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Biomedical subjects

M Sich

Publications and source records attributed to M Sich.

12 recordsLinked to original sources
PubMed2001

Glomerular extracellular matrix and growth factors in diffuse mesangial sclerosis.

UNLABELLED: Diffuse mesangial sclerosis, isolated (IDMS) or observed in the context of Denys-Drash syndrome (DDS) due to WT1 mutation, is characterized by early onset nephrotic syndrome progressing to renal failure. A striking morphological feature is the rapid development of glomerulosclerosis. THE AIMS OF OUR STUDY WERE: (1) to analyze the glomerular distribution of extracellular matrix (ECM) antigens at the early stage of DMS, (2) to determine the composition of the ECM accumulated within the mesangial areas and leading to glomerular sclerosis, and (3) to analyze the expression of growth factors, transforming growth factor-beta 1 (TGF beta 1) and platelet-derived growth factor A (PDGFA). In glomeruli of patients with IDMS and DDS, the glomerular basement membrane (GBM) expression of the heparan sulfate chain of heparan sulfate proteoglycan (HSPG) was decreased from the early stage of DMS, at a time when ECM proteins retained a normal distribution. In fully developed lesions, mesangial and subendothelial accumulation of collagenous and noncollagenous glycoproteins normally expressed in the mesangial area (types IV [alpha 1(IV)2 alpha 2(IV)] and VI collagen, beta 1 laminin, fibronectin, tenascin, and perlecan) increased with progression of mesangial sclerosis. This was associated with mesangial expression of proteins normally restricted to the GBM (agrin, alpha 1/alpha 5, beta 2, and gamma 1 laminin chains) and with accumulation of chondroitin sulfate proteoglycan. The distribution of the alpha 3-alpha 5 chains of type IV collagen was normal. Focal accumulation of types I, III, and V collagen was seen only in severely sclerotic glomeruli. Expression of growth factors TGF beta 1 and PDGFA was increased in 9 of 10 and 5 of 10 patients, respectively. Early decreased GBM expression of the heparan sulfate chain of HSPG could play a role in the proteinuria of DMS patients. Changes in the composition of the ECM accumulated within the mesangial areas are not specific. We speculate that deregulation of the expression of growth factors normally downregulated by WT1, is one of the factors responsible for the rapid and massive mesangial deposition of basement membrane material in DDS.

Child↗
PubMed2000

Distribution of iron oxide nanoparticles in rat lymph nodes studied using electron energy loss spectroscopy (EELS) and electron spectroscopic imaging (ESI).

Superparamagnetic iron nanoparticles have been developed as contrast agents for magnetic resonance lymphography. The kinetics of uptake of these particles has not yet been accurately determined. We have therefore monitored the distribution of individual iron particles (ferumoxtran, AMI-227, Sinerem) in rat lymph nodes 1.5, 3, 6, 12, and 24 hours after i.v. injection (two rats per time point). The ultrastructural distribution of the iron was determined by energy-filtered transmission electron microscopy (EFTEM). This method allows the identification of elements using element-specific energy-loss electrons. Iron was identified by the Fe-L(2,3) edge (EELS), and iron maps were obtained using iron-specific electrons for imaging (ESI). The background was calculated by simplex optimization (EELS) and by the two-window method (ESI). Ferumoxtran particles were regularly observed at the periphery of the lymph nodes but not in their centers. Isolated iron particles were seen extracellularly within lymph vessels and, 3 hours after injection, as small dots in phagocytic cells. Numerous dense clusters appeared within the cells at later times (6 and 12 hours after injection). These results suggest that the contrast agent moves rapidly across the capillary wall to the lymph and is then taken up by phagocytic cells. J. Magn. Reson. Imaging 2000;12:505-509.

Animals↗
PubMed2000

MR lymphography using iron oxide nanoparticles in rats: pharmacokinetics in the lymphatic system after intravenous injection.

