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Biomedical subjects

F Alonso

Publications and source records attributed to F Alonso.

At least 73 records · Page 4Linked to original sources

Vascular actions of synthetic PAF-acether (a synthetic platelet-activating factor) in the rat: evidence for a platelet independent mechanism.

Since rat platelets fully responsive to thrombin and collagen did not respond by releasing 3H-serotonin with up to 10 micrograms/ml of synthetic PAF-acether, the rat, contrariwise to the rabbit, was considered to be an appropriate model to study the actions of PAF-acether not mediated through the activation of platelets and the subsequent release of their inflammatory mediators. We developed an experimental approach using 57Co and 113Sn radiolabeled microspheres to assess the effect of PAF-acether on cardiac output, peripheral vascular resistance, and regional flows and resistance. The effect on vascular permeability and blood volume was studied by measuring the clearance of 125I-HSA and the variations of the hematocrit. A significant fall in blood pressure and peripheral vascular resistance was found with doses of PAF-acether ranging from 0.05 to 5 micrograms. Moreover, the higher doses of PAF-acether also induced a marked depletion of blood volume. A significant fall in spleen, coronary, and kidney output, but not in cardiac output, was also found. Our data show that PAF-acether, by itself, induces a drop in peripheral vascular resistance and, at higher doses, also in circulating volume, accounting for both by the hypotensive effect. The redistribution of cardiac output seems to be the expression of a nonuniform action of the compound on the vascular resistance of the different organs.

Animals↗

Modulatory role of cyclic AMP in the release of platelet-activating factor from human polymorphonuclear leucocytes.

Zymosan coated with complement (Zc) was observed to induce a transient elevation of the intracellular cyclic AMP in human polymorphonuclear cells: a two- to three-fold increase was observed within 1 min after stimulation and approached prestimulation levels by 2 min incubation. These changes in cyclic AMP were not associated with significant changes in cyclic GMP levels. Zymosan caused the release of PAF and beta-glucuronidase and particle uptake, which was initiated about 5 min after stimulation. These results suggest that the transient increase in cyclic AMP content might regulate an early event during mediator release. In an attempt to study further the significance of this rise in cyclic AMP, cells were preincubated with various phosphodiesterase inhibitors. Preincubation of the cells with methylisobutylxanthine (MIX, 10(-6) M to 5 X 10(-5) M), theophylline (3 X 10(-5) to 3 X 10(-3) M) or dipyridamole (10(-6) M to 10(-4) M) enhanced the increase in cyclic AMP levels, but resulted in dose-dependent inhibition of Zc-induced mediator release. Particle uptake and beta-glucuronidase release were less sensitive than PAF release to phosphodiesterase inhibitors, which argues in favour of the independence of both phenomena. Synergistic experiments with MIX and cyclic AMP indicate that the effect of this drug is through its action on cyclic AMP levels. These results suggest that while Zc-induced cyclic AMP elevation might occur in an intracellular place critical to its effect; phosphodiesterase inhibitors may elevate cyclic AMP levels throughout the cell and therefore inhibit the biological response.

Blood Coagulation Factors↗

Functional assessment of T and B lymphocytes in patients with selective IgM deficiency.

Two patients with selective IgM deficiency were studied. Both presented with dermatitis, chronic diarrhoea, recurrent respiratory infections, failure to thrive, elevated serum IgE levels and in vivo impairment of antibody production. No phagocytic or complement abnormalities were found. B lymphocytes with surface IgM were present in normal or high percentage in peripheral blood, and produced normal amounts of IgM in vitro when co-cultured with normal T cells. Patients' T cells did not show excess suppressor function in vitro but had a decreased helper activity for IgM, IgG and IgA production. It is suggested that both patients have an extensive humoral immune deficiency that might be caused by the immunoregulatory T cell defect.

B-Lymphocytes↗

Rat serum sickness: possible role of inflammatory mediators allowing deposition of immune complexes in the glomerular basement membrane.

