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Biomedical subjects

J Martinez

Publications and source records attributed to J Martinez.

At least 307 records · Page 17Linked to original sources

Spontaneous evolution of cytoplasmic lectin binding and nuclear size and deoxyribonucleic acid content in human colorectal cancers grafted onto nude mice.

BACKGROUND: The development of certain biologic characteristics in human colorectal tumor xenografted onto nude mice are described with respect to their precocious passages, i.e., passaging below 10 onto athymic mice. EXPERIMENTAL DESIGN: The biologic characteristic monitoring involved the determination of modifications occurring in cytoplasmic lectin binding and spontaneous development in nuclear size and DNA content. The lectin immunohistochemistry included the characterization of staining modifications in the glandular parts of the colorectal xenografts of wheat germ, Dolichos biflorus, peanut, Solanum tuberosum and Ulex europaeus I agglutinins. The nuclear modifications were monitored by means of the digital cell image analyses of Feulge-stained nuclei. RESULTS: The results show that although the xenografted human colorectal lines may be relatively stable according to their macroscopic growth over serial passaging, certain of their microscopic characteristics develop markedly. Three lectins, i.e., wheat germ agglutinin, Solanum tuberosum, and Ulex europaeus I, showed a glandular binding which remained relatively stable over serial passaging, whereas the peanut binding exhibited some variations and the DBA binding progressively disappeared. These cytoplasmic modifications occurring over time were less pronounced than those that occurred with respect to nuclear measurements, i.e., size and DNA content. CONCLUSIONS: Nuclear DNA content heterogeneity as revealed by DNA histogram typing rather than by DNA index assessments increased markedly in the colorectal xenografts over their serial passaging on nude mice.

Animals↗

Pharmacological characterization of new cholecystokinin analogues.

New analogues of cholecystokinin-7 (CCK-7) modified at amino acid residues 5 and 7 were assayed for their effect on gall bladder, pancreatic secretion, food intake (anorectic activity), amount of rearing (sedative activity) and analgesia, as well as their ability to inhibit 125I-CCK-8 binding to pancreatic cell membrane receptors and brain membrane receptors. The results were compared to the activities of standard compounds, CCK-8, cerulein, BOC-CCK-7 (BOC = tertbutyloxycarbonyl) and BOC-[Nle2,Nle5]CCK-7. All analogues exhibited agonistic effects. Their anorectic activity was significantly prolonged.

Amylases↗

JMV 449: a pseudopeptide analogue of neurotensin-(8-13) with highly potent and long-lasting hypothermic and analgesic effects in the mouse.

We recently reported that H-Lys psi (CH2NH)Lys-Pro-Tyr-Ile-Leu-OH (JMV 449), a pseudopeptide analogue of neurotensin-(8-13) with a reduced CH2NH bond in position 8-9, was about 3 times more potent than neurotensin in binding to mouse brain membranes and in contracting the guinea-pig ileum, and was markedly more resistant to degradation than neurotensin when exposed to rat brain membranes. In the present study, we compared the time courses and dose-response relationships for the ability of i.c.v. injected neurotensin and JMV 449 to elicit hypothermia and analgesia (tail-flick test) in the mouse. The results show that the pseudopeptide analogue behaved as a highly potent and long-lasting neurotensin agonist in these two in vivo bioassays. The analogue should prove very useful for studying the effects of chronic neurotensin receptor stimulation in vitro and in vivo.

Amino Acid Sequence↗

Effects of thiorphan, bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the recovery of neurotensin and neuromedin N released from mouse hypothalamus.

The effects of the endopeptidase 24.11 ('enkephalinase') inhibitor thiorphan, the aminopeptidase inhibitor bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the K(+)-evoked release of immunoreactive neurotensin and neuromedin N (iNT and iNN) from mouse hypothalamic slices were examined. (JMV 390-1 inhibits several metallopeptidases including endopeptidases 24.11, 24.15 and 24.16, and aminopeptidase N equipotently with Ki values around 50 nM.) Thiorphan increased the recovery of released iNT nearly 2-fold and had no effect on iNN. Bestatin produced a 4-fold increase in iNN recovery and was inactive on iNT. Finally, iNT and iNN recoveries were increased up to 4- and 5-fold, respectively, by JMV 390-1. These results show that in the mouse hypothalamus endopeptidase 24.11 participates with other metalloendopeptidases to the degradation of endogenously released NT while endogenously released NN is principally degraded by aminopeptidase(s).

