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Biomedical subjects

O Devuyst

Publications and source records attributed to O Devuyst.

At least 37 records · Page 2Linked to original sources

Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease.

Aquaporin-1 (AQP1), located in proximal tubules (PT) and descending thin limbs of Henle (DTL), and aquaporin-2 (AQP2), located in collecting ducts (CD), are channels involved in water transport across renal tubule epithelia. Using antibodies against AQP1 and AQP2, we here show expression of AQP1 and AQP2 in normal human developing and adult kidneys and in autosomal dominant polycystic kidney disease (ADPKD). Unlike in rats, AQP1 and AQP2 are expressed early during human nephrogenesis (12-wk gestation). AQP1 was first seen in developing PT epithelia, predominantly in apical cell membranes, and, at 15 wk, was also detected in DTL. AQP2 was seen in apical cell membranes of the branching ureteric bud and CD system from 12 wk and throughout development. In adult normal kidneys, AQP1 was localized to apical and basolateral membrane domains of PT and DTL, whereas AQP2 was restricted to principal cells of CD. This distribution of AQP1 and AQP2 was also seen in early stage ADPKD, except that AQP1 was mostly located in the apical membrane region of expanded PT. In end-stage ADPKD, two-thirds of the cysts expressed either AQP1 or AQP2, but these two water channels were never colocalized in the same cyst. Western blot analysis showed maximal expression of AQP1 and AQP2 in normal adult kidneys, lower levels in fetal kidneys, and decreases associated with degree of cystic progression in ADPKD. These data 1) demonstrate specific, mutually exclusive localization of AQP1 and AQP2 in human fetal and adult kidneys; 2) show that both channels are expressed early during nephrogenesis; and 3) show that the mutual exclusivity of localization is maintained even into end-stage ADPKD.

Aging

Developmental regulation of CFTR expression during human nephrogenesis.

Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA and protein are expressed in proximal and distal tubules of the human kidney, but CFTR expression pattern during human nephrogenesis is unknown. We have now studied CFTR expression in fetal kidneys by immunohistochemistry and Western blot analysis, using six antibodies against human CFTR. CFTR was expressed in 12-wk human fetal kidneys, mostly in the apical membrane region of the ureteric bud epithelial cells. By 15 wk, CFTR was also diffusely expressed throughout the cytoplasm of proximal tubules and loops of Henle. No glomerular staining was seen at any state. From 15 to 24 wk of gestation this staining pattern remained constant and also included immunoreactivity of the transitional epithelium. Western blot for CFTR was performed on membrane extracts of human fetal kidneys, using T84 cells as a positive control. A 165-kDa protein corresponding to the predicted size of CFTR was seen at 13 wk and throughout development. We also observed a 75-kDa protein that was distinctly regulated during development. This protein was detected with several antibodies against the first half of CFTR (including the regulatory "R" domain) but not with a COOH-terminal-specific antibody and had the predicted size of a functional splice variant of CFTR identified in the human kidney. These results show the complex regulation of CFTR during nephrogenesis and raise the question of the respective roles of the full-length and the splice variant CFTR proteins in the human kidney.

Adolescent

Aldosterone interaction on sodium transport and chloride permeability: influence of epithelial structure.

The effects of aldosterone on sodium transport and chloride permeability were investigated by electrophysiology in two structurally distinct epithelial used as models for the distal renal tubule: the A6 cell monolayer as compared with the amphibian skin epithelium (ASE). Short-circuit current (Isc) and transepithelial conductance (Gt) were measured in A6 monolayers incubated overnight with(out) aldosterone. Cell and shunt conductances (Gcell and Gsh) were also determined, as well as the conductive nature of the chloride pathway. These parameters were correlated with sodium and chloride fluxes in A6 cells (JNa and JCl) and compared with the data recorded across ASE (Bufo marinus). The existence of a cAMP-dependent chloride secretory pathway in A6 cells was also investigated upon exposition to arginine vasopressin (AVP) or oxytocin. When A6 monolayers were incubated with aldosterone, Gt significantly increased with respect to control preparations; this increase resulted solely from an increase in Gcell, and was reflected by a 3-fold increase in Isc. There was a significant relationship between Isc and Gcell, as well as between Isc and JNa in both control and aldosterone-stimulated preparations. The A6 clone used was devoid of cAMP-dependent chloride secretory activity and was unresponsive to AVP or oxytocin. Thus, comparison between ASE and A6 preparations revealed two major differences: unlike ASE, (i) aldosterone has no effect on Gsh and (ii) no conductive reabsorptive chloride pathway is operative in A6 monolayers tested. In addition, cobalt had no effect on electrical parameters of A6 monolayers. These observations show that difference in epithelial structure is reflected in terms of electrophysiological response to aldosterone, which suggests that cell heterogeneity could be a prerequisite for observing a conductive reabsorptive chloride pathway in aldosterone-responsive, sodium-transporting epithelia.

