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Biomedical subjects

J Sancho

Publications and source records attributed to J Sancho.

At least 181 records · Page 10Linked to original sources
PubMed1982

Detection of monomeric and polymeric IgA containing immune complexes in serum and kidney from patients with alcoholic liver disease.

The purpose of this study was to characterize circulating IgA and the IgA deposited in the glomeruli of patients with alcoholic liver disease. In the 6 patients studied there was an increased proportion in monomeric IgA (3.5 fold) and IgA between 9-13S (8.94 fold), 13-17S (4.49 fold) and 17-21S (1.63 fold) fractions on 5-40% sucrose density gradient ultracentrifugation at physiological pH. All fraction between 9.12S decreased at acid pH, however a 3.28 fold increase in fractions where polymeric IgA is expected to appear. IgG eluted at acid pH from autopsy kidney was studied by the same procedures. At pH 7.4 about 55% of that IgA have a molecular weight comprised between 9-12S, decreasing to around 25% at acid pH. The existence of true polymeric IgA in serum and kidney was based on the capacity of high molecular weight IgA to bind human secretory component. The amount of immune complexes with monomeric IgA were higher than those with polymeric IgA in serum as well as in kidney. However, the percentage of heavy IgA (probably polymeric IgA) in kidney were, in each patient, higher than those observed in serum. Our results show the presence of high amounts of monomeric and polymeric IgA, both partially as immune complexes, in serum and kidneys of patients with alcoholic liver disease and IgA glomerulonephritis. Furthermore, our data suggest a role for human liver in the clearance of serum IgA such as has been demonstrated in the some animal species, especially in rats.

Antigen-Antibody Complex↗
PubMed1982

Increased rates of polymeric IgA synthesis by circulating lymphoid cells in IgA mesangial glomerulonephritis.

Recently we have described the existence of high levels of polymeric IgA, partially as immune complexes, in the serum and kidney from patients with IgA mesangial glomerulonephritis. As these patients often have macroscopic haematuria, following upper respiratory tract infections, our working hypothesis in this paper was that circulating lymphocytes from secretory tissues after viral stimulus could produce in these patients a large amount of polymeric IgA. To test it, peripheral blood lymphocytes (PBL) from patients and controls were cultured for seven days in the presence or absence of pokeweed mitogen (PWM). In cell culture supernatants immunoglobulin synthesis was measured by RIA and the proportion of polymeric and monomeric IgA was determined on Ultrogel Ac A22 column. There was no difference in spontaneous production of immunoglobulins between patients and controls. On the contrary, the IgA synthetized by PWM-stimulated PBL was significantly higher in patients than in controls. The percentages of IgA with molecular weight between 600,000 and 250,000 after supernate fractionation were significantly higher in patients than in controls. The true nature of polymeric IgA was confirmed by their ability to bind secretory component, the existence of covalent structures, and the decrease of the larger forms of IgA after reduction and alkylation. The percentage of IgA producing cells binding secretory component was significantly higher in patients than in controls (69 +/- 21 versus 44 +/- 27) after seven days of culture. IgM and IgG produced in patient culture were similar to controls. These results show that mitogen stimulated PBL from patients with Berger's disease synthetized a large amount of true polymeric IgA. It is suggested that a similar situation could occur in vivo after viral of other stimuli.

Cells, Cultured↗
PubMed1982

Handling of soluble IgA aggregates by the mononuclear phagocytic system in mice. A comparison with IgG aggregates.

We have studied the fate of soluble stable aggregates of human IgA (A-IgA) and IgG (A-IgG) after their injections in mice, as well as in vitro catabolism by liver, kidney and peritoneal macrophages. The half-life of the fast component of blood clearance was similar for both aggregates. However the half-life of the slow component of A-IgA clearance was significantly slower than A-IgG (t1/2 10 . 03 v. 7 . 52 hr, respectively). The A-IgA deposited in liver and kidney was removed significantly more slowly than A-IgG. Studies in isolated liver and kidney slices suggest that this could be due to the impaired catabolism of A-IgA as opposed to that of A-IgG. Interestingly the kidney hardly participates in the processing of A-IgA. At the three doses employed (1, 5 and 10 micrograms of both aggregates) peritoneal macrophages bound and catabolised significantly less amount of A-IgA than A-IgG. Complement seems to have no role in the processing of A-IgA by peritoneal macrophages unlike that observed with A-IgG. It is suggested that the impairment in handling of A-IgA by the mononuclear phagocytic system could provoke their persistence in the circulation and deposition at sites susceptible to injury. These results may be of some relevance for the understanding of physiological IgA-IC (immune complex) clearance and for the pathogenesis of IgA-related diseases.

