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Biomedical subjects

L Hernando

Publications and source records attributed to L Hernando.

At least 73 records · Page 4Linked to original sources
PubMed1983

Abnormalities of immune regulation in patients with IgA mesangial glomerulonephritis (Berger's disease).

Regulation of the immune response was studied in 22 patients with IgA nephropathy. A significant increase in the IgA production by Pokeweed-stimulated peripheral mononuclear cells maintained in culture for seven days was observed. These patients had significantly less IgA suppressor cell activity, as assessed by the Concanavalin A-generated suppressor cell assay, than the normal controls. The fact that most of the patients studied had increased activity of helper T cells on IgA synthesis, together with an augmentation in the percentage of OKT4+ cells, suggest that the abnormalities in helper T cell function might be the primary defect in this nephropathy. The existence of similar alterations in some of the healthy relatives of the patients further supports a genetic basis for susceptibility to this disease.

Concanavalin A↗
PubMed1983

Immune complexes in IgA nephropathy: presence of antibodies against diet antigens and delayed clearance of specific polymeric IgA immune complexes.

Several features suggest that IgA nephropathy is an immune complex (IC)-mediated disease. The source of antigen(s) is unknown but the predominant involvement of IgA suggest that it is associated in some way with the gut or respiratory tract. Taking into account the specific hepatobiliary transport by polymeric IgA of circulating antigens entering through the mucosal surfaces we examined the possible involvement of antibodies against food antigens in the circulating IC and the existence of a defect in their blood clearance in patients with IgA nephropathy. A rise in multimeric IgA-IC (Raji assay) occurred in three of seven control subjects with a peak at 2-4 h after food ingestion. The amount of multimeric IgA-IC present at fasting in four out of six patients, diminished 2-4 h after food challenge, reaching a new peak around 6 h. At fasting, three out of six patients had IC containing antibodies against diet antigens (e.g. ovalbumin). These IC paralleled, both in patients and controls, the levels of multimeric IgA-IC. In patients small multimeric IgA-IC predominated at fasting and 24 h after food ingestion, while larger IC were detected at 2-4 h of food challenge. The specific polymeric IgA-IC showed in controls a maximal peak with similar distribution to that of multimeric IgA-IC, but with a quicker disappearance from the circulation. By contrast, polymeric IgA-IC remained elevated 24 h after food ingestion in most patients. These results suggest that antibodies against common antigens are within circulating IC and that a defect in the hepatic clearance of circulating polymeric IgA-IC exists in patients with IgA nephropathy.

Antibodies↗
PubMed1983

Delayed clearance of specific polymeric IgA immune complexes in patients with IgA nephropathy.

The presence of multimeric (polymeric and monomeric) IgA immune complexes (IC), detected by Raji cell assay and by the inhibition binding assay, as well as the specific polymeric IgA-IC were examined before and after the ingestion of 100 g protein. A rise in multimeric IgA-IC occurred in three out of seven controls with a peak at two to four hours after the meal, being cleared thereafter. The amount of multimeric IC present at fasting in four of six patients diminished at two to four hours after food challenge reaching a new peak around six hours. In both controls and patients, IC containing antibodies against diet antigens (e.g. ovalbumin) paralleled those of multimeric IgA-IC. In controls the specific polymeric IgA-IC presented a maximal peak with distribution similar to multimeric IgA-IC, but with a faster disappearance from the circulation. By contrast, polymeric IgA-IC remained elevated 24 hours after food ingestion in most patients. These results suggest that a defect in the hepatic clearance of circulating polymeric IgA-IC exists in patients with IgA nephropathy.

Adult↗
PubMed1982

Functional compensatory changes after unilateral nephrectomy in rats. General and intrarenal hemodynamic alterations.

Cardiac output (CO), total peripheral resistance (TPR), renal blood flow (RBF), renal vascular resistance (RVR) and intrarenal blood flow distribution have been measured 48 h after unilateral (right) nephrectomy (UNX) and in sham-operated rats (SO). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined using standard inulin and PAH clearances. Superficial single nephron GFR (SNGFR) was measured by free-flow micropuncture techniques. Extracellular fluid volume (ECV) and plasma volume (PV) were also determined. UNX rats showed increases of 17.4% in remnant kidney GFR and 34.5% in RPF. Filtration fraction was decreased to 0.27 +/- 0.01 (control value 0.31 +/- 0.01; p less than 0.0025). SNGFR was 45% higher in UNX rats and the ratio SNGFR/GFR increased by 28%. Cardiac output also increased (33.6 +/- 1.0 for UNX rats; 28.0 +/- 1.2 ml/min/100 g BW for SO rats; p less than 0.0025) accompanied by a corresponding fall (20%) in TPR. Left kidney RBF increased by 22%, whereas RVR decreased by 21%. Blood flow through individual glomeruli increased in the outer and inner cortex and was unchanged in the midcortex. In conclusion, 48 h after unilateral nephrectomy, rats showed a hyperdynamic circulatory state with increased CO and decreased TPR; this could be involved in the acute adaptive functional and renal changes reported after uninephrectomy.

