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Biomedical subjects

A Sala

Publications and source records attributed to A Sala.

At least 181 records · Page 10Linked to original sources
PubMed1991

Growth properties, differentiation capacity and oncogene expression in metastatic and nonmetastatic Friend leukemia cell variants.

The aims of this study were: (1) to characterize the biologic properties of the WGA-resistant (WR) Friend leukemia cells (FLC) as compared to the original nonmetastatic or highly metastatic FLC; (2) to investigate the possible correlations between the expression of some oncogenes (i.e., c-myc, H-ras and K-ras) and the in vitro and in vivo behavior of FLC. The tumorigenic behavior of the different FLC types strongly depended on the site of tumor injection. Both WR FLC and in vitro passaged FLC did not grow as ascites (when injected intraperitoneally) and developed large solid tumors (when injected subcutaneously), without forming any spleen or liver metastasis. In contrast, in vivo passaged FLC rapidly formed hemorrhagic ascites when injected intraperitoneally; the subcutaneous injection of these cells resulted in the development of solid tumors, which were smaller than the other FLC tumors, but capable of metastasizing to the liver and to the spleen. No significant differences were observed in the in vitro growth characteristics and cell cycle parameters among the different FLC types under various experimental conditions (i.e., FCS concentration or cell seeding densities). Similarly to the metastatic in vivo passaged parental cells, WR FLC exhibited a much lower erythroid differentiation after in vitro addition of either dimethyl sulfoxide or hexamethylene bisacetamide than the in vitro passaged FLC. High levels of c-myc oncogene mRNA were expressed in all FLC variants; no major variations in the c-myc expression were observed in FLC cultivated in medium supplemented with different FCS concentrations and/or seeded at various cell densities. In addition, no changes in the expression of H-ras or K-ras were observed between the different FLC types.

Acetamides↗
PubMed1990

Leukotriene E4 elimination and metabolism in normal human subjects.

Radiolabeled leukotriene (LT) E4 was infused into three healthy subjects in order to assess the production and elimination of sulfidopeptide leukotriene metabolites in urine. Three different radiolabeled tracers were employed, [14,15-3H]LTE4, [35S]LTE4, and [14C] LTE4 in five separate infusion studies. There was a rapid disappearance of radioactivity from the vascular compartment in an apparent two-phase process. The first elimination phase had an apparent half-life of approximately 7 min. Radioactivity quickly appeared in the urine with 10-16% eliminated during the first 2 h following intravenous infusion; 7%, 2-5 h; 4%, 5-8 h; 4%, 8-15 h; and 1.5%, 15-24 h from the [14C] LTE4 experiments. Unmetabolized LTE4 was the major radioactive component in the first urine collection, but at later times two more polar compounds predominated. After extensive purification by normal phase-solid phase extraction and reverse-phase high performance liquid chromatography, these compounds were characterized by UV spectroscopy, co-elution with synthetic standards, negative ion electron capture gas chromatography/mass spectrometry, and tandem mass spectrometry. The two major urinary metabolites were structurally determined to be 14-carboxy-hexanor-LTE3 and the conjugated tetraene, 16-carboxy-delta 13-tetranor-LTE4. Three other minor metabolites were detectable in the first urine collection only and were characterized by co-elution with synthetic standards as 16-carboxy-tetranor-LTE3, 18-carboxy-dinor-LTE4, and 20-carboxy-LTE4. omega-Oxidation and subsequent beta-oxidation from the methyl terminus appeared to be the major metabolic fate for sulfidopeptide leukotrienes in man. The accumulation of the 14-COOH-LTE3 and 16-COOH-delta 13-LTE4 may reflect a rate-limiting step in further oxidation of these compounds which places a conjugated triene or conjugated tetraene, respectively, two carbons removed from the CoA ester moiety. Also in the first urine collection there was another minor metabolite identified as N-acetyl-LTE4, however, no subsequent beta-oxidation of this metabolite was observed. The major metabolites of LTE4 might be useful in assessing in vivo production of sulfidopeptide leukotrienes in humans.

