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Biomedical subjects

J Sancho

Publications and source records attributed to J Sancho.

At least 145 records · Page 8Linked to original sources

Dopaminergic modulation of aldosterone secretion in the normal menstrual cycle.

A group of eight normotensive female volunteers with regular menstrual cycles were studied during two menstrual cycles: a control cycle and one in which they received lisuride, a D1-D2 dopamine agonist (0.025 mg/8 hr). The following tests were performed in both halves of both cycles: 1) the response of prolactin (PRL) to thyrotropin-releasing hormone (TRH) administration; 2) the response of plasma renin activity (PRA) and plasma aldosterone (PA) to furosemide for 2 hours in the upright posture; and 3) the response of PRL, PRA, PA, plasma potassium (K), and cortisol (F) to metoclopramide administration. An increased response of PRL to TRH and PA to furosemide in the upright position and to metoclopramide were found in the luteal phase of the control study (p less than 0.05). After lisuride administration, in the interphase, differences in the responses of PRL to TRH and PA to furosemide in the upright position disappeared, whereas that of PA to metoclopramide increased further. We conclude that the increase of aldosterone normally observed during the luteal phase of the menstrual cycle is at least partly conditioned by diminished dopaminergic tone and that the response of aldosterone secretion to furosemide-induced sodium depletion and its response to metoclopramide stimulation may be modulated by two different types of dopamine receptors.

Adult↗

Quantitative measurement of human immunoglobulin E using monoclonal antibodies to distinct epitopes.

Monoclonal antibodies (MAb) which recognize distinct epitopes on human immunoglobulin E have been used to develop two-site sandwich radio- and enzyme-linked immunoassays for the quantitation of human IgE. In the first step, a purified anti-IgE MAb coated to polyvinyl or polystyrene microtiter plates specifically bound the IgE contained in the samples. In the second step, another anti-IgE MAb (either iodinated or conjugated to beta-galactosidase) directed to a different antigenic determinant was used to estimate the amount of bound IgE. This simple method permitted the determination of IgE concentrations of 10 ng/ml and greater in about 3 h. Coefficients of variation on a single day did not exceed 7.5% for IgE levels, covering a wide range of the standard curve. The values obtained on serum samples showed a good correlation with those obtained using the paper radioimmunosorbent test (PRIST).

Antibodies, Anti-Idiotypic↗

Monoclonal antibodies to distinct epitopes on human IgA and their use to IgA determination.

Several monoclonal antibodies (MAbs) against human IgA have been obtained which specifically bind to human myeloma and polyclonal IgA. Three of these MAbs have been purified and studied further. They recognize both IgA subclasses and define three distinct epitopes on the IgA molecule. These MAbs were used to develop a solid-phase radioimmunoassay (RIA) in which one MAb was immobilized and the other two were labeled with 125I. The assay has a sensitivity in the nanogram range. A good correlation was found (r = 0.97, P less than 0.001) when the solid-phase RIA was compared with a commercially available immunodiffusion technique for the determination of IgA levels in serum samples.

Antibodies, Monoclonal↗

Clinical significance of polymeric and monomeric IgA complexes in patients with IgA nephropathy.

IgA nephropathy is currently considered an immune complex (IC) disease. However, though several groups have demonstrated the presence of IgA-IC in the sera of patients by various techniques, a correlation with clinical activity of the nephropathy has not always been found. Since these assays detect (simultaneously) polymeric and monomeric IgA-IC, the pathogenicity of these two classes of complexes could not be established. In this work, we have studied in 66 patients with IgA nephropathy the existence and significance of such IC, by means of a technique described in our laboratory, based on the specific binding of secretory component for polymeric IgA. Furthermore, IgG-ICs were also determined by the standard Raji cell assay in ELISA. The prevalence of these complexes was as follows: Multimeric (polymeric and monomeric) IgA-ICs were detected in 55% of 66 patients studied, polymeric IgA-ICs in 30%, monomeric IgA-ICs in 39%, and IgG-ICs in 46%. The intermittency of all these complexes was clearly noted in sequential examinations. A significant correlation (P less than .025) with hematuria was only found with polymeric IgA-IC, but not with multimeric IgA-IC, monomeric IgA-IC, or IgG-IC. Polymeric IgA-ICs were more frequently observed at the initial phases of the disease. Analytical ultracentrifugation showed that polymeric IgA-IC was of larger size than monomeric IgA-IC. The major pathogenicity of polymeric IgA-IC is in agreement with the finding of this immunoglobulin at the mesangial level in patients and animals with IgA nephropathy.

Adolescent↗

The importance of the Fc receptors for IgA in the recognition of IgA by mouse liver cells: its comparison with carbohydrate and secretory component receptors.

The numbers of murine hepatocytes and Kupffer cells with receptors for human polymeric (pIgA) or monomeric IgA (mIgA) were determined by rosette formation with immunobeads coated with human pIgA or mIgA. About 63% of hepatocytes were found to express receptors for pIgA. Receptors for mIgA were also found in a significantly lower percentage of hepatocytes (50%). Only about 10% of Kupffer cells had this type of receptor. Blocking studies performed with purified human immunoglobulins suggested that both cells expressed a receptor that recognized the Fc portion of IgA (either pIgA or mIgA). In addition, murine multimeric MOPC-315 IgA strongly inhibited in a dose-dependent fashion the pIgA and mIgA rosette formation by both cells. When cells were incubated in the presence of a rabbit antiserum to secretory component (SC), only pIgA rosette-forming hepatocytes were partially inhibited. No such inhibition was seen when an antiserum to human IgG was used. Both galactose and mannose monosaccharides failed to inhibit the IgA rosette formation by either type of cell. These results show that murine hepatocytes, besides having SC receptors for polymeric IgA, also express receptors for the Fc portion of IgA. The carbohydrate receptors did not seem play any role in the recognition of IgA. The fact that Kupffer cells exclusively present Fc alpha R suggests that monomeric and polymeric IgA, either in form of immune complexes or not, are handled in a different manner by the liver cells.

Animals↗

Dopamine control of aldosterone secretion in end-stage renal failure.

The role of the tonic inhibitory effect of dopamine on aldosterone secretion has been investigated in 10 patients with chronic renal failure (CRF) on hemodialysis, in 8 normotensive renal transplant recipients (Tx) with normal renal function and in 8 normotensive volunteers (NV). The following tests were performed: the response of plasma aldosterone (PA) to metoclopramide administration; the response of plasma prolactin (PRL) to TRH administration, and the changes induced by Lisuride (a dopaminergic agonist, on the values of PA and PRL). The basal values of PA and PRL were higher in CRF than in NV and Tx. The inverse was true for plasma renin activity (PRA) values. The response of PA and PRL to metoclopramide showed blunted increases in CRF when compared to NV, in the absence of changes of PRA, cortisol and potassium. After TRH administration, PRL increase in CRF was also inferior. Lisuride induced a decrease of both PA and PRL both in CRF and NV. In Tx, basal values of PA and PRL were similar to NV. Nevertheless, the response to metoclopramide and TRH were partially blunted when compared to that of NV. These results point to the existence of a deranged dopaminergic regulation of aldosterone secretion in end-stage renal failure patients. The alterations are partially corrected by a well-functioning kidney graft.

Adult↗

Effect of exogenous angiotensin II infusion after one year of captopril therapy in essential hypertension.

The effect of exogenous angiotensin II on plasma renin activity (PRA), plasma renin concentration (PRC) and plasma aldosterone (PA) was investigated in a group of 8 patients with essential hypertension after one year of captopril therapy. The results were compared with those obtained in a group of 18 normotensive volunteers not on captopril. Angiotensin II was infused at increasing doses until a pressor response (increase of diastolic blood pressure by 20 mm Hg) was evoked. The normotensive volunteers exhibited the expected decline of PRA during angiotensin II infusion. However, no significant change was observed in PRA nor in PRC levels in the group of hypertensive patients. The PA values increased significantly both in volunteers and patients (P less than 0.02). The dose of angiotensin II necessary to evoke a pressor response was higher in the hypertensive patients than in the normotensive volunteers (6.0 +/- 2.6 s.d. ng/kg/min vs 2.5 +/- 0.9; P less than 0.01). We conclude that patients with essential hypertension, after chronic treatment with captopril, show no inhibition of renin secretion in contrast with the controls. They also require more angiotensin II to evoke a pressor response during infusion of this peptide.

Adult↗

Influence of lisuride, a dopaminergic agonist, on the sexual function of male patients with chronic renal failure.

The effects of Lisuride, a dopaminergic agonist, on the levels of plasma prolactin (PRL), testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and on the variations of libido and coital frequency of patients with chronic renal failure (CRF) have been investigated in a group of 20 male patients (ten normoprolactinemic and ten hyperprolactinemic). Ten patients were included in a hemodialysis program and another ten received conservation therapy (all had creatinine clearance rates below 15 mL/min). The response of PRL to TRH administration and that of LH and FSH to LH-RH administration have also been studied. Low levels of plasma testosterone found initially in all the patients, increased in both normoprolactinemic (P less than 0.05) and hyperprolactinemic patients (P less than 0.01) during Lisuride administration. PRL decreased (P less than 0.01) in both groups during therapy. The increase of plasma testosterone was greater in hyperprolactinemic patients (86% v 15% in normoprolactinemic) and was accompanied by a clear improvement in the studied parameters of sexual behaviors. The response of PRL to TRH was modified in hyperprolactinemic patients while that of LH and FSH to LH-RH was not modified, although Lisuride induced an increase of the basal value of LH (P less than 0.01) in the hyperprolactinemic group. The drug was fairly well tolerated, did not induce hypotension, and the overall incidence of side effects decreased along the study. These results stress the need for further studies with this agent in patients with chronic renal failure and sexual dysfunction.

Adult↗

Immunological abnormalities in healthy relatives of patients with IgA nephropathy.

Patients with IgA nephropathy have elevated serum levels of polymeric IgA, probably due to an increase in their synthesis by peripheral blood mononuclear cells, and specific abnormalities in the immunoregulation of IgA. The existence of familial cases of IgA nephropathy, as well as the published association of this nephropathy with some antigens of the HLA system, decided us to test the hypothesis that some of these alterations might be genetically controlled. For this reason we studied some of these immunological assays in 25 first-degree relatives of 7 patients with IgA nephropathy and 22 control subjects matched for age and sex. An abnormal immunological assay was found in at least 1 relative of all families examined. Thus, 16 of 25 relatives had a significant increase in the percentage of polymeric IgA-producing cells after 7 days of culture in the presence of pokeweed mitogen. Some derangement in the concanavalin A generation of specific IgA suppressor cells was found in 11 out of 25 relatives. These results are, though in lower frequency, similar to those seen in patients and suggest that the IgA-immunological abnormalities observed are genetic markers, even if they cannot by themselves explain the pathogenesis of the IgA nephropathy. The absence of IgA immune complexes seen in relatives as well as their high prevalence in patients suggest that in predisposed subjects other factors (genetic or not) are required for the development of IgA nephropathy.

Adolescent↗

"ESVITAF". Survey on the vitamin status of the French: relationships between nutrient intake and biochemical indicators.

The relationships between dietary data and biochemical nutritional status for vitamins B1, B2, A, E, beta-carotene, folic acid and iron have been studied using data from a survey conducted on 710 adults. Significant correlations were found between riboflavin intake and biochemical values for males only (r = -0.105, p less than or equal to 0.05), between beta-carotene intake and plasma beta-carotene (r = 0.232, for males and r = 0.292 for females, p less than or equal to 0.001), and between iron intake and plasma iron for males only (r = 0.115, p less than or equal to 0.05). Concerning nutrient densities, correlations were significant between dietary riboflavin and biochemical measure (r = 0.163, p less than or equal to 0.01 for males, r = -0.135, p less than or equal to 0.05 for females), between vitamin A intake (expressed in retinol equivalent) and beta-carotene (r = 0.212, p less than or equal to 0.001 for males, r = 0.157, p less than or equal to 0.01 for females) and for males only, between dietary iron and hemoglobin (r = 0.144, p less than or equal to 0.01). The dietary data for each nutrient were examined for their sensitivity, specificity and predictive values in identifying subjects with substandard or overstandard biochemical values. For all nutrients the positive predictive value percentage was always below 25%, the negative predictive value percentage always under 75%.

Adolescent↗

The role of IgA and IgG immune complexes in IgA nephropathy.

The presence of circulating immune complexes in 54 patients with IgA nephropathy has been studied by two different techniques. 64% of the patients had IgG immune complexes and 37% had IgA immune complexes, both determined with the Raji cell assay, and 48% of patients had IgA immune complexes with the anti-IgA inhibition binding assay (anti-IgA Inh BA). In sequential sera from individual patients, immune complexes remained persistently positive or negative in more than 50% of the cases being intermittently in the rest. The immune complexes detected by the Raji cell assay were mostly of 7-13S in size, while those detected by anti-IgA Inh BA were bigger. There was a good correlation between the serum levels of polymeric IgA and the presence of IgA complexes (Raji cell assay). A certain correlation (p less than 0.05) was found between these IgA immune complexes and the clinical activity assessed by the hematuria. A similar correlation (p less than 0.05) was found with specific polymeric IgA immune complexes studied by a method recently described. No relationship was observed between the presence of any HLA antigens and the existence of circulating immune complexes. These results support the contention that IgA immune complexes, especially those composed of polymeric IgA, may have a role in the pathogenesis of IgA nephropathy. Moreover, the high serum levels of polymeric IgA observed in these patients could contribute to the slow clearance and long persistence in the circulation of IgA immune complexes with their subsequent deposition at the glomerular mesangium.

Adolescent↗

Phenytoin in IgA nephropathy: a long-term controlled trial.

The final report of a long-term nonrandomized controlled trial of phenytoin therapy in patients with IgA nephropathy is presented. The mean time period of follow-up was 17 months (range 6-48) in the treated group (41 patients) and 14 months (range 6-36) in the nontreated group (32 patients). Both groups were comparable in age, sex, onset of the nephropathy, blood pressure and renal function. The number of episodes per year of macroscopic hematuria decreased in both groups, but was significantly lower at each time period in the treated group than in the control one. The diminution of microhematuria only occurred in the treated group. 1 patient in each group developed advanced renal failure. The mean serum IgA concentration diminished significantly in the treated group, as early as 6 months, but not in the nontreated group. There was a certain association between the presence of the HLAA2 and BW 35 antigens and the lowering of serum IgA. A normalization of the high serum levels of polymeric IgA occurred in the treated patients. A marked diminution of the Raji IgA immune complexes, well correlated with hematuria, was only observed in the treated group. However, despite the diminution of the serum IgA levels, the disappearance of the potential pathogenic IgA immune complexes and the hematuria in a number of treated patients, a progression in the percentage of global or focal glomerular sclerosis and/or vasculointerstitial lesions was seen in some of them. It is concluded that phenytoin decreases the clinical activity and corrects some of the immunological alterations of a certain number of patients with IgA nephropathy but has no valuable effects on the renal lesions. The overall results of this trial do not suggest the employment of this drug in patients with IgA nephropathy and normal renal function. Our data also suggest that a nonimmunological mechanism may be of importance in the progression of chronic renal damage in this disease.

Adolescent↗