The objective of the study was to quantify the kinetics of the superparamagnetic nanoparticle ferumoxtran (AMI 227, Sinerem(R), Combidex(R)) in the efferent lymph of the subdiaphragmatic lymph nodes and in various node groups of the rat to elucidate the uptake mechanism. The thoracic lymph duct was catheterized in 24 rats after an IV injection of 40 micromol Fe/kg ferumoxtran. Three rats were studied at several time points between 1.5 and 24 hours. At each time point, 0.3 ml of lymph were collected over 45 minutes. Lymph nodes were differentiated into five groups. The iron concentration in the samples and in plasma was measured by relaxometry at 0.47 T and atomic absorption spectrometry. Cytology was performed on the lymph. High concentrations of nanoparticles were found in the thoracic lymph soon after injection (90 minutes). No particle was found in the lymph cells, indicating that ferumoxtran was extracellular in the lymph fluid. The maximum concentration was reached later in all node groups, at 12 hours, and then plateaued. The transcapillary pathway and subsequent lymph drainage of the particles seem to play a major role in the delivery to the lymph nodes.

Animals↗
PubMed1996

Collagen distribution in focal and segmental glomerulosclerosis: an immunofluorescence and ultrastructural immunogold study.

Focal and segmental glomerulosclerosis (FSGS) is a non-specific scarring process of the glomerulus, initially described in idiopathic nephrotic syndrome. The distribution of types I, III, IV, V, and VI collagen and of the alpha 1, alpha 3, alpha 4, alpha 5, and alpha 6 chains of type IV collagen was studied by immunohistochemistry in sclerotic lesions of nine nephrotic children. Dual immunofluorescence and high-resolution immunogold labelling were used to determine the precise distribution of the antigens. No changes were detected in normal glomeruli of patients compared with controls. In FSGS, type IV collagen [alpha 1(IV)2 alpha 2(IV)], and to a lesser degree type VI, accumulates in the two components of the lesion: the enlarged mesangial matrix and the material deposited between the pushed-out podocytes and the alpha 3-alpha 5(IV)-positive glomerular basement membrane. Staining for alpha 6(IV) and types I, III, and V collagen was practically negative. These results suggest that the matrix components of the sclerotic lesion are produced solely by glomerular cells. Changes in the relative distribution of type IV collagen chains, characterized by the presence of collagen [alpha 1(IV)2 alpha 2(IV)] in close contact with the podocytes, strongly suggest a switch in the podocyte programme of collagen synthesis.

Adolescent↗
PubMed1996

Collagen distribution in human membranous glomerulonephritis.

In membranous glomerulonephritis (MGN), thickening of the glomerular basement membrane (GBM) is partly due to the accumulation of basement membrane material between and around immune deposits located on the epithelial aspect of the GBM. We investigated the distribution of type IV collagen chains (alpha 1/alpha 2, alpha 3, alpha 4, alpha 5, alpha 6) and of types I, III, V, and VI collagen in the glomeruli from 16 patients, by indirect immunofluorescence in 13 and the high-resolution immunogold technique in 6. No changes were detected in stage I MGN. The spiky projections of the GBM in stage II MGN and the basement membrane layers encircling immune deposits in stage III contained the alpha 3, alpha 4, and alpha 5 chains of type IV collagen. In contrast, the alpha 1/alpha 2 chains of type IV, as well as type VI collagen accumulated in the subendothelial aspect of the GBM. No significant staining for types I, III, and V collagens or for the alpha 6 chain of type IV collagen was detected. The results show that, as in the normal glomeruli, the different chains of type IV collagen are not co-distributed in the glomerular extracellular matrix in MGN. They also indicate that type IV collagen chains and type IV collagen play an important role in the thickening of the GBM in human MGN.

Adolescent↗
PubMed1992

Effects of epidermal growth factor on calf renal glomerular cells in vitro.

Epidermal growth factor (EGF) stimulates the mitosis and differentiation of a variety of cellular types. It also delays the cell senescence in vitro. Because of its multiple functions, the effects of EGF on cells from isolated, explanted calf renal glomeruli have been studied. The cell types emerging from glomeruli cultured with and without EGF were compared and identified by morphological, immunofluorescence and electron microscopy criteria. Two cell types: visceral epithelial cells or podocytes (type I) and mesangial cells (type II) emerged from glomeruli cultivated without EGF. A third cell type, called type III cells, appeared only in the presence of EGF. These cells divided, were mobile and had prolonged lifespan in culture. They appeared pavement-like, and acquired progressively the morphological features and cytoskeletal components of type I cells. They also showed certain characteristics of podocytes in vivo. We suggest that type III epithelial-like cells are precursor cells of podocytes, that EGF triggers their emergence from glomeruli and their subsequent proliferation and differentiation in vitro. EGF also prolongs their lifetime in culture.