Animals↗
PubMed1982

Role of hemodynamic alterations in the partial protection afforded by uninephrectomy against glycerol-induced acute renal failure in rats.

Systemic and renal hemodynamics and body fluid volumes were evaluated in 48-hour uninephrectomized (UNX) and sham-operated (SO) rats, 3 h after glycerol-induced acute renal failure (ARF). UNX rats showed a 20% increase in cardiac output (CO) and renal blood flow (RBF) and a 20% decrease in total peripheric resistance (TPR) and renal vascular resistance (RVR) with respect to the control rats. There was no difference in body fluid volumes. 3 h after ARF induction UNX rats showed a minor decrease in RBF and GFR and a minor increase in RVR when compared with the control rats. CO decreased to similar levels in both UNX and SO rats. Mean arterial pressure and TPR increases were observed in UNX and SO rats but these increases were higher in the UNX than in the SO rats. Plasma and extracellular volumes were reduced in both groups of rats. The partial protection afforded by the renal mass reduction against the glycerol-induced ARF seem to be explained by the minor decrease in RBF and the lesser increase in RVR exhibited by the UNX rats after ARF induction.

Acute Kidney Injury↗
PubMed1982

DNA release and appearance of antinuclear antibodies in chronic hemodialysis patients.

The presence of free serum DNA and/or antibodies against nuclear antigens was studied in 65 patients in chronic hemodialysis. Most of patients showed increased levels of both free single-stranded DNA (ss DNA) (28 out of 29) and native (double-stranded) DNA (n DNA) (25 our of 28) at the beginning of each dialysis session (69 +/- 26 vs. 119 +/- 14, p less than 0.05) suggesting a rapid in vivo degradation of the n DNA released. 15 out of 65 patients (23%) developed low anti-ss DNA antibody titers by Millipore filtration assay. 2 of them presented anti-n DNA antibodies simultaneously. Isolated anti-n DNA, anti-Sm and anti-RNP antibodies were systematically negative in all patients. No relationship was found between the presence of anti-ss DNA antibodies and the type of nephropathy, the duration of treatment and the method of dialysis. The fate of a renal allograft was studied in 12 patients after having measured serum-free DNA and anti-DNA antibodies. The 4 patients with good graft function after 2 years of transplantation had significantly higher circulating ss-DNA levels than the other 8 patients whose grafts were rejected.

Antibodies, Antinuclear↗
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↗
PubMed1981

Hyperprolactinemia in chronic renal failure: impaired responsiveness to stimulation and suppression. Normalization after transplantation.

(PRL) secretion was investigated in 12 undialyzed patients with chronic renal failure (CRF), 30 hemodialyzed patients (HD), 19 renal transplant (RT) recipients and 17 controls. Basal PRL levels in CRF and HD patients were higher than in controls and RT subjects. Plasma PRL values were higher in CRF than in HD patients. In the HD group, plasma PRL concentrations were significantly higher in men with reduced sexual potency than in those in which it was normal. After TRH stimulation in CRF and HD the PRL response was considerably less and the time of peak delayed with respect to the controls. In RT subjects PRL did not return towards baseline after 120 min. After bromocriptine, plasma PRL suppression in CFR and HD patients ws lower than in controls and RT subjects. These findings suggest that some factor which accumulates in uremia, is only partially removed by hemodialysis, and might be responsible for the hyperprolactinemia and might also interfere with the binding of TRH and bromocriptine to their respective pituitary receptors. Although a pituitary defect seems to be prevalent, a concomitant hypothalamic disorder cannot be excluded. Hyperprolactinemia seems to play a role in the sexual disturbances showed by some HD men. Whatever the alterations responsible for the impaired PRL regulation in uremia are, they are reversed by successful renal transplant.

Adolescent↗
PubMed1981

Pathogenesis of hyperprolactinemia in uremic rats.