Amino Acid Sequence↗

Exercise tolerance in panic disorder patients.

Sixteen panic patients and fifteen normal controls performed submaximal exercise testing on a bicycle ergometer. Only one patient subject panicked. Biochemical, physiological, and psychological data showed similar exercise tolerance in both patients and controls. Exercise-induced distress and lactate increment do not appear to cause panic attacks.

Adult↗

Pharmacological studies on CCKB receptors in guinea pig synaptoneurosomes.

Preliminary studies on CCK receptors in the central nervous system were carried out on guinea pig cerebral cortical synaptoneurosome preparations. In binding assays, the range of affinity of CCK-8, Boc-[Nle28,Nle31]CCK-7, a potent CCK analog, Boc-[Leu31]CCK-4 and of the two benzodiazepine CCK receptor antagonists L-365,260 and MK-329, is in agreement with the presence of CCKB receptors on this model. The effects of Boc-[Nle28,Nle31]CCK-7 on inositol phosphates, cAMP accumulation and 45Ca2+ efflux were investigated. Neither inositol phosphate nor cAMP accumulations could be observed. On the other hand, evidence of Boc-[Nle28,Nle31]CCK-7-, CCK-8- and Boc-[Leu31]CCK-4-induced 45Ca2+ efflux was found in a dose-dependent manner. The CCKB-selective receptor antagonist L-365,260 and, with a weaker efficiency, the CCKA-selective receptor antagonist MK-329, are able to block a maximal effect of Boc-[Nle28,Nle31]CCK-7-induced 45Ca2+ efflux, suggesting that CCKB receptors may regulate calcium ion mobilization.

Animals↗

Cystatin C secretion by rat glomerular mesangial cells: autocrine loop for in vitro growth-promoting activity.

Cystatin C, the major inhibitor of the cysteine proteinases found in human and rat body fluids, is particularly abundant in seminal plasma and cerebrospinal fluid. In a precedent report, we have evidenced noteworthy levels of cystatin C in rat kidney cortex. In the present study, we show that rat mesangial glomerular cells produce cystatin C. Immunoprecipitation of extracts of metabolically labeled cells and culture media showed that the synthesized cystatin C is a 15.5 +/- 0.5 kDa protein. The protein was released into the culture supernatant (1.6 +/- 0.26 micrograms/10(6) cells/24 h). Urinary rat cystatin C and PPPR synthetic peptide (5-8 N-terminal sequence of rat cystatin C) increased mesangial cell proliferation. Affinity chromatography on Ultrogel-avidin-biotin-PPPR of extracts of metabolically labeled cells indicate the existence of a PPPR binding protein of 46 kDa. The results described in this work suggest, for glomerular rat mesangial cells in vitro, an autocrine regulation of proliferation by cystatin C.

Amino Acid Sequence↗

Noradrenergic function in panic disorder. Effects of intravenous clonidine pretreatment on lactate induced panic.

To assess the role of noradrenergic stimulation during lactate-induced panic, ten patients with panic disorder who panicked during a standard sodium-lactate infusion underwent a repeat infusion following intravenous clonidine pretreatment. Although clonidine significantly lowered prelactate systolic blood pressure, the drug did not significantly lower prelactate anxiety levels, as reflected by the Acute Panic Inventory (API). Clonidine blocked lactate-induced panic in four of ten subjects, a significant effect. Clonidine treatment also significantly attenuated lactate-panic symptoms, as reflected by time to panic and API comparison between trials. Nevertheless, over half the subjects still panicked in response to lactate despite clonidine. This preliminary study suggests that reduction of central noradrenergic activity by clonidine, at least at the dosage levels employed in the current study, only partially attenuates panic response to lactate. Noradrenergic theories of panic may not therefore fully account for lactate panicogenesis.

Adult↗

N-acetyl oxyntomodulin30-37: pharmacokinetics and activity on gastric acid secretion.