Aldosterone

Subtypes of Madin-Darby canine kidney (MDCK) cells defined by immunocytochemistry: further evidence for properties of renal collecting duct cells.

The Madin-Darby canine kidney (MDCK) cell line has been proposed as a model for studying intercalated (IC) cells of the renal cortical collecting duct. The IC cells are characterized by peanut lectin (PNA) binding capacity, carbonic anhydrase (CA) activity and Cl(-)-HCO3- exchange mediated by a band 3-related protein. It has been suggested that these properties are also expressed in MDCK cells. So far however, the nature of the specific protein involved in Cl(-)-HCO3- exchange, the type of CA isozyme and the relationship between these two characteristics and PNA binding, have not been investigated in MDCK cells by immunocytochemical methods. Using two antibodies raised against human erythrocyte band 3 protein and two against human erythrocyte CA I and II isozymes, our study provides evidence that a protein related to band 3 is expressed in about 5% of cultured MDCK cells; these band 3-positive cells do not bind PNA and are not reactive for CAI or CAII. About 30% of the MDCK cells bind PNA, two-thirds of which are also CAII-positive. A majority (about 65%) of MDCK cells is not reactive for the three markers used; their density is increased after incubation with aldosterone. These data indicate (i) that the Cl(-)-HCO3- exchange of the MDCK cells could be related to human erythrocyte band 3, (ii) that the CA activity of the MDCK cell line bears antigenic identity with the erythrocyte CA II isozyme and (iii) that the latter is always co-localized with PNA binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ciprofloxacin-induced hypersensitivity vasculitis.

We describe a patient in whom cutaneous vasculitis appeared after 4 days of ciprofloxacin administration. On clinical examination, papular and purpuric lesions were limited to the left axillary zone of the thorax. Skin biopsy did not show the classic leukocytoclastic image but rather a mononuclear infiltrate of the vessel walls. Except a mild increase in inflammatory parameters, there were neither autoantibodies nor biological abnormalities, and the complement level was normal. These findings suggest that ciprofloxacin-induced vasculitis displays histopathological and serologic heterogeneity.

Adolescent

Physiopathology of hypernatremia following relief of urinary tract obstruction.

We report a case of postobstructive hypernatremia, and illustrate its pathogenesis and treatment. Physicians should be aware of this condition, given its high mortality rate (up to 70%), the high prevalence of potentially obstructive prostatic disease in elderly people and the peculiar sensitivity of this age group to disorders of osmotic regulation. Knowledge of the processes involved in osmoregulation has provided insights into the pathogenesis of this condition, which includes at least three factors: (i) decreased efficacy of the thirst mechanism in elderly patients, (ii) water loss in excess of effective solutes, resulting from osmotic diuresis from urea and transient renal tubular unresponsiveness to antidiuretic hormone, and (iii) inadequate fluid administration and failure to induce a positive fluid balance. These insights led to the development of specific strategies aimed at adequate correction of hypernatremia. Initial therapy should be rapid infusion of normal saline (or half-normal saline) coupled to administration of free water to restore euvolemia and correct hypernatremia, relying on repeated calculations of the free water deficit and taking into account ongoing urinary and insensible losses.

Adenocarcinoma

Anorexia nervosa: correlation between MR appearance of bone marrow and severity of disease.