Experiments have been carried out in order to clarify to what extent the absence of PRL renal catabolism in experimental renal insufficiency is responsible for the high PRL circulating levels. Furthermore, the relative contribution of the glomerular filtration rate and peritubular degradation to PRL renal clearance have been assessed. Circulating PRL basal levels were measured by RIA in sham-operated and intact control rats and in three uremic rat models: urine autoinfusion, bilateral ureteral ligation, and bilateral nephrectomy. Plasma PRL basal levels (nanograms per ml; mean +/- SEM) were increased in sham-operated rats (30.3 +/- 5.1) with respect to control animals (18.5 +/- 2.7; P less than 0.05). Bilaterally nephrectomized animals (66.4 +/- 16.4) and those with bilateral ureteral ligation (69.3 +/- 15.9) developed similar hyperprolactinemia, in contrast to urine-autoinfused rats (20.2 +/- 2.1; P less than 0.005) whose hormone levels were similar to those of control animals. Creatinine levels were markedly elevated and comparable in the three uremic rat groups. The results suggest that: 1) hyperprolactinemia in rats in acute renal insufficiency is due primarily to reduced renal function; 2) PRL renal catabolism in the rat requires a certain rate of glomerular filtration; and 3) PRL peritubular degradation does not seem to be relevant in PRL catabolism by rat kidney.

Acute Kidney Injury↗
PubMed1981

Study on the natriuretic activity in the suprahepatic plasma after portal hypertonic NaCl infusion in dogs.

The involvement of the liver in the control of the renal excretion of water and sodium can be deduced from some recent investigations. Hypertonic or isotonic sodium chloride infusion into the hepatic portal vein enhanced renal sodium excretion when compared with identical infusions into a systemic vein. It has been suggested that a humoral factor produced by the liver could be a functional link between the liver and the kidney. In order to test this hypothesis, the present experiments were carried out in two groups of anesthetized dogs. Animals from group I were infused with NaCl (855 mmol/l) at a rate of 0.05 ml/min/kg b.w. during 30 min, into the portal vein. Blood samples were withdrawn from the suprahepatic vein, before (SH1) and coinciding with the maximal natriuresis after hypertonic saline infusion (SH2). Plasma from SH1 and SH2 were infused into the left renal artery (LRA) of dogs from group II. Two 20 min clearance periods were performed before and after each SH-infusion. After both SH-infusions urinary sodium excretion (UNaV) was significantly increased from preinfusion values in both kidneys, and these increases were significantly greater after SH2 than after SH1. No significant differences were found in UNaV between left and right kidney. After both plasma infusions the increases in urinary volume and osmolar clearance were higher in the infused than in the not infused kidney. These results suggest that the plasma leaving the liver contains a substance with natriuretic activity and that the infusion of hypertonic NaCl into the portal vein could induce either a higher secretion of the same substance or the presence of other different substance.

Animals↗
PubMed1980

Evidence of sensitized basophils in renal transplanted patients.

The participation of basophil polymorphonuclear leukocytes in the response to kidney allografts in man has hardly been studied. In 23 patients, followed from the immediate post-transplant period for several years, the number of circulating basophils, expressed either as absolute number or as percentage of leukocytes, was significantly low in relation to that of controls. IgE on the basophil surface was determined by radioimmunoassay in 14 patients. All patients but one had elevated numbers of IgE molecules per basophil, values being higher in patients with cadaver grafts and in patients with a graft functioning at 6 months or less. When the count of circulating basophils was roughly normal, six of the eight patients showed a positive basophil degranulation test against the donor lymphocytes. These results suggest the existence of specific IgE antibodies for HLA antigens in renal transplanted patients.

Basophils↗
PubMed1980

Evidence of an immediate hypersensitivity mechanism in systemic lupus erythematosus.

In 30 patients with systemic lupus erythematosus the number of a circulating basophils was countered in different stages of activity. An inverse correlation was found between the absolute basophils count and anti-DNA antibodies and presumptive circulating immune complexes (as judged by polyethylene glycol precipitation of serum). A positive correlation was found between the absolute basophil count and C3 or C4 levels. IgE on the basophil surface was determined by radioimmunoassay in 7 patients. All of them showed a significantly higher surface IgE number. When the count of circulating basophils was roughly normal, 5 out of the 6 patients showed a positive basophil degranulation test with native DNA. These results suggest the existence of an anti-DNA specific IgE in lupus patients. Depression of the circulating basophil count may be a useful index of lupus activity.

Antibodies, Antinuclear↗