Oxyntomodulin, an intestinal hormone which inhibits gastric acid secretion, is composed of glucagon and a C-terminal octapeptide. This octapeptide mimics the biological activity of the hormone. We have studied the activity of the N-acetyl octapeptide, partially protected against enzymatic degradation, on pentagastrin-, histamine- and milk meal-stimulated secretion in conscious rats and compared it to that of oxyntomodulin and its derivatives. The N-acetylated octapeptide had a 3-fold higher potency than the octapeptide on pentagastrin-stimulated secretion. On histamine-stimulated secretion, the differences between the acetylated and the free octapeptides were that the former displayed a dose-response curve parallel to that of oxyntomodulin and a 4-fold higher potency. The increase in potency appears to be related in part to a decrease in the metabolic clearance rate in vivo (6-fold) and, in vitro, to an increase in half-life (3-fold) when incubated with rat liver plasma membranes. Similarly to the free octapeptide, the acetylated form decreased acid secretion stimulated by a milk meal, when infused before the meal. Acetylation of the Lysine side chains resulted in a totally inactive molecule. The results indicate that acetylating the N-terminus of the octapeptide of oxyntomodulin increases the similarities with the natural hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

Reduction of cardiovascular side effects associated with ocular administration of metipranolol by inclusion in polymeric nanocapsules.

A new formulation of metipranolol base for ophthalmic administration was developed consisting of a colloidal suspension of polyepsiloncaprolactone nanocapsules with an oily core (Migliol 840) in which the drug is dissolved. Physicochemical properties of the nanocapsules show that the polymer coating around the oily droplets causes an important reduction of the droplet size, with no significant modification of the surface charge noted. When this formulation was administered to rabbits, a reduction of intraocular pressure similar to that seen with commercial eye drops was observed. Nevertheless, the evaluation of the cardiovascular side effects clearly showed lower conjunctival absorption of the encapsulated drug compared with the commercial drops. The direct (bradycardia) and the indirect evaluation (based on the study of the influence on the hypotensive and positive chronotropic effects of isoprenaline) showed that blockage of beta-adrenoreceptors was reduced greatly by the topical administration of the new formulation.

Animals↗

The effect of gastrin on growth of human stomach cancer cells.

Gastrin is known as a trophic factor for some stomach and colorectal cancer cells; however, the roles of gastrin receptors and the intracellular signal transduction pathways by which gastrin regulates cell growth are still unknown. The authors examined the effect of synthetic human gastrin-17 on growth of human stomach cancer cells (the parent line, AGS-P, and two different clones, AGS-10 and AGS-12), which were established (and have been maintained) in our laboratory. Gastrin stimulated growth of AGS-P and AGS-10 cells, which have gastrin receptors, in a dose-dependent fashion. A highly selective gastrin receptor antagonist, JMV 320, inhibited the growth-stimulatory effect of gastrin on AGS-P cells in a dose-dependent fashion. Concentrations of gastrin (10(-8) to 10(-6) M), which stimulated growth of AGS-P cells, did not affect either cyclic adenosine monophosphate production or phosphatidylinositol hydrolysis. Gastrin (10(-11) to 10(-5) M) mobilized calcium from the intracellular organelles to increases intracellular calcium level in AGS-P cells. The AGS-12 clone has no gastrin receptors, and gastrin did not affect growth or mobilization of intracellular calcium in these cells. Our findings indicate that gastrin stimulates growth of AGS cells through a mechanism that involves binding to specific gastrin receptors that are linked to the system for mobilization of intracellular calcium.

Amino Acid Sequence↗

Enterohemorrhagic Escherichia coli associated with hemolytic-uremic syndrome in Chilean children.

A clinicoepidemiological study was undertaken to determine if enterohemorrhagic Escherichia coli (EHEC) was associated with hemolytic-uremic syndrome (HUS) in children in Santiago, Valdivia, and Temuco, Chile. Prospective surveillance detected 20 hospitalized cases of HUS in children less than 4 years of age in these cities from March 1988 to March 1989. Each HUS patient was matched (by sex and age) with two control children (hospitalized elective-surgery patients). To detect EHEC, DNA from stool culture isolates of E. coli was detected by hybridization with biotin-labelled DNA probes specific for the EHEC virulence plasmid, Shiga-like toxin I (SLT-I) or SLT-II. Stool cultures from 6 of 20 cases (30%) and from 2 of 38 controls (5.3%) yielded EHEC (P = 0.0158). EHEC isolates from all HUS cases hybridized with the EHEC plasmid probe and with probes for SLT-I or -II (or both). The serogroups of the isolates included O157, O26, and O111. EHEC causes HUS in Chile, and the biotinylated gene probes are practical diagnostic tools for epidemiologic studies.

Bacterial Toxins↗

[Post-varicella disciform keratitis].

Varicella disciform stromal keratitis is rare. It occurs several weeks or months after the skin rash. We report 4 cases in children, two of whom developed one or more recurrent episodes. Treatment based on local steroids was long and difficult to dose. One case treated with oral aciclovir did not show a better clinical course than the other patients.

Chickenpox↗