Search PubMedSearch

Biomedical subjects

L Hernando

Publications and source records attributed to L Hernando.

At least 19 recordsLinked to original sources

Presence of circulating antibodies against brush border antigens (Fx1A) in a patient with membranous nephropathy and bilateral pyeloureteral stenosis. Comparison with idiopathic membranous nephropathy.

In a patient with membranous nephropathy and bilateral pyeloureteral stenosis with hydronephrosis, we examined the possibility that an increase in the intratubular pressure could facilitate the passage of the Fx1A antigens to the circulation. Elevated serum anti-Fx1A antibodies were detected in this particular patient by ELISA on three occasions during the disease follow-up, even though he was in clinical remission. These antibodies reacted in vitro with the tubular brush border of a normal human kidney. The anti-Fx1A antibodies isolated from the patient's sera by affinity chromatography competed with the rabbit anti-Fx1A antisera binding to plates coated with human Fx1A antigen. In immunoblotting studies the isolated specific IgG antibodies from that patient reacted with a 180 kDa antigen of the human Fx1A and with less intensity with 75 kDa and 50-55 kDa polypeptides. In none of 12 patients with idiopathic membranous nephropathy could the circulating anti-Fx1A antibodies be demonstrated. On the whole, this particular case suggests that on some occasions increased intratubular pressure could cause the release of Fx1A antigens, facilitating an autologous immunocomplex nephritis. These antigens, by contrast, do not seem to play any role in most cases of membranous nephropathy in man.

Aged

Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat glomeruli.

The effects of reactive oxygen species (ROS) on cultured rat mesangial cells were studied by measuring planar cell surface area (PCSA) after incubation with xanthine plus xanthine oxidase (XXO), in the presence of superoxide dismutase (SOD; 5 micrograms/ml) or catalase (CAT; 20 micrograms/ml), or after incubation with H2O2. Myosin light chain (MLC) phosphorylation was assessed in cells prelabeled with o-[32P]phosphoric acid and incubated with H2O2, after protein separation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible intermediate role for platelet-activating factor (PAF) was analyzed by preincubation of the cells with a PAF antagonist BN 52021 (BN, 5 x 10(-5) M) and by measuring PAF-specific [3H]acetate incorporation and immunoassayable PAF. XXO significantly decreased PCSA (14%), an effect abolished by CAT but not by SOD. H2O2 induced a similar effect, in a dose-dependent and time-dependent manner. MLC phosphorylation increased by 81 +/- 15% after H2O2 incubation, and this effect was blocked by BN. BN also completely blocked the effect of H2O2 on PCSA. PAF-specific [3H]acetate incorporation increased in the presence of H2O2 (from 6,886 +/- 2,030 to 58,703 +/- 16,063 counts.min-1.mg-1) as well as the immunoassayable PAF production by cells (from 0.90 +/- 0.19 to 6.71 +/- 2.27 ng/mg). These results suggest that ROS, particularly H2O2, could modulate the surface area of mesangial cells, modifying the ultrafiltration coefficient, thus explaining the decrease in glomerular filtration rate in those pathological situations characterized by an increased ROS synthesis. PAF could be involved in the genesis of these effects.

Animals

Effect of recombinant human growth hormone in a postpediatric hemodialysis patient with delayed growth.

We present an 18-year-old patient who has been on renal replacement therapy since the age of 11. He had growth retardation and delayed puberty, with a bone age of 13.6 years. Treatment with human recombinant growth hormone (rhGH) resulted in a clearcut increase in height and lean body mass. We emphasize that rhGH treatment could be tried even at a postpediatric age, provided bone radiology suggests that further growth is possible.

Adolescent

Renal and systemic effects of aminoacids administered separately: comparison between L-arginine and non-nitric oxide donor aminoacids.