Serum sickness was induced in rats by a modification of previously described methods avoiding i.v. administration of the antigen. All the animals developed a progressive disease characterized by an initial pattern of deposition of IC in the mesangium followed by the appearance of GBM deposits. This change in the deposition of IC was associated with the onset of massive proteinuria and a fall in the titre of precipitating antibodies. Simultaneously, specific desensitization of platelets for a rat PAF could be demonstrated and platelet aggregates were seen in the glomeruli. The presence of homocytotropic IgGa anti-ovalbumin antibodies in rat sera during the induction of the disease was demonstrated by 2 hr PCA. Accordingly, this antibody together with the antigen ovalbumin induced the release of histamine from peritoneal mast cells, suggesting that a similar mechanism might occur in vivo during the induction of the disease. Rat PAF and beta glucuronidase could be obtained from peritoneal macrophages under similar conditions to those required for the release of histamine. The data support a role for inflammatory mediators in the increase in vascular permeability needed for the deposition of IC in the GBM and provide evidence for a new role of macrophages and PMNs in glomerular pathology in contributing to an increase in permeability of GBM.

Animals↗

Non-platelet-mediated vascular actions of 1-O-alkyl-2-acetyl-sn-3-glyceryl phosphorycholine (a synthetic PAF).

Rat platelets fully responsive to thrombin and collagen did not release 3H-serotonin with up to 10 microgram/ml synthetic PAF. Therefore, an experimental approach using 57Co and 113Sn radiolabelled microspheres was developed to evaluate the effect of PAF on cardiac output (CO), peripheral vascular resistance (PVR) and redistribution of CO among organs. The effect on vascular permeability was studied by measuring the clearance of 125I-HSA and the variations of the haematocrit. A significant fall in blood pressure and PVR was found with doses of PAF from 50 to 5000 ng. Moreover, the highest doses of PAF induced also a marked reduction in blood volume. A significant fall in spleen, coronary and kidney output was found but not in CO. Our data show that PAF, by itself, induces a fall in PVR and at higher doses also in circulating volume, both accounting for the hypotensive effect. The redistribution of CO seems to be the expression of a non-uniform action upon PVR.

Animals↗

Absence of an anaphylactic vasopermeability mechanism for immune complex deposition in the Heymann nephritis of rats.

The existence of an anaphylactic mechanism favouring the deposition of circulating immune complexes in Heymann's nephritis and its possible inhibition by disodium cromoglycate (DSCG) and antihistamines was studied. No animal produced anti-renal tubular anaphylactic antibodies (IgE and IgGa classes) and no histamine and PAF (platelet-activating factor) release were obtained when buffy coat cells (BCC) were challenged with the soluble Fx1A antigenic fraction. However, PAF was obtained from phagocytozing leucocytes. Total histamine after boiling 10(7) BCC was less than 20 ng. The frequency of nephritis and quantity of immune deposits in the glomerular basement membrane were similar in treated and control groups. Our results show that, contrary to the data obtained in acute serum sickness of rabbits, an anaphylactic mechanism in Heymann's nephritis does not seem to exist. Accordingly the treatment with antihistamines and/or disodium cromoglycate did not produce any beneficial effect upon the course of the disease.

Anaphylaxis↗

Platelet-activating factor in anaphylaxis and phagocytosis. I. Release from human peripheral polymorphonuclears and monocytes during the stimulation by ionophore A23187 and phagocytosis but not from degranulating basophils.

Platelet-activating factor (PAF) is a mediator of a anaphylaxis found initially in basophils and later in mouse and rat macrophages. The purpose of this paper was to determine the cellular origin of PAF released from human leucocytes and to establish if phagocytosis is a more important stimulus for PAF release than anaphylactic reactions. Phagocytic leucocytes (monocytes and PMNs) released PAF, physicochemically analogous to the PAF obtained by anaphylactic reactions in rabbits when challenged with zymosan, zymosan coated with complement, immune complexes, immunoglobulin aggregates or calcium ionophore A23187. Basophils failed to release PAF by anti-human IgE antibody, although positive degranulation and histamine liberaton were found. Pre-incubation of phagocytosing leucocytes with cytochalasin B or colchicine produced a diminution of PAF release, whereas beta-glucuronidase liberation was increased. The addition of carboxypeptidase B did not significantly modify PAF or beta-glucuronidase release. These data indicate that PAF obtained from preparations of human leucocytes comes from monocytes and polymorphonuclears; human basophils do not liberate measurable quantities of PAF, either by anaphylactic stimulus or by neutrophil cationic proteins; liberation of PAF and lysosomal content follow different mechanisms as they have different kinetics and are modified in an opposite way by drugs acting on the cytoskeleton.

