and 48 (0-2628)). The level of thermophilic actinomycetes and, to a lesser degree, of micromycetes was higher where the farmer had farmer's lung. Thermophilic actinomycetes of the genus Streptomyces are probably the antigens associated with farmer's lung in the Doubs, and modern farms with barn drying and heating furnish some protection against this disease.

Actinomycetales Infections↗
PubMed1991

Valve and great vessel stenosis: assessment with MR jet velocity mapping.

For measurement of poststenotic jet velocities with magnetic resonance (MR) imaging, the authors reduced the echo time (TE) of the field even-echo rephasing (FEER) velocity mapping sequence from 14.0 to 3.6 msec, so minimizing the problem of MR signal loss from turbulent fluid. In vitro use of rotating disk and stenotic flow phantoms confirmed that the 3.6-msec TE sequence enables accurate measurement of jet velocities of up to 6.0 m/sec (r = .996). Peak jet velocity measurements were made with MR imaging in 36 patients with stenosis of native heart valves (n = 9), conduits (n = 19), or Fontan connections (n = 2) or with aortic coarctation (n = 6). Peak velocity measurements made with MR imaging agreed well with measurements made with Doppler ultrasound (US), which were available in 18 cases (standard deviation = 0.2 m/sec). Velocity mapping with fast-echo MR imaging is likely to have considerable importance as a noninvasive means of locating and evaluating stenoses, particularly at sites inaccessible to US, but care must be taken to prevent errors caused by malalignment, signal loss, phase wrap, or partial-volume effects.

Adult↗