Adult↗
PubMed1990

Prostaglandins and gastric mucosal protection by esaprazole in rats.

Esaprazole, N-cyclohexyl-1-piperazineacetamide monohydrochloride, was studied for its activity to prevent gastric mucosal damage induced by several necrotizing agents in the rat. Its effects on acid gastric secretion and the role of gastric mucosal prostaglandin generation were also investigated. Esaprazole, given orally, dose dependently prevented the formation of mucosal damage induced by absolute ethanol, 0.2 N NaOH or 0.6 N HCl. This activity occurred at doses lower than the antisecretory doses. Esaprazole was also found to increase the gastric mucosal prostaglandin content but at doses that exceeded the cytoprotective doses. The failure of indomethacin to impair the gastric mucosal protection provided by esaprazole suggests that mechanisms other than mobilization of endogenous prostaglandins may be involved.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Mediator release after endobronchial antigen challenge in patients with respiratory allergy.

The aim of the present study was to evaluate the release of some potential mediators of allergic reactions, such as histamine, peptide leukotrienes (LTs), LTB4 and prostaglandin D2 (PGD2), in bronchoalveolar lavage (BAL) fluids from 11 patients with respiratory allergy (eight with bronchial asthma and three with allergic rhinitis), who underwent specific endobronchial challenge. Histamine, peptide LT, and PGD2 levels in BAL fluids increased significantly after antigen stimulation both in patients with asthma and in patients with rhinitis. By contrast, LTB4 concentration was always below the limits of detection of the radioimmunoassay. In patients with asthma, histamine concentration increased from 5.3 +/- 0.6 ng/ml in lavages obtained before provocation to 20.2 +/- 5.8 ng/ml (mean +/- SEM; p less than 0.04) 5 minutes after bronchoprovocation. Peptide LTs increased from 0.32 +/- 0.08 to 0.82 +/- 0.21 ng/ml (p less than 0.02) and PGD2 from 0.06 +/- 0.01 ng/ml to 0.36 +/- 0.09 ng/ml (p less than 0.02). Elevated histamine, peptide LT, and PGD2 concentrations were also found in the 15-minute postchallenge BAL fluids. Similar results were obtained in patients with rhinitis. Histamine concentration was 3.4 +/- 0.6 ng/ml in prechallenge bronchial lavages and 11.3 +/- 1.7 ng/ml in postchallenge lavages; peptide LTs increased from 0.13 +/- 0.008 ng/ml to 0.73 +/- 0.21 ng/ml, and PGD2 from 0.05 +/- 0.01 ng/ml to 0.26 +/- 0.06 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Contractile and binding activities of structural analogues of LTC4 in the longitudinal muscle of guinea-pig ileum.

High affinity binding sites for LTC4 have been identified in various tissues, including guinea-pig ileal longitudinal muscle. More recently, it has been shown that LTC4 binds to non-receptor sites as well, particularly to glutathione transferases. In the present study, LTC4 and 9 chemically synthesized analogues, as well as the SRS-A antagonist FPL 55712 and S-decyl-glutathione, were tested for their ability to inhibit 3H-LTC4 binding in membranes from guinea-pig ileal longitudinal muscle and to affect the tone of the ileum in vitro. A significant correlation between binding and contractile activities was found for the LTC4 analogues and FPL 55712. However, S-decyl-glutathione, although possessing some affinity for LTC4 binding sites, was devoid of any effect on guinea-pig ileum tone at least up to 10(-5) M, thus indicating that these sites cannot be functional receptors, although they may represent other units involved in leukotriene action, e.g. uptake sites.

Animals↗
PubMed1989

[Neurologic manifestations of dissecting aneurysms of the aorta].