PURPOSE: To identify bone marrow abnormalities on magnetic resonance (MR) images of patients with anorexia nervosa (AN) and to correlate the findings with body mass index (BMI) and blood cell count. MATERIALS AND METHODS: The signal intensity patterns in the lumbar, pelvic, and femoral marrow spaces were evaluated on MR images obtained in 14 patients with AN and 14 control subjects. RESULTS: Six patients with AN had a waterlike signal intensity pattern either throughout the three marrow spaces (five patients) or only in the marrow cavity of the proximal femur (one patient). Results of biopsy performed in one of the six patients showed that the marrow had findings typical of serous atrophy. The BMI values and blood cell counts in the six patients were lower than those of the eight other patients with AN and the 14 control subjects. CONCLUSION: Bone marrow has an unusual signal intensity and distribution at MR imaging in patients with AN who have a low BMI value and biologic signs of bone marrow dysfunction.

Adult

Localization of a Band 3-related protein in the mitochondria-rich cells of amphibian skin epithelium.

Based on immunoblotting procedure, the isolated epithelium of amphibian skin was found to contain a 180 kDa protein which cross-reacts with a polyclonal antiserum raised against human erythrocyte Band 3. Immunoperoxidase and immunofluorescence staining techniques indicated that the Band 3-related protein was localized in the mitochondria-rich cells (MRC) of this epithelium, with characteristic apical labelling pattern. Our findings show that the putative apical anion exchanger of the MRC is immunologically related to the band 3 multigenic family, which catalyzes Cl(-)-HCO3- transmembranous exchange. It thus suggests a molecular basis for the role played by these cells in the transepithelial Cl- pathway and acid-base regulation.

Animals

Acute cholestatic hepatitis with rash and hypereosinophilia associated with ranitidine treatment.

We report a case of acute cholestatic hepatitis associated with rash and hypereosinophilia, in which the absence of transfusion, intercurrent viral infection, alcohol consumption or other hepatotoxic drugs are suggestive of ranitidine-induced hepatotoxicity. The pathogenesis of the disorder is unknown, but the lack of a dose-effect relationship, the rarity and unpredictability of the reaction, as well as the clinical signs suggest that hypersensitivity is involved. Physicians should be aware of this rare and idiosyncratic side-effect of ranitidine.

Chemical and Drug Induced Liver Injury

Haematological changes and infectious complications in anorexia nervosa: a case-control study.

To determine the prevalence of haematological abnormalities in patients with anorexia nervosa (AN), and assess the relationships between these changes, the severity of AN and the propensity to infections, we retrospectively studied 67 patients who met the DSM-III-R diagnostic criteria for AN. We recorded physical findings and routine haematological data on admission, and infectious events during hospitalization. The patients were compared with 67 normal controls matched for age and sex. Mean haemoglobin (Hb) was normal but lower in AN patients than in controls (131 +/- 19 vs. 137 +/- 11 g/l, p = 0.03) and the prevalence of anaemia (Hb < 120 g/l) was higher in the AN group (27% vs. 1.5%, p < 0.0001). Patients had a lower leucocyte count (4.94 +/- 1.9 vs. 6.78 +/- 2.4 x 10(9)/l, p < 0.0001), and increased prevalence of leucopenia (< 4 x 10(9) cells/l)(36% vs. 1.5%, p < 0.0001), neutropenia (< 1500 x 10(6) cells/l)(17% vs. 0%, p = 0.0015) and thrombocytopenia (< 150 x 10(9)/l) (10% vs. 0%, p = 0.03). Only 2 patients (3%) had pancytopenia, but 9/17 patients with anaemia (53%) also had leucopenia. There was a slight but significant correlation between body-mass index (BMI) and total leucocyte, neutrophil and red blood cell counts. Severe infectious complications occurred in 9% of AN patients vs. 0% in controls (p = 0.01); they were more frequent with neutropenia (relative risk, 15.1: 95% CI, 10-20.2) or low (< 12) BMI (relative risk, 11.6: 95% CI, 6.6-16.6) on admission. Compared with controls, AN patients thus had an increased prevalence of anaemia, leucopenia and thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent