Search PubMed⌕ Search

Biomedical subjects

E Ortega

Publications and source records attributed to E Ortega.

At least 73 records · Page 4Linked to original sources

Modulation of adherence and chemotaxis of macrophages by norepinephrine. Influence of ageing.

We evaluated the in vitro effect of norepinephrine (NE), over the range of concentrations between 10(-12) M and 10(-3) M, on adherence (to plastic surfaces) and chemotaxis (in a Boyden chamber) of peritoneal macrophages from BALB/c mice of different ages: young (12 weeks), adult (22 weeks), mature (48 weeks) and old (72 weeks). Increased adherence was induced by 10(-12) M of NE in macrophages from young, adult, mature and old mice. Also, 10(-9) M stimulated adherence in old animals, 10(-5) M in mature mice, and 10(-3) M in both young and old mices. With respect to chemotaxis, the low concentration of NE (10(-12) M) was stimulatory only in young and adult animals, higher concentrations (10(-5) M and 10(-7) M) were inhibitory for macrophages from mature and old animals, and the highest concentration of NE (10(-3) M) stimulated this capacity of macrophages only in young and mature animals. The conclusion is that while the mobility of macrophages to the focus of infection (i.e. chemotaxis) is stimulated by low concentrations of NE (10(-12) M) only in young-adult animals, this neurotransmitter induces a decline in this capacity in mature and old mice at high concentrations (10(-5) M-10(-7) M). Also, macrophages from old animals have lost the capacity to respond to pharmacological (10(-3) M) concentrations of NE. The lower capacity of response to NE by macrophages from old animals possibly contributes to immunosenescence.

Aging↗

Isolation and characterization of a major allergen from the fish parasite Anisakis simplex.

BACKGROUND: Ingestion of raw or undercooked fish can lead to infection of human subjects by the fish parasite Anisakis simplex, a disease known as anisakiasis or anisakidosis. Patients sensitized to this fish parasite show high levels of total and specific IgE. Cross-reactions seem to explain the fact that specific IgE antibodies are also found in a high number of normal subjects, as reported in other parasitoses. OBJECTIVE: We sought to purify and characterize a major IgE-binding protein from the parasite. METHODS: A protein was purified from the crude parasite extract by means of ethanol precipitation and reversed-phase HPLC. Its clinical relevance was tested on 20 parasite-positive sera by using IgE and IgG4 immunoblotting. A monospecific human serum was used to study its localization in the parasite body. RESULTS: A 24-kd protein was purified, to which only 45% of the sera had specific IgG4, but 85% of sera had specific IgE. The protein was present only in the excretory gland, as shown by immunohistochemistry. N-terminal amino acid sequence (17 residues) showed no homology to previously described proteins. CONCLUSION: A simplex contains a potent allergen in the excretory gland. This major parasite allergen, named Ani s 1, could have important clinical relevance, as shown by the high number of positive sera in the specific IgE immunoblotting.

Allergens↗

Negative regulation of FcepsilonRI signaling by FcgammaRII costimulation in human blood basophils.

BACKGROUND: Signaling through the antigen receptors of human B and T cells and the high-affinity IgE receptor FcepsilonRI of rodent mast cells is decreased by cross-linking these receptors to the low-affinity IgG receptor FcgammaRII. The inhibition is thought to involve the tyrosine phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the FcgammaRIIB cytoplasmic tail, creating binding sites for SH2-containing protein (Src homology domain containing protein tyrosine phosphatase 1 and 2 [SHP-1, SHP-2]) and/or lipid (SH2 domain-containing polyphosphatidyl-inositol 5-phosphatase) phosphatases that oppose activating signals from the costimulated antigen receptors. OBJECTIVE: In human basophils and mast cells FcepsilonRI signaling generates mediators and cytokines responsible for allergic inflammation. We proposed to determine whether FcepsilonRI signaling is inhibited by FcgammaRII costimulation in human basophils and to explore the underlying mechanism as an approach to improving the treatment of allergic inflammation. METHODS: FcgammaR expression on human basophils was examined using flow cytometry and RT-PCR analysis. FcgammaRII/FcepsilonRI costimulation was typically accomplished by priming cells with anti-dinitrophenol (DNP) IgE and anti-DNP IgG and stimulating with DNP-BSA. Phosphatases were identified by Western blotting, and their partitioning between membrane and cytosol was determined by cell fractionation. Biotinylated synthetic peptides and phosphopeptides corresponding to the FcgammaRIIB ITIM sequence were used for adsorption assays. RESULTS: We report that peripheral blood basophils express FcgammaRII (in both the ITIM-containing FcgammaRIIB and the immunoreceptor tyrosine-based activation motif-containing FcgammaRIIA forms) and that costimulating FcgammaRII and FcepsilonRI inhibits basophil FcepsilonRI-mediated histamine release, IL-4 production, and Ca(2+) mobilization. The inhibition of basophil FcepsilonRI signaling by FcgammaRII/FcepsilonRI costimulation is linked to a significant decrease in Syk tyrosine phosphorylation. Human basophils express all 3 SH2-containing phosphatases. CONCLUSIONS: Evidence that FcgammaRII/FcepsilonRI costimulation induces SHP-1 translocation from the cytosolic to membrane fractions of basophils and that biotinylated synthetic peptides corresponding to the phosphorylated FcgammaRIIB ITIM sequence specifically recruit SHP-1 from basophil lysates particularly implicates this protein phosphatase in the negative regulation of FcepsilonRI signaling by costimulated FcgammaRII.

Basophils↗

Determination of natural resistance of mice fed dietary lipids to experimental infection induced by Listeria monocytogenes.

Current understanding based on the effect of dietary lipid manipulation upon immune system function indicates that fatty acids are involved in the modulation of the immune response through different and complex pathways. Reduction of several immune parameters by fatty acid action may be applied in the treatment of diseases characterised by an overactivation of the immune system. As a consequence, a reduction of host resistance against infectious agents has been reported in animals fed dietary lipids. The present study confirms the action of dietary lipids on the survival of mice infected with the pathogenic bacterium Listeria monocytogenes. A significant increase in peritoneal cells from mice fed a hydrogenated coconut oil diet was found, while a significant reduction of bacterial recovery from spleens of these mice was observed in this group. In addition, both eicosanoid and phospholipase inhibitors did not promote any modification of lymphocyte proliferation from mice fed olive oil or fish oil.

Animals↗

Enhanced resistance to experimental systemic candidiasis in tilorone-treated mice.

Candida albicans is an increasingly important opportunistic fungal pathogen in immunocompromised patients. Natural killer (NK) cells constitute an important immune effector mechanism and are involved in the response to different pathological disorders. We wished to determine if this immune mechanism is involved in the specific response to C. albicans. Tilorone hydrochloride and related compounds have been described to display antiviral and antitumoral activity, as well as to enhance NK cell activity. In this study, we show the antimicrobial activity of different tilorone analogues and the enhanced resistance of tilorone-treated mice in experimental systemic candidiasis. We also present data suggesting that there is a correlation between NK cell activation and the resistance to experimental systemic candidiasis. Thus, it seems that the immunosurveillance of metastatic spread and the infection by C. albicans share some immune effector mechanisms, in particular activation of NK cells.

Animals↗

Effect of estrogen-progestin replacement therapy on plasma lipids and lipoproteins in postmenopausal women.

Serum levels of cholesterol (Chol), triglycerides (TG), low-density lipoprotein cholesterol (LDL) high-density lipoprotein cholesterol (HDL), both apolipoproteins A1 and B (Apo A1, Apo B), follicle-stimulating hormone (FSH) luteinizing hormone (LH), estradiol (E2), progesterone (P), testosterone (T) and steroid hormone binding globulin (SHBG) were measured in postmenopausal women, before and after four different estrogen-progestin replacement therapies. Each woman was her own control to avoid genetic or socioeconomic differences. Our results showed that serum E2 and TG significantly increased and serum FSH, LH, LDH, Apo B, and Chol significantly decreased after all treatments. Serum P and T did not significantly change after any of the treatments. HDL, Apo A1 and SHBG significantly increased in the groups treated with medroxiprogesterone acetate (MPA) but not in the group treated with Norgestrel. We conclude that estrogen-progestin replacement therapy in postmenopausal women leads to profound and beneficial changes in plasma lipids and lipoproteins and that treatments with cyclic or continuous MPA could provide greater protection against coronary heart disease (CHD).

Apolipoprotein A-I↗

Ageing modulates some aspects of the non-specific immune response of murine macrophages and lymphocytes.

The deterioration of the immune system with ageing, which leads to an increased morbidity and mortality from infections, appears to be related to decreases in specific lymphocyte functions. However, the alteration of non-specific immunity is a more controversial subject. Our purpose was to investigate the age-related changes of different functions of the non-specific immune response in peritoneal macrophages (adherence to tissues, mobility directed to a chemical gradient from an infectious focus or chemotaxis, phagocytosis of foreign agents and destruction of these agents by superoxide anion production) and in lymphocytes (adherence and chemotaxis) from peritoneum, axillary lymph nodes, spleen and thymus. We used young (12 weeks), adult (22 weeks), mature (48 weeks) and old (72 weeks) female BALB/c mice. The adherence capacity of macrophages and lymphocytes was greater in adult and old mice than in young animals. The chemotaxis of macrophages showed higher values in cells from young mice than in those from adult mice, increasing again in macrophages from mature and old animals. A similar behaviour was shown by phagocytosis, which reached its highest values in old animals. Anion superoxide production increased with age and again the highest values were obtained in the oldest mice. Conversely, chemotaxis of lymphocytes was higher in the adult and mature animals than in the young and old animals. We conclude that, although there is a decrease in lymphocyte chemotaxis in old animals, the non-specific immune response of macrophages instead of decreasing, may increase in aged mice with respect to the values seen in adult mice.

Aging↗

The development of brain sex differences: a multisignaling process.

In order to account for the development of sex differences in the brain, we took, as an integrative model, the vomeronasal pathway, which is involved in the control of reproductive physiology and behavior. The fact that brain sex differences take place in complex neural networks will help to develop a motivational theory of sex differences in reproductive behaviors. We also address the classic genomic actions in which three agents (the hormone, the intracellular receptor, and the transcription function) play an important role in brain differentiation, but we also point out refinements that such a theory requires if we want to account of the existence of two morphological patterns of sex differences in the brain, one in which males show greater morphological measures (neuron numbers and/or volume) than females and the opposite. Moreover, we also consider very important processes closely related to neuronal afferent input and membrane excitability for the developing of sex differences. Neurotransmission associated to metabotropic and ionotropic receptors, neurotrophic factors, neuroactive steroids that alter membrane excitability, cross-talk (and/or by-pass) phenomena, and second messenger pathways appear to be involved in the development of brain sex differences. The sexual differentiation of the brain and reproductive behavior is regarded as a cellular multisignaling process.

Animals↗

Suppression of both basal and antigen-induced lipid peroxidation in ring dove heterophils by melatonin.

There have been several findings recently concerning melatonin as a free radical scavenger and general antioxidant. For instance, in bird heterophils we found that 100 microM of melatonin decreases superoxide anion levels and modulates superoxide dismutase activity. This paper sought to study the effect of melatonin upon induced oxidative damage in heterophils of the ring dove (Streptopelia risoria). The concentration of malonaldehyde (MDA) as an index of induced oxidative damage to lipid membranes was tested by colorimetric assay. A heterophil suspension was co-incubated with and without inert particles (latex beads) as material to be phagocytosed, both alone and in combination with 100 microM of melatonin. Measurements were made at the basal time (0 min), as well as at 15, 30, 45, and 60 min. Protein concentrations were determined by a standardized method using bovine serum albumin as standard. Results are expressed as nmol MDA/mg prot. Melatonin clearly reduced the production of MDA, an index of lipid peroxidation. It also annulled the enhancement of MDA levels produced by latex beads. Both effects were observed at all the times studied. In conclusion, our findings again show that the neurohormone melatonin could be useful as an effective pharmacological antioxidant.

Animals↗

Low affinity Fc gamma receptors on murine macrophages: mitogen-activated protein kinase activation and AP-1 DNA binding activity.

Mouse macrophage cell lines such as J774 express Fc receptors for IgG2a immune complexes, which upon binding of the proper ligand, trigger several signal transduction pathways. A surface to nucleus signaling through these receptors has been demonstrated. We describe here the activation of the mitogen-activated protein kinase (MAPK) and an increase in the binding of the activator protein 1 (AP-1) to DNA upon receptor stimulation. The described effects are only partially blocked by inhibitors of the Ca2+/diacylglycerol-dependent protein kinase (PKC), suggesting that differential signaling pathways are activated upon receptor cross-linking and that they converge at or above the MAPK level. These results pave the way to our understanding of Fc gammaR cross-linking induced gene expression regulation.

Animals↗

Lyn dissociation from phosphorylated Fc epsilon RI subunits: a new regulatory step in the Fc epsilon RI signaling cascade revealed by studies of Fc epsilon RI dimer signaling activity.

Cross-linking the heterotrimeric (alpha beta gamma 2) IgE receptor, Fc epsilon RI, of mast cells activates two tyrosine kinases: Lyn, which phosphorylates beta and gamma subunit immunoreceptor tyrosine-based activation motifs, and Syk, which binds gamma-phospho-immunoreceptor tyrosine-based activation motifs and initiates cellular responses. We studied three Fc epsilon RI-dimerizing mAbs that maintain similar dispersed distributions over the surface of RBL-2H3 mast cells but elicit very different signaling responses. Specifically, mAb H10 receptor dimers induce very little inositol 1,4,5-trisphosphate synthesis, Ca2+ mobilization, secretion, spreading, ruffling, and actin plaque assembly, whereas dimers generated with the other anti-Fc epsilon RI mAbs induce responses that are only modestly lower than that to multivalent Ag. H10 receptor dimers activate Lyn and support Fc epsilon RI beta and gamma subunit phosphorylation but are poor Syk activators compared with Ag and the other anti-Fc epsilon RI mAbs. H10 receptor dimers have two other distinguishing features. First, they induce stable complexes between activated Lyn and receptor subunits. Second, the predominant Lyn-binding phospho-beta isoform found in mAb H10-treated cells is a less tyrosine phosphorylated, more electrophoretically mobile species than the predominant isoform in Ag-treated cells that does not coprecipitate with Lyn. These studies implicate Lyn dissociation from highly phosphorylated receptor subunits as a new regulatory step in the Fc epsilon RI signaling cascade required for Syk activation and signal progression.

Animals↗

Chlorambucil-induced inappropriate antidiuresis in a man with chronic lymphocytic leukemia.

The syndrome of inappropriate antidiuretic hormone (SIADH) has been described in patients suffering from leukemia or lymphoma involving the central nervous system. Several alkylating agents have also been associated with this syndrome. We describe a patient with chronic lymphocytic leukemia, without evidence of central nervous system involvement, who suffered from SIADH presumably caused by small doses of chlorambucil.

Antineoplastic Agents, Alkylating↗

Evaluation of cytokine production and phagocytic activity in mice infected with Campylobacter jejuni.

The effect of several Campylobacter jejuni strains on the immune response was analyzed in mice after intraperitoneal inoculation with 10(10) colony forming units (CFU). Three C. jejuni strains were assayed: CCUG 6968 (enterotoxigenic), CCUG 7580 (enterotoxigenic), and CCUG 7440 (non-enterotoxigenic). These C. jejuni strains induced a peritoneal inflammatory response and an important increase in the peritoneal phagocyte oxidative activity measured by chemiluminescence assay, as well as an increase in the number of peritoneal cells. Both interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) production by peritoneal cells were not modified. However, C. jejuni 7440 caused a statistically significant increase in TNFalpha production. These results have demonstrated that different strains of C. jejuni induce an increase of the inflammatory response without a significant cytokine release. However, these infectious microorganisms may be eliminated efficiently by murine macrophages after phagocytosis.

Animals↗

Effects of aztreonam on natural immunity in mice.

The influence of the dose and the duration of treatment with aztreonam, a monocyclic beta-lactam antibiotic, on the natural immune response of mice has been investigated. The results show the effects induced by the antibiotic on several immune parameters were affected by the duration of treatment. Thus, treatment with 28 mg/kg per day of aztreonam over 14 days increased every immune parameter tested, while treatment with 57 mg/kg per day of aztreonam for 7 days only enhanced the natural killer (NK) activity of splenocytes. Since aztreonam does not apparently impair the innate immune response, it might be a suitable therapy for the treatment of patients who are immunosuppressed.

