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Biomedical subjects

E Ortega

Publications and source records attributed to E Ortega.

At least 19 recordsLinked to original sources
PubMed1992

Antiflammins. Anti-inflammatory activity and effect on human phospholipase A2.

Two anti-inflammatory peptides (antiflammins) corresponding to a high amino acid similarity region between lipocortin I and uteroglobin were tested for their ability to inhibit purified human synovial fluid phospholipase A2 (HSF-PLA2). No inhibitory activity was observed, even at such high concentrations of peptides as 50 microM. When antiflammins were preincubated with the enzyme and/or the substrate, no HSF-PLA2 inhibition was detected. In vivo anti-inflammatory activity of these peptides was evaluated in several experimental models of inflammation induced by carrageenan, croton-oil, oxazolone and Naja naja naja venom phospholipase A2 (PLA2). In contrast to the in vitro results, anti-inflammatory activity was observed in all tests, except when inflammation was induced by snake venom PLA2. Taken together, our results do not support the hypothesis that the in vivo anti-inflammatory effect of antiflammins is directly related to inhibition of PLA2 activity.

Animals↗
PubMed1992

Stimulation of the phagocytic function in guinea pig peritoneal macrophages by physical activity stress.

A study was made of all the different stages of the phagocytic function in peritoneal macrophages from male guinea pigs [3 (SD 1) months old] before, immediately after, and 24 h after being subjected to stress from physical activity (swimming until exhaustion). The early (10 min) and late (40 min) adherence to tissue substrates, chemotaxis, attachment and phagocytosis of Candida albicans, ingestion of inert particles (latex beads), and basal oxidative metabolism [measured by nitroblue tetrazolium (NBT) reduction] were significantly stimulated by the physical activity. After 24 h, late adherence, attachment capacities, and basal oxidative metabolism returned to basal values, whereas early adherence, chemotaxis, phagocytosis of cells and inert particles, and microbicidal capacity (production of superoxide anion measured by NBT reduction in presence of ingested material) remained significantly increased. The stress produced by physical activity, reflected in increased serum corticosterone values, led to a global stimulation of the phagocytic function.

Animals↗
PubMed1992

Effect of physical activity stress on the phagocytic process of peritoneal macrophages from old guinea pigs.

The different stages of the phagocytic function in peritoneal macrophages from old guinea pigs (27 +/- 3-months-old) were studied before, immediately after and 24 h after being subjected to physical activity stress (swimming until exhaustion) which raised the blood levels of corticosterone. The phagocytosis of opsonized Candida albicans was stimulated immediately after physical activity. No modifications in adherence, chemotaxis, ingestion of inert particles, or microbicide capacity, measured by nitroblue tetrazolium (NBT) reduction, were found. At 24 h, when no stress could be shown by corticosterone analysis, the phagocytosis of opsonized C. albicans remained stimulated and chemotaxis was increased while ingestion of inert particles and microbicide capacity remained unchanged. The adherence, however, was at a smaller level. No correlations were found between the corticosterone levels and the status of the phagocytic process of peritoneal macrophages.

Aging↗
PubMed1992

Phagocytosis of latex beads by alveolar macrophages from mice exposed to cigarette smoke.

Cigarette smoking is known to alter the numerical presence and function of alveolar macrophages. It has been speculated that these cigarette-smoke-induced alterations contribute to the depressed pulmonary defence mechanism commonly demonstrated in smokers. Studies of the phagocytic and bactericidal activities of alveolar macrophages from smokers and non-smokers have yielded conflicting results. The purpose of this study was to investigate the phagocytic capacity of alveolar macrophages from mice exposed to cigarette smoke in relation to the ability to ingest inert particles (latex beads). Measurements were made before (basal values), immediately after, and 1, 12 or 24 h after exposure. Significant decreases were observed in the number of latex beads ingested by 100 macrophages (phagocytic index) and in the phagocytic efficiency for ingesting latex (mean number of latex beads ingested per activated macrophages) immediately after and 1 h after exposure, and in the number of activated macrophages (those with phagocytic activity) immediately after exposure.

Animals↗
PubMed1992

PLA2-induced oedema in rat skin and histamine release in rat mast cells. Evidence for involvement of lysophospholipids in the mechanism of action.

Injection of phospholipase A2 (PLA2) in the rat skin produced a significant rise in oedema, which was inhibited by the simultaneous coinjection of aristolochic acid (100 micrograms), mepacrine (100 micrograms) and p-bromophenacyl bromide (10 micrograms). Indomethacin, nordihydroguaiaretic acid and WEB 2086 were without inhibitory effect on this model, whereas dexamethasone (5 mg/kg, p.o.) and coinjection of chlorpheniramine (20 micrograms) inhibited the oedema formation by more than 60%. Dose-dependent histamine release by rat peritoneal cells was induced by PLA2 and by lysophosphatidylserine and this effect could be antagonized by aristolochic acid and mepacrine. Apomorphine, previously reported to be an antagonist at lysophospholipid receptors, was able to inhibit the histamine release by mast cells as well as the oedema formation in rat skin. Taken all together, these results suggest that lysophospholipids, produced by the action of PLA2, are the mediators for the histamine release in rat peritoneal cells and could play an important role in the early oedema development in rat skin after PLA2 administration.

Animals↗
PubMed1992

Androgenic status in cyclic and postmenopausal women: a comparison between smokers and nonsmokers.

Serum total testosterone (T), free testosterone (fT) sex hormone binding globulin (SHBG), androstenedione (A) and 3 alpha androstanediol glucuronide (3 alpha-diol G) levels as well as serum free androgen index (FAI), fT/T and 3 alpha-diol G/T ratios were measured in premenopausal and cyclic women, grouped according to sexual status and smoking status. Our results showed that serum T, fT, SHBG, A and 3 alpha-diol G levels were lower in cyclic women in the follicular than in the luteal phase of the ovarian cycle, although the differences between these values were not significant. Postmenopausal women had significantly lower values of T, fT, A 3 alpha-diol G, FAI and 3 alpha diolG/T but not SHBG and fT/T than cyclic women. When we compared women smokers and nonsmokers, women smokers had serum levels of T, fT, SHBG, 3 alpha-diol G, and values of FAI, fT/T and 3 alpha-diol G/T, similar to those in nonsmokers. Serum A levels were higher in women smokers than in nonsmokers, although the difference was significant only in postmenopausal women.

Androgens↗
PubMed1992

[Treatment and prevention of the ovarian hyperstimulation syndrome].

Frequency and features of ovarian hyperstimulation syndrome (OHS) were reviewed in 41 women stimulated with human menopausal gonadotropin (HMG) during 130 cycles. There were 7 cases of OHS, since 17% of patients and 5.3% of cycles were affected; 3 cases were mild, 2 moderate and 2 severe. Of these 41 women, 21 pregnancies occurred (51%) and 19 newborns were healthy. The patients with OHS received 1060 +/- 235 (X +/- DE) UI of HMG and there was not a significative difference with the amount of HMG units in remaining subjects. Symptoms began 3-6 days after human chorionic gonadotropin (HCG) administration. Women with mild OHS were treated as out patients with bed rest and 100 mg indomethacin in suppositories two times a day. Moderate and severe OHS were hospitalized with bed rest; careful monitoring of fluid intake and output, weight and abdominal perimeter daily, as well as vital signs were withdrawn. Patients with severe OHS were treated in the intensive care unit for detection and management of complications. One patient was submitted to laparotomy because of a probably ovarian rupture, but it was discarded in the surgery. OHS remained between 6 and 8 days. Patients with OHS presented 3 pregnancies, 2 were twins and the other was ectopic. Emphasis was made in the prophylactic measures to avoid the OHS.

Adult↗
PubMed1992

[Ovulation induction with gonadotropins aided by cervix mucus analysis and echography].

Induction of ovulation was performed in 148 cycles using human menopausal gonadotropins (HMG) in 52 patients, seven with hypothalamic-pituitary failure and 45 suffering dysfunction at this level. Several induction schemes were used beginning on the second day of the cycle, until one or more follicles larger than 14 mm were found, to administrate 10,000 UI of human chorionic gonadotropin (HCG). Clinical valuation of cervical mucus and ultrasound of the ovaries to assess follicular development were done, from day eight of the cycle. Twenty five pregnancies resulted in 23 patients (44%), three in patients with failure and 22 in the dysfunction group. A total of 19 healthy babies were taken home, however three neonatal deaths, four miscarriages and one ectopic pregnancy occurred. Multiple gestation was present in three patients (12%), one was quadruplet, one triplet and one twin. The ovarian hyperstimulation syndrome (OHS) was detected in seven patients (13.4%), three were mild, two moderate and two severe; two cases of OHS had multiple pregnancies. Although induction of ovulation with HMG in patients with anovulation is a complex procedure requiring strict clinical vigilance and advanced technological resources, in this clinical study it was possible to obtain similar results to other series, using high resolution ultrasound only, without daily measurements of hormones.

Adult↗
PubMed1991

Rotational dynamics of the Fc epsilon receptor on mast cells monitored by specific monoclonal antibodies and IgE.

The rotational motions of the type I receptor for the Fc epsilon domains (Fc epsilon RI) present on mast cells were investigated by measuring the phosphorescence emission and anisotropy decay kinetics of erythrosin (Er) covalently bound to several Fc epsilon RI-specific macromolecular ligands. The latter consisted of three murine monoclonal antibodies (IgG class) raised against the Fc epsilon RI of rat mast cells (RBL-2H3 line), their Fab fragments, and a murine monoclonal IgE. Different anisotropy decay patterns were observed for the three monovalent Er-Fab fragments bound to the Fc epsilon RI, reflecting the rotational motion of the Fe epsilon RI reported by each specific macromolecular probe bound to its particular epitope. Internal motions of the tethered Er-labeled ligands may also contribute to the observed anisotropy decay, particularly in the case of cell-bound IgE. The results corroborate an earlier study with rat Er-IgE in which the Fc epsilon RI-IgE complex was shown to be mobile throughout the temperature range examined (5-37 degrees C). The anisotropy decays of the three Er-labeled, Fc epsilon RI-specific intact mAbs bound to cells also differed markedly. Whereas the decay curves of one mAb (H10) were characterized by temperature-dependent positive amplitudes and rather short rotational correlation times, the decay of a second mAb (J17) showed complex qualitative variations with temperature, and in the case of the third antibody (F4), there was no apparent decay of anisotropy over the time and temperature ranges examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Kinetics of ligand binding to the type 1 Fc epsilon receptor on mast cells.

Rates of association and dissociation of several specific monovalent ligands to and from the type I Fc epsilon receptor (Fc epsilon RI) were measured on live mucosal type mast cells of the rat line RBL-2H3. The ligands employed were a monoclonal murine IgE and Fab fragments prepared from three different, Fc epsilon RI-specific monoclonal IgG class antibodies. These monoclonals (designated H10, J17, and F4) were shown previously to trigger mediator secretion by RBL-2H3 mast cells upon binding to and dimerization of the Fc epsilon RI. Analysis of the kinetics shows that the minimal mechanism to which all data can be fitted involves two consecutive steps: namely, ligand binding to a low-affinity state of the receptor, followed by a conformational transition into a second, higher affinity state h of the receptor-ligand complex. These results resolve the recently noted discrepancy between the affinity of IgE binding to the Fc epsilon RI as determined by means of binding equilibrium measurements [Ortega et al. (1988) EMBO J. 7, 4101] and the respective parameter derived from the ratio of the rate constant of rat IgE dissociation and the initial rate of rat IgE association [Wank et al. (1983) Biochemistry 22, 954]. The probability of undergoing the conformational transition differs for the four different Fc epsilon RI-ligand complexes: while binding of Fab-H10 and IgE favors the h state, binding of Fab-J17 and Fab-F4 preferentially maintains the low-affinity 1 state (at 25 degrees C). The temperature dependence of the ligand interaction kinetics with the Fc epsilon RI shows that the activation barrier for ligand association is determined by positive enthalpic and entropic contributions. The activation barrier of the 1----h transition, however, has negative enthalpic contributions counteracted by a decrease in activation entropy. The h----1 transition encounters a barrier that is predominantly entropic and similar for all ligands employed, thus suggesting that the Fc epsilon RI undergoes a similar conformational transition upon binding any of the ligands.

Animals↗
PubMed1991

Possible interactions between the Fc epsilon receptor and a novel mast cell function-associated antigen.

We have recently described a monoclonal antibody, mAb G63, which identifies a novel membrane component of mast cells. This antigen is a glycoprotein with an apparent molecular mass of 28-40 kd, and is present on the surface of rat mucosal and serosal mast cells. Its density on cells of the mucosal mast cell line RBL-2H3 is 1 - 2 x 10(4) copies per cell. Crosslinking of this membrane protein by the intact mAb G63 results in a pronounced inhibition of the Fc epsilon RI-mediated secretion of RBL-2H3 cells. Here we show that crosslinking this novel membrane component inhibits biochemical processes initiated by Fc epsilon RI aggregation, such as the hydrolysis of phosphatidylinositides, the influx of Ca2+ ions, and the synthesis and release of de novo formed inflammatory mediators. Furthermore, by fluorescence microscopy, we show that crosslinking of Fc epsilon RI-IgE complexes by multivalent antigen results in redistribution of the membrane component recognized by G63, leading to its co-localization with the aggregated Fc epsilon RI. This localization is inhibited by NaN3, but not by colchicine or cytochalasin D. Fc epsilon RI crosslinking also promotes internalization of this novel membrane component. Taken together these data suggest that the mast cell membrane component recognized by mAb G63 is involved in the Fc epsilon RI-mediated stimulation of these cells, and thus can be considered a mast cell function-associated antigen (MAFA).

Animals↗
PubMed1990

Activity of the hypothalamo-pituitary ovarian axis in hypothyroid rats with or without triiodothyronine replacement.

The hypothalamic pituitary ovarian axis in adult female rats with 131-I induced hypothyroidism was studied before and after triiodothyronine (T3) replacement. Forty days after 131-I, hypothyroid (H) rats showed irregular cycles with predominantly diestrous vaginal smears, atrophied and underweight ovaries, and decreased serum T3, T4, LH and estradiol (E2). T3 replacement restored normal cycles and ovary weight and increased serum E2 levels above control values, while LH levels remained below the limit of detection of the RIA. The GnRH stimulation test performed on the day that the rats exhibited diestrous vaginal smears elicited a greater increase in FSH than in LH in H rats and a greater increase in LH than in FSH in both H-T3 treated and control rats. The data suggest that the lack of thyroid hormones in adult female rats seems to produce a reversion of sexual hormones to a prepubertal pattern, while T3 treatment restored normal estrous cycles and ovarian function.

Animals↗
PubMed1990

Changes in the phagocytic function of peritoneal macrophages from old mice after strenuous physical exercise.

The effect of acute physical exercise (swimming until exhaustion) on the phagocytic function of peritoneal macrophages from old adult BALB/c mice (55 +/- 5 weeks old) was studied. Adherence capacity of macrophages to substrate, spontaneous mobility and chemotaxis as well as digestion capacity measured by nitroblue tetrazolium (NBT) reduction in presence of ingested material (latex beads) were not modified with exercise. Adherence to nylon fiber, opsonization and ingestion of Candida albicans (either spontaneous or in presence of serum), ingestion of latex particles as well as nitroblue tetrazolium (NBT) reduction in absence of ingested material (oxidative metabolism measure) were increased in respect to controls with statistically significant differences (P less than 0.001) in peritoneal macrophages after the exercise.

Aging↗
PubMed1990

A glycolipid-specific monoclonal antibody modulates Fc epsilon receptor stimulation of mast cells.

In an effort to identify membrane components participating in coupling stimulus to secretion in mast cells, monoclonal antibodies were produced from spleen cells of mice immunized with plasma membranes isolated from rat mast cells of the RBL-2H3 line. The resultant mAbs were screened by their capacity to modulate the secretory response of these cells to crosslinking of their type 1 Fc epsilon receptor (Fc epsilon RI). Following this scheme, we obtained a hybridoma designated B17, which secretes an IgM-class mAb (B17) that binds to and modulates secretion from RBL-2H3 cells. By immunoblotting, B17 was shown to bind to a membrane component of low molecular weight, later identified as a glycolipid. While B17 partially inhibits IgE binding to RBL-2H3 cells, no noticeable inhibition of B17 binding by IgE was observed. mAb B17 does not cause any secretory response on its own, and its modulatory effect on Fc epsilon RI-mediated secretion is bimodal: it either enhances or inhibits secretion, depending on the B17 dose and also on the nature and dose of the agent used for crosslinking the Fc epsilon RI. When secretion was induced by IgE and suboptimal or optimal doses of multivalent antigen, B17 (2-80 nM) caused an increase in secretion. However, higher doses of B17 (greater than 150 nM) inhibited secretion. Secretion induced by supraoptimal doses of antigen, or by the Fc epsilon RI-specific mAb F4 was inhibited by B17 at all the dose range tested (2-200 nM). In contrast, B17 had no effect on secretion induced by Ca2+ ionophores. These results demonstrate that Fc epsilon RI function is modulated by a mAb binding to a membrane glycolipid.

Animals↗
PubMed1989

Mast cell stimulation by monoclonal antibodies specific for the Fc epsilon receptor yields distinct responses of arachidonic acid and leukotriene C4 secretion.

The release of arachidonic acid ([3H]AA) and leukotriene C4 (LTC4) from the rat mucosal mast cells of the RBL-2H3 line stimulated by Fc epsilon receptor-specific monoclonal antibodies (mAb), by IgE and multivalent antigen, or by Ca2+ ionophores, was investigated. In parallel, secretion of the granular enzyme beta-hexosaminidase was also assayed. The release of [3H]AA and LTC4 in response to stimulation by three Fc epsilon RI-specific mAb shows similar quantitative differences to those observed for the secretion of granule-stored mediators. The mAb F4 induced a substantial release of both [3H]AA and LTC4, which is as high as that induced by IgE and multivalent antigen. mAb J17 and H10 were found to induce an insignificant release of [3H]AA, but while J17 did induce release of LTC4, H10 failed to induce it, even though both J17 and H10 caused substantial release of beta-hexosaminidase. Ca2+ ionophores were found to be relatively more effective in inducing release of [3H]AA and LTC4 than in causing the secretion of granular mediators, as compared to cell stimulation by Fc epsilon RI aggregation. These results illustrate that the cell responses of degranulation and de novo synthesis and release of mediators have different sensitivities to stimulation by (a) configurationally distinct Fc epsilon RI dimers, (b) Fc epsilon RI aggregates induced by IgE and multivalent antigen, and (c) Ca2+ ionophores.

Animals↗
PubMed1988

Possible orientational constraints determine secretory signals induced by aggregation of IgE receptors on mast cells.

Three biologically active monoclonal antibodies (mAbs) specific for the monovalent, high-affinity membrane receptor for IgE (Fc epsilon R) were employed in analysing the secretory response of mast cells of the RBL-2H3 line to crosslinking of their Fc epsilon R. All three mAbs (designated F4, H10 and J17) compete with each other and with IgE for binding to the Fc epsilon R. Their stoichiometry of binding is 1 Fab:1 Fc epsilon R, hence, the intact mAbs can aggregate the Fc epsilon Rs to dimers only. Since all three mAbs induce secretion, we conclude that Fc epsilon R dimers constitute a sufficient 'signal element' for secretion of mediators for RBL-2H3 cells. The secretory dose-response of the cells to these three mAbs are, however, markedly different: F4 caused rather high secretion, reaching almost 80% of the cells' content, while J17 and H10 induced release of only 30-40% mediators content. Both the intrinsic affinities and equilibrium constants for the receptor dimerization were derived from analysis of binding data of the Fab fragments and intact mAbs. These parameters were used to compute the extent of Fc epsilon R dimerization caused by each of the antibodies. However, the different secretory responses to the three mAbs could not be rationalized simply in terms of the extent of Fc epsilon R dimerization which they produce. This suggests that it is not only the number of crosslinked Fc epsilon Rs which determines the magnitude of secretion-causing signal, but rather other constraints imposed by each individual mAb are also important.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The normal vascularization of the intradural filum terminale in man.

The arterial and venous blood-supply of the intradural filum terminale was studied microscopically in 18 fresh cadavers after removing the dorsolumbar spinal cord in one piece, with the roots and the filum in their dural sheath. The arteries were examined after manual injection of the artery of the lumbar enlargement, while study of the veins was made without injection since their bluish-black color made them easily identifiable. After gross examination, each specimen was fixed and then sectioned at 12 different levels from the medullary conus to the bottom of the dural sac for histologic study. The distribution of the vascularization of the filum terminale appeared constant. A single artery, the artery of the filum, arises from the termination of the anterior spinal axis, either by trifurcation or from the proximal part of one of the 2 branches of the anastomotic ansa of the conus. The artery travels in front of the filum, with rapidly diminishing caliber; rarely, it can be followed into the sacral canal. The vein of the filum travels in front of that structure but behind the artery, as in the cord; its caliber is uniform but varies from subject to subject. It traverses the dura below and is continuous with the anterior spinal vein above. No vessels were found on the dorsal aspect of the filum. While the artery of the filum is of a caliber proportional to that of the filum and appears to be a nutrient vessel, the vein has a caliber unrelated to that of the filum and appears rather as an intradural drainage route continuous with the anterior spinal vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