Dissecting aneurysm of the aorta keeps on being nowadays a diagnostic problem, although it is a well known entity. Dissecting aneurysms may be classified into type A, dissection involving the ascending aorta, and type B, dissection involving descending aorta. The frequency of neurologic manifestations oscillates from 18 to 30%. From the 133 cases of dissecting aneurysm attended at our hospital, 30 (22.5%) presented neurologic manifestations. Nine patients (30%) had symptoms of ischemic neuropathy; 13 (43.3%) presented symptoms compatible with spinal ischemia and 14 (46.7%) presented manifestations of brain ischemia, with involvement of supraaortic trunks proven at autopsy in eight cases. The neurologic complications of type A and B dissecting aneurysms were similar (28 and 26%); in up to 30% of patients, it was the initial symptom. In type A dissecting aneurysm, the most frequent neurologic manifestation was brain ischemia (57.1%) whereas ischemic neuropathy and spinal ischemia predominated in type B dissecting aneurysm. The overall mortality rate reached 76.7% (85.7% for type A and 55.5% for type B). The modality of treatment had no clear influence on the survival. In the presence of brain complications, the mortality was 100%.

Aged↗
PubMed1989

Hyposialylation of high-molecular-weight membrane glycoproteins parallels the loss of metastatic potential in wheat-germ agglutinin-resistant Friend leukemia cells.

From the highly metastatic in vivo-passaged Friend leukemia cells (FLC), WGA-resistant (WR) tumor cell variants were selected. These WR FLC had lost their capacity to metastasize when injected i.v. or s.c. into DBA/2 mice. We have characterized the plasma membrane glycoproteins of the different FLC types by: (i) metabolic labelling with (3H)-galactose; (ii) surface labelling with galactose oxidase-borohydride; (iii) direct binding of (125I)-lectins on glycoproteins separated by SDS-PAGE. The ensemble of these approaches showed that the 100- to 200-kDa glycoproteins of in vivo-passaged FLC and WR FLC exhibited a very similar distribution of the terminal galactose in their oligosaccharide moieties. In contrast, the expression of terminal sialic acid was reduced in WR FLC with respect to in vivo-passaged counterparts as appreciated by: (i) binding experiments with (125I)-WGA; (ii) cathodic shift of the 100- to 200-kDa glycoproteins in 2-dimensional electrophoresis studies, and (iii) thiobarbituric acid assay after FLC treatment with neuraminidase. Moreover, binding experiments with (125I)-LPHA, (125I)-ConA and (125I)-WGA (after Smith degradation) indicated that, in the 100- to 200-kDa region, virtually identical asparagine-linked tri- or tetra-antennary complex-type oligosaccharides were expressed in both cell types. We conclude that the sialylation of high-molecular-weight surface glycoproteins (particularly in the 150-kDa region) is strongly associated with the metastatic potential of FLC, especially to the liver.

Animals↗
PubMed1989

New isoxazole derivatives provided with antihypertensive activity.

A series of diazacycloalkane-quinazoline derivatives of isoxazoles were synthesized and tested in order to identify new potent and selective alpha 1-antagonists. A preliminary screening by using in vitro tests such as binding assay (3H-prazosin and 3H-rauwolscine displacement) and analysis of antagonistic activity in isolated rat aorta (norepinephrine-induced response) and in isolated rat vas deferens (clonidine-induced response) indicated that many of these compounds exhibited a good affinity and selectivity towards alpha 1-adrenergic receptors associated with potent pharmacological activity. In particular, a 3-bromo-5-isoxazolecarbonyl derivative, selected for further in vivo investigation, was provided with as high antihypertensive action as prazosin in spontaneously hypertensive rats (SHR) coupled to a shallow dose-response curve by oral route. Moreover, a higher ratio between oral antihypertensive doses in SHR and normotensive rats was found with respect to reference compound prazosin.

Animals↗
PubMed1989

Evidence of PAF-acether metabolic pathway activation in antigen challenge of upper respiratory airways.

Lyso-PAF-acether and PAF-acether (formerly platelet-activating factor) were detected in nasal secretions from patients with hay fever who underwent local antigen challenge. Lyso-PAF release was observed in 12 of 13 patients, with a maximum (p less than 0.001) 5 min after stimulation and a progressive decrease during the first hour. PAF was detected in the 5-min postchallenge nasal washings from two of 13 subjects. After HPLC, this mediator was found in four of seven postchallenge nasal washings submitted to this procedure, with a peak 5 min and 10 min after provocation. Histamine analysis revealed a significant (p less than 0.001) but time-limited (5 min) release in nasal secretion. The pattern of immunoreactive leukotriene C4 showed a maximal peak (p less than 0.01) 5 min after allergen provocation, with raised levels for 20 min. Nasal stimulation with nebulized saline solution or grass pollens in healthy subjects and in patients suffering from allergic rhinitis caused by Dermatophagoides pteronyssinus was followed by no local mediator release. These data indicate that, in addition to histamine and peptide-leukotrienes, lyso-PAF and PAF are released in nasal secretions after local antigen stimulation in patients with hay fever, with a preponderance of lyso-PAF response. On the basis of these results, it is conceivable that these ether-phospholipids may be involved in allergic inflammation of human nasal airways.

Adult↗
PubMed1989

Increase of alveolar pressure reduces systemic-to-pulmonary bronchial blood flow in humans.

We studied the effect of positive alveolar pressure (PA) on systemic to pulmonary bronchial blood flow, Q?? in humans. The Q?? was measured during total cardiopulmonary bypass as the volume of blood accumulating in the left heart. This blood was vented by gravity from the left heart via a cannula introduced in the right upper pulmonary vein and advanced to the lowest portion of the left heart. In group A (n = 10) the Qbr(s-p) was measured for 25 to 95 min with constant PA (4.0 +/- 0.2 cm H2O, mean +/- SE). In group B (n = 10) Qbr(s-p) was measured for 20 min with PA = 4.1 +/- 0.2 cm H2O and for a further 20 min with PA = 14.1 +/- 0.4 cm H2O. The Qbr(s-p) ranged between 0.32 and 2.76 percent of cardiac output (pump flow) and remained constant with time (group A). The increase of PA from 4.1 +/- 0.2 to 14.1 +/- 0.4 cm H2O reduced Qbr(s-p) by approximately 40 percent (p less than 0.01, group B). We conclude that positive PA reduces Qbr(s-p) during total cardiopulmonary bypass. Therefore, we advise using low PA during assisted ventilation to preserve bronchial blood flow.

Bronchi↗
PubMed1989

The pharmacology of leukotrienes in human airways: in vitro and in vivo studies.

Immunological challenge of human lung parenchyma causes formation of arachidonate metabolites: prostaglandin D2 (PGD2) (70% of the formed mediators), leukotrienes E4 (LTE4) (15%) and D4 (LTD4) (10%). Leukotriene B4 (LTB4) was barely detectable (2%). Inhibition of PGD2 formation by indomethacin (15 microM) was approximately 90%, but was not accompanied by redistribution of arachidonate metabolism towards sulphidopeptide leukotrienes, as postulated for aspirin-sensitive asthma. Specific binding sites for leukotrienes C4 (LTC4) have been identified in membrane preparations of human bronchi. Binding of 3H-LTC4 is rapid (1 min) and quickly reversible following addition of excess. The sites are specific for LTC4 and competition curves fitted a two-site model. Moreover, clinical studies on specific endobronchial challenge of patients allergic to Dermatophagoides pteronyssinus, revealed narrowing of bronchial diameter and oedema of the bronchial mucosa; these symptoms were accompanied by an increase of immunoreactive-LTC4 and PGD2 present in the bronchial lavage fluids.

Asthma↗