Animals↗
PubMed1981

[The PABA test in chronic pancreatitis: value of plasma para-amino benzoic acid determinations (author's transl)].

Plasma concentrations and urinary excretion of para-aminobenzoic acid (PABA) were measured over a 6-hour period after administration of N-benzoil L-tyrosyl aminobenzoic acid (NBT-PABA) to 15 patients with chronic pancreatitis and 15 controls. The sum of plasma PABA concentrations at 1 hour and 2 hours was calculated for each subject. The resulting value proved to have a specificity of 100% and a sensitivity of 80%, as opposed to 86% and 67% respectively for urinary concentrations.

4-Aminobenzoic Acid↗
PubMed1980

Effect of insulin in vivo on the synthesis of free fatty acids (FFA) in chicken heart and skeletal muscle.

The effect of insulin on the synthesis of free fatty acids from glucose in the skeletal and heart muscles of chicken is examined. 10 min after glucose-(U-14C) administration, labeled free fatty acids (FFA) appeared in both skeletal and heart muscles. 0.75 IU of insulin kg-1 b. wt significantly increased the labeled FFA at the 30, 60 and 120 min intervals, with a maximum at 60 min.

Animals↗
PubMed1980

IgA glomerulonephritis (Berger's disease): evidence of high serum levels of polymeric IgA.

Eleven out of 15 patients with IgA mesangial glomerulonephritis (Berger's disease) had an increased proportion of serum IgA in 9-21S fractions on 5-40% sucrose density-gradient ultracentrifugation; the heavier fractions decreased at acid pH. Serum IgA purified by starch electrophoresis was subjected to reduction-alkylation yielding fragments of lower molecular weight. J chain was detected on urea alkaline polyacrylamide electrophoresis and the high-molecular weight IgA bound the human secretory component. In six patients treated with phenytoin for 1 year there was a decrease in polymeric IgA and an increase in monomeric IgA adopting a pattern similar to that of the controls. Our results show the presence of a large amount of true IgA polymers, partially as immune complexes, in the serum of patients with Berger's disease. These data together with their normalization after phenytoin treatment may open a new pathogenic and therapeutic approach to this entity.

Antigen-Antibody Complex↗
PubMed1980

A possible common pathogenesis of the mesangial IgA glomerulonephritis in patients with Berger's disease and Schönlein-Henoch syndrome.

High serum levels of polymeric IgA, partially as immune complexes, have been found in patients with Berger's disease and Schönlein-Henoch syndrome. Polymeric IgA was also found in the renal mesangium in both entities as judged by its affinity for the human secretory component. These data reinforce the clinical and morphological suspicion that both entities may represent variations of the spectrum of the same disease.

Fluorescent Antibody Technique↗
PubMed1979

Insulin effects on glucose utilization by human lymphocytes.

In recently isolated human lymphocytes, no effect of insulin on (U-14C) glucose incorporation into CO2, triglycerides and glycogen, was found over a wide range of insulin concentration. The rates of glucose oxidation, synthesis of triglycerides and synthesis of glycogen are much lower than those observed in chicken and rat adipocytes. The authors discard the possibility of using the human lymphocyte as an instrument in the study of the insulin action on normal and altered human physiology.

Glucose↗
PubMed1979

Evidence of high polymeric IgA levels in serum of patients with Berger's disease and its modification with phenytoin treatment.

High levels of polymeric IgA were found in the serum of patients with IgA glomerulonephritis. In four of the patients the IgA percentage distribution was established by ultracentrifugation in sucrose density gradients before and after six months of phenytoin treatment. A decrease in polymeric IgA, adopting a pattern similar to the controls, was observed. These findings may have both pathogenic and therapeutic implications.

Centrifugation, Density Gradient↗
PubMed1978

Volume as a determinant of plasma aldosterone in anephric man.

Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI), produces a prompt and profound suppression of plasma renin activity (PRA) and plasma aldosterone concentration (PA) without concomitant alterations in serum sodium and potassium concentrations. The NI model was utilized to assess the responsiveness of PA to volume expansion in 12 anephric subjects. The patients were studied on 2 occasions, 48 h after their last dialysis: during a seated control study (7 of the patients) and during 3 h of NI (all 12 patients). The conditions of seated posture and time of day were identical. Blood for PRA, PA, and cortisol was obtained at 30-min intervals for 5 h. PRA was undetectable in all patients. NI failed to alter PA. Plasma cortisol declined progressively throughout NI; serum potassium concentration remained unchanged. An identical NI study in normal subjects suppressed PA by 60%. These data demonstrate that when plasma composition and posture are maintained constant, marked central hypervolemia does not alter PA in anephric man. The present findings support the role of the renin-angiotensin system as the prepotent mediator of volume-induced changes in PA.

Adult↗
PubMed1978

A direct microassay for aldosterone in plasma extracts.

We previously described an RIA for aldosterone based on highly specific antibodies elicited with aldosterone-3,20 dioxime bovine gamma-globulin (Poulsen, K. J. Sancho, and E. Haber, Clin Immunol Immunopathol 2: 373, 1974). We now report the development of higher affinity antibodies of similar specificity that allow the direct measurement of normal aldosterone concentrations in extracts of 100 microliters plasma. The detection limit at +/- 2 SD of mean zero value was 0.2-0.3 pg. The assay was validated by 1) zero values in adrenalectomized plasma, 2) parallel displacement plots of aldosterone standards and plasma extracts, 3) 97.7 +/- 2.5% recovery of added tracer, 4) a correlation coefficient of 0.992 and a slope of 1.08 in a plot of added vs. recovered unlabeled aldosterone, 5) 10.2% interassay variation and 5.6% intraassay variation, and 6)failure of high concentrations of a variety of steroids added to plasma to perturb the measured aldosterone concentration. The simplicity of the assay results in a high degree of productivity, in that 195 plasma samples may be processed in duplicate, in addition to standard curves, in a single working day.

Aldosterone↗
PubMed1976

The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects.

To examine the role of angiotensin II in the maintenance of blood pressure and the control of aldosterone secretion in man, eight normal subjects were studied on a tilt table in sodium replete and sodium depleted states prior to and subsequent to the intravenous infusion of an angiotensin converting enzyme inhibitor (CEI). In both the sodium replete or sodium depleted state, upright tilting resulted in an increase in heart rate and a narrowing of pulse pressure. None of the sodium replete or depleted subjects fainted. Tilting was accompanied by a rise in plasma renin activity with an associated rise in plasma aldosterone concentration. When converting enzyme inhibitor was administered, which blocked the generation of angiotensin II, sodium replete subjects were able to compensate for an upright tilt, despite the absence of angiotensin II, without significant hemodynamic change when compared to control state. In sodium depleted subjects, after the administration of converting enzyme inhibitor, there was a sharp and significant decrease in systolic and diastolic blood pressure associated with a significant rise in heart rate. All but one sodium depleted subject fainted within seven minutes. Both plasma aldosterone concentration and plasma renin activity rose on tilting in both sodium replete and sodium depleted subjects. After the administration of converting enzyme inhibitor, plasma aldosterone failed to rise in association with a rise in plasma renin activity. In supine subjects, after the administration of converting enzyme inhibitor, plasma renin activity rose but plasma aldosterone concentration fell. In sodium depleted subjects, after the administration of CEI, aldosterone fell to a level significantly lower than that in supine controls and to a level no different from the supine sodium replete subject. These results indicate that angiotensin II is essential for blood pressure maintenance in sodium depleted individuals, that angiotensin II exerts a direct feedback control on renin secretion, and that angiotensin II is the primary stimulus to aldosterone secretion in response to both sodium depletion and to posture.

Adult↗