The present study examined the mechanisms of the renal effect of the NO-donor aminoacid, L-Arg and different non-NO-donor aminoacids, namely L-Asn, L-Ala, L-Gly L-Gln administered separately. In conscious, unrestricted Wistar rats, a bolus of L-Arg produced a short-lasting decrease in mean arterial pressure. No variations in mean arterial pressure were found with either L-Gly, L-Asn, L-Ala or L-Gln. This effect of L-Arg was inhibited by NwNLA, methylene blue and atropine and not affected by meclofenamate. Simultaneously, a dose-response diuretic and natriuretic effect was observed with all the aminoacids. In further experiments with L-Arg and L-Gly, this effect was associated with increased glomerular filtration rate, renal plasma flow, fractional sodium and free water excretion and urinary cyclic guanosine monophosphate. These effects of L-Arg and L-Gly were inhibited by NwNLA. On the contrary, no inhibition by NwNLA was detected on the diuretic, natriuretic and renal hemodynamic effects of L-Gln, and the diuretic and natriuretic effects of L-Asn or L-Ala. Our results show that all the assayed aminoacids were endowed of diuretic and natriuretic capabilities. Such effects were apparently related with a NO-mediated mechanism in the case of L-Arg and L-Gly, but not in the case of L-Gln, L-Asn or L-Ala, therefore suggesting that more than one mechanism is involved in the renal effect of the different aminoacids. Simultaneously, only L-Arg produced a NO-, cyclic guanosine monophosphate-dependent hypotensive effect, which was not shared by the other assayed aminoacids.

Amino Acids

Expression and synthesis of cross-reactive idiotypic antibodies by peripheral blood lymphocytes and their suppression by anti-idiotypes in patients with IgA nephropathy.

We have recently described that patients with IgA nephropathy present high serum levels of anti-BSA idiotypic antibodies that were well correlated with the existence of hematuria. Furthermore, these Id were found in circulating and renal deposited immune complexes. In the present work, we examined the expression of surface idiotypic determinants on PBL by flow cytometry and their in vitro production, using as reagent anti-idiotypic antibodies previously well characterized. The presence of cross-reactive Id-bearing cells was observed in 5 out of 6 patients studied, with frequencies ranging from 3 to 12% of lymphocytes. After 7 days of culture, the spontaneous synthesis of idiotypic antibodies by PBL was found elevated in 6 out of 13 (46%) patients. A major Id cell expression and production was noted in patients with active disease as defined by hematuria. The preincubation of PBL with 20 and 50 micrograms of anti-idiotypic antibodies/2 x 10(6) cells for 3 days induced a significant inhibition of cross-reactive Id production in a dose-dependent fashion, with a degree of suppression between 12 and 50% in five out of six patients studied. In the above assays, as negative controls, we used the anti-Id antibodies previously adsorbed on an Id-Sepharose column. On the whole, these results suggest that patients with IgA nephropathy present dysfunctions in the Id-Anti-Id network that could play an important role in the pathogenesis of this disease.

Antibodies, Anti-Idiotypic

Inhibition by L-arginine of the endothelin-mediated increase in cytosolic calcium in human neutrophils.

The effect of endothelin (ET) on the cytosolic-free calcium [(Ca2+]i) changes in polymorphonuclear leukocytes (PMN) from normal humans and Wistar rats was investigated. ET induced a dose-related [Ca2+]i peak. This [Ca2+]i transient was blunted by TMB-8 (10(-5)M) and by Ca(2+)-free EGTA medium, therefore suggesting a role of both intracellular Ca2+ release and Ca2+ influx in the generation of the [Ca2+]i peak. Preincubation of PMN with the nitric oxide (NO)-donor L-arginine (L-Arg) markedly blocked the ET-induced [Ca2+]i transient in an enantiomerically-specific manner. A similar blunting effect of L-Arg on the fMLP (10(-7)M)-induced [Ca2+]i transient was detected. The L-Arg antagonist, NG-monomethyl-L-arginine (L-NMMA), reverted the L-Arg blocking effect on both ET- and fMLP-induced [Ca2+]i transients. These data suggest that ET has a potential role in activating Ca2+ mobilization in PMN, an effect that can be inhibited by L-Arg.

Arginine

Glomerular binding and contractile response to angiotensin II in rats with chronic experimental cirrhosis of the liver.

1. The effects of angiotensin II on glomerular filtration rate and renal plasma flow were studied in surgically instrumented conscious control and cirrhotic rats. In addition, angiotensin II binding and the contractile response to angiotensin II were studied in glomeruli isolated from cirrhotic and control rats. 2. Cirrhotic rats had a higher glomerular filtration rate and a higher renal plasma flow than control animals. A non-pressor dose of angiotensin II induced small but significant decreases in glomerular filtration rate and renal plasma flow in both control and cirrhotic rats, the effect on renal plasma flow being the most pronounced. 3. Plasma renin and aldosterone concentrations were similar in control and cirrhotic rats. 4. The cross-sectional area of glomeruli from cirrhotic rats was 42% greater than that of glomeruli from control animals. Angiotensin II (10(-9) mol/l) decreased the cross-sectional area of glomeruli from control animals by 6.4 +/- 0.9% and of glomeruli from cirrhotic rats by 6.6 +/- 0.8% (P = not significant for comparison between control and cirrhotic animals). 5. There were no differences between control and cirrhotic rats in the affinity of angiotensin II for its glomerular receptors. However, the angiotensin II receptor density was higher in cirrhotic than in control rats, thereby producing an increased total angiotensin II binding in cirrhotic rats. 6. Since no functional differences between control and cirrhotic animals were present in the response to angiotensin II, even though angiotensin II binding was increased, a post-receptor blockade of the angiotensin II signal could be present in cirrhotic rats.

Angiotensin II

Mechanisms of renal effects of different agents stimulating production of cGMP.

The effect of agents stimulating the production of guanosine 3',5'-cyclic monophosphate (cGMP) by different mechanisms was compared in conscious unrestrained Wistar rats by administration of infusions of acetylcholine (ACh), sodium nitroprusside (SNP), and atrial natriuretic peptide (ANP). ACh (10 micrograms.kg-1.min-1, n = 8), SNP (200 micrograms.kg-1.min-1, n = 8), and ANP (0.5 micrograms.kg-1.min-1, n = 7) induced natriuresis (urinary Na gradient: 399, 499, and 504 microeq/h, respectively; P less than 0.001 with respect to baseline) and diuresis (urine volume gradient: 0.87, 0.82, and 0.92 ml/h, respectively; P less than 0.001). Urinary cGMP increased (P less than 0.001) with the three agents (delta pmol cGMP/min: ACh 22.3, SNP 42.5, and ANP 48.4); in addition, a parallel increase in renal cGMP content was observed with the three agents (ACh 1.6, SNP 2.8, and ANP 3.5 times with respect to controls; P less than 0.05). Mean arterial pressure did not change with the aforementioned dose of ANP but decreased by 10 and 40% with ACh and SNP, respectively. Glomerular filtration rate increased by a similar magnitude with the three compounds. The competitive inhibitor of L-arginine, N omega-nitro-L-arginine (L-NNA), significantly decreased the diuretic, natriuretic, and hypotensive effects of ACh without affecting the actions of SNP and ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

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

Sodium excretion after bilateral adrenalectomy in rats with experimental cirrhosis.

Bilateral adrenalectomy (ADX) or a sham procedure was performed in cirrhotic and control rats. After ADX, controls increased their sodium excretion with respect to the basal values but cirrhotics did not. When sodium-loaded, the ADX cirrhotic rats retained a significant amount of the load. These data do not support a primary role of aldosterone in the impaired sodium handling by cirrhotic rats.

Adrenalectomy

An escape phenomenon from water and sodium retention induced by propranolol in rats.

Rats given a daily dose of propranolol 45 mg/kg b.wt retain water and sodium for 4 days, escaping during the 5th and 6th days in which their excretions are larger than basal values. Afterwards, in the period studied, they make a new retention and clearing is less accentuated. No relationship could be found between these retentions and plasma renin activity or renal renin content.

Animals

Aldosterone regulation in anephric patients.

The response of plasma aldosterone to hemodialysis, 3 h orthostatism, K-loading and angiotensin II and ACTH infusions has been studied. Hemodialysis, orthostatism and angiotensin II infusion do not modify aldosterone levels. By the contrary ACTH and potassium originate a significant increase in plasma aldosterone. They seem to be the main aldosterone secretion regulators in the absence of renin production.

Adrenocorticotropic Hormone