Anaphylaxis↗

Characterization of five monoclonal antibodies specific for swine class II major histocompatibility antigens and crossreactivity studies with leukocytes of domestic animals.

A set of five monoclonal antibodies (mAb) against porcine major histocompatibility complex (MHC), or swine leukocyte antigens (SLA), class II molecules has been characterized. These mAbs appear to recognize monomorphic determinants on SLA-DR (2F4, 1F12 and 2E9/13) and SLA-DQ (BL2H5 and BL4H2) molecules, as assessed by flow cytometry and immunoprecipitation. By Western blot, the 2F4, 1F12, BL2H5 and BL4H2 epitopes were located on the beta-chains of these molecules. mAbs 2F4 and 1F12 crossreact with leucocytes of dog, cattle, horse and human; mAbs 2E9/13, BL2H5 and BL4H2 bind leucocytes of cattle but not those of human, dog and horse. These mAbs effectively blocked the mixed lymphocyte reaction and the proliferative response to viral antigens (African swine fever virus) and to staphylococcal enterotoxin B. Therefore, these mAbs can be useful reagents for studying MHC class II molecules of pig and crossreactive species, and the immunological processes where they are involved.

Animals↗

Successful unrelated umbilical cord blood transplantation in a child with Omenn's syndrome.

Omenn's syndrome is a variant of combined immunodeficiency disease (CID). Like other CID forms, it causes death unless the patient receives a bone marrow transplant (BMT). Previous reports have shown that BMTs from unrelated donors in Omenn's syndrome have very poor results, with a high rate of infections during transplantation and graft rejection, when compared with transplants from related donors or patients with other CID. This study discusses the case of a 19-month-old child with Omenn's syndrome, who received an unrelated cord blood stem cell transplant (CBT). Donor and recipient had 1 HLA-Ag mismatched on HLA-B. Symptomatology improved early after CBT. The child achieved leukocytes and platelet engraftment and was discharged on day +34. His follow-up has been uneventful and at this time, 27 months after CBT, immune functions have been recovered.

Eosinophilia↗

Pheochromocytoma and clear-cell renal carcinoma in a child with von Hippel-Lindau disease: a patient report.

A 6 year-old boy with von Hippel-Lindau (VHL) disease presented with hypertension due to bilateral pheochromocytomas. At age 13 he developed a renal carcinoma and bilateral paragangliomas. His mother had retinal angiomas, bilateral pheochromocytomas and a cerebellar hemangioblastoma. This unusual presentation illustrates the complexity and difficulties associated with the management of VHL disease.

Adrenal Gland Neoplasms↗

[Brainstem lesion in multiple sclerosis, blink reflex, and brainstem auditory evoked potentials].

Blink reflex (BR) and brainstem auditory evoked potentials (BAEP) were recorded from 168 patients with several diagnostic categories of multiple sclerosis, from which 98 complained brainstem symptoms (BSS+). From the whole group, the BR showed a higher degree of abnormality (45.75%) than BAEP (27.95). This range increased in the group BSS+ (52.15% for the BR and 34.9% for the BAEP) and even more when sings or symptoms of brainstem were present at the time of exploration (BSS+P) 60.4% for the BR and 41.3% for BAEP. Among patients who never complained brainstem symptoms, the BR disclosed a subclinical lesion in the 33.3% and the BAEP in the 16.9%. The combination of BR and BAEP were more useful than an isolated test. The localization of the lesion both clinically and in the BR were mostly on the pons. Light correlation between the presence of isolated or multiple symptoms and the disorder in the BR were present. Facial myokymia and internuclear ophthalmoplegia were most often associated with disorder in the BR, in both, the commonest localization was on the pons, and in the former about the motor nucleus of the facial nerve.

Adolescent↗

[Brainstem auditory evoked potentials (BAEP) in the rabbit. Normal patterns].

Brain stem auditory evoked potentials using skin electrodes have been studied in rabbits. The obtained records are integrated by 6 consecutive waves ranging up to 10 ms. of latency time. The most important, constant and well-performed waves were the I, II and IV waves, which persist until the auditory threshold by 10 dB. The obtained results in 50 ears have been statistically treated. Subsequently, a normal pattern of the BAEP in rabbits has been performed as a base for upcoming papers.

Animals↗