Animals↗

Enhanced chemotaxis of macrophages by strenuous exercise in trained mice: thyroid hormones as possible mediators.

Exercise modulates the macrophage activity via 'stress hormones'. Three experiments were performed. (1) The effect of strenuous exercise performed by trained mice on macrophage chemotactic capacity was evaluated; (2) peritoneal macrophages from control mice were incubated with plasma from exercised mice or control mice and the differences in chemotaxis were measured; (3) changes in plasma T3 and T4 levels after exercise were measured, and the effect of incubation with the post-exercise levels of plasma T3 and T4 on chemotaxis was then studied in vitro. A 10(4)-fold higher concentration of each hormone was also evaluated. Exercise provoked an increase in chemotaxis (104 +/- 35 vs. 47 +/- 11 in controls). Incubation with plasma from exercised mice led to an increased level of chemotaxis. Incubation with concentrations of T3 and T4 similar to those observed in post-exercise plasma (T3, 2.3 nmol l(-1); T4, 84 nmol l(-1)) enhanced chemotaxis with respect to incubation with the basal concentrations of the hormones in control animals. A 10(4)-fold concentration of T4 reversed this effect. It is concluded that thyroid hormones stimulate macrophage chemotaxis. Also, these data support the hypothesis that thyroid hormones may be involved in exercise-induced stimulation of chemotaxis.

Animals↗

Effect of corticotropin releasing factor injected into the median eminence on growth hormone secretion in male rats.

We determined the dose-response relationship and examined the time-related effect of CRF (corticotropin releasing factor) injected directly into the Median Eminence (ME) on GH (growth hormone) secretion in conscious intact and castrated male rats. Doses of 0.25, 0.75, 1, and 1.5 nmol CRF dissolved in 1 microl of saline, or saline alone in the controls, were injected into the ME, and blood samples collected through indwelling catheters implanted in the jugular vein, 30, 60, 90, and 120 min post-injection to determine plasma GH levels by RIA. After 120 min the animals were decapitated. Trunk blood of decapitated animals was used to determine plasma testosterone and glucose levels. CRF at all the doses studied significantly decreased plasma GH in castrated and intact animals. The results suggest that in male as in female rats, CRF inhibits by itself GH secretion, at least in part, by a central action in the ME; all the doses of CRF studied suppressed GH secretion in castrated and intact males; finally, CRF at ME levels may participate in a variety of stress-related responses, including growth inhibition, through GH suppression.

Animals↗

Colorectal resection and primary anastomosis in patients aged 70 and older: prospective study.

OBJECTIVE: To assess the differences in morbidity, mortality, and other immediate postoperative results of colorectal resection with primary anastomosis in relation to age. DESIGN: Prospective study. SETTING: District hospital, Spain. SUBJECTS: 316 consecutive patients who required colorectal resection with primary anastomosis between 1991 and 1995, 155 of whom were aged <70 years and 161 who were 70 years or more. MAIN OUTCOME MEASURES: Mortality, morbidity, and hospital stay. RESULTS: 116 patients aged <70 (75%) were American Society of Anaesthesiologists (ASA) grades I-II compared with 82 (51%) aged > or =70.33 of the younger patients (21%) and 49 of the older (30%) developed complications. The anastomotic leak rate was 14% (n = 21) in the younger group and 16% (n = 26) among those aged > or =70. Median hospital stay was 14 and 15 days, respectively (ranges 8-81 and 1-120). 4 died (3%) among those aged <70 compared with 17 (11%) in the older group (p = 0.009, chi square 6.9). Mortality for elective resections was 6% (15/263) compared with 11% (6/53) for emergencies. There were no significant differences in mortality according to ASA grade between age groups. CONCLUSIONS: People aged 70 or more are not a high risk group for colorectal resection and primary anastomosis as a result of their age alone. Mortality and morbidity depend more on ASA grade and whether the operation was elective or emergency.

Age Factors↗