Animals↗
PubMed1987

Ontogenesis of 28 kDa vitamin D-induced calcium-binding protein in human kidney.

The kidney distribution of 28 kDa vitamin D-induced calcium binding protein (CaBP) was studied in 15 fetuses (11 to 33 weeks old), six children and adults (12 days to 32 years old) by immunocytochemistry using a specific antibody to rat renal 28 kDa CaBP. Similar results were obtained on frozen and fixed tissues. Kidneys from one adult and three fetuses were studied by immunoelectronmicroscopy for antigen localization at the subcellular level using the indirect immunoperoxidase technique. The 28 kDa CaBP was present in all kidneys from the eleventh week of gestation. At that stage, all deep parts of collecting ducts were homogeneously stained and a few distal tubules located in the deep cortex were intensely labeled. No labeling was observed in the early stage of nephron differentiation (S-body). 28 kDa CaBP distribution changed with kidney maturation. There was a progressive reduction of the deep part of collecting duct labeling and a concomitant increase in the number and intensity of stained distal tubular cells. At the ultrastructural level, 28 kDa CaBP was observed in the cytosol and the nuclear euchromatin. Our study demonstrates the early cellular synthesis of 28 kDa CaBP and its transient expression by deep collecting duct cells during early fetal life, at a time when only a few distal convoluted tubular cells synthetize it.

Adult↗
PubMed1987

Ontogenesis of angiotensin-I converting enzyme in human kidney.

The kidney distribution of angiotensin-I converting enzyme (ACE) was studied in 14 fetuses (11 to 30 weeks old) and 7 children (2 days to 13 years old) by immunohistochemistry using specific antibodies to human kidney ACE. Immunohistochemical techniques included indirect immunofluorescence on cryostat sections of frozen tissue, immunoperoxidase and immunofluorescence of fixed tissue embedded in Paraplast, and immunoelectron microscopy. The ACE distribution in the fetal kidneys was independent of the age of the fetus. ACE was detected in two locations: 1) on the basolateral membranes and primary apical microvilli of epithelial cells from early differentiating proximal tubules; the labeling was intense in brush borders of fully developed proximal tubules; and 2) on glomerular endothelial cells; cells were lined by reaction product as soon as capillaries invaded the inferior cleft of the S-shaped body. Tubular ACE distribution was identical in the postnatal kidneys. The staining of the glomerular endothelium was extremely inconstant. The presence of ACE in proximal tubular cells and glomerular endothelial cells at the beginning of nephron differentiation may indicate that it is involved in the development of nephron function and renal hemodynamic.

Adolescent↗
PubMed1979

[Complement and nephritic activity in membranoproliferative glomerulonephritis].

A study of complement profiles and of "nephritic activity" (NeF activity) has been carried out in 33 children presenting with membranoproliferative glomerulonephritis (MPGN), in order to determine the pathway of complement activation. By morphological studies two varieties of MPGN have been distinguished. In MPGN with subendothelial deposits, immunofluorescent studies and complement profiles show an activation by the classical pathway. The demonstration of NeF activity in 7 of 20 patients suggests that there is recruitment of the amplification pathway. In MPGN with dense deposits, immunopathological studies indicate an activation of the complement system through the alternate pathway, NeF activity being present in 10 of 13 patients. With the functional tests used, it is not possible to ascertain that the factors responsible for the NeF activity in MPGN with subendothelial deposits are identical to the C3NeF identified in MPGN with dense deposits and/or partial lipodystrophy.

Capillaries↗
PubMedDate not supplied

Complement activation in acute glomerulonephritis in children.

Serial determinations of complement components (C1q, C4, C3, C5 and factor B) were performed in 32 children with acute glomerulonephritis. Low levels of C3 were found in 30 patients and low levels of C5 in 26. The findings of reduced C1q and/or C4 levels (25 patients) in the first days of the disease suggest activation of the classical pathway. Depressed Factor B levels were found rarely (4 patients). In all patients, the presence of a C3 splitting activity and/of a C3 nephritic factor-like activity was investigated. Both activities were demonstrated in 7 patients whereas in another patient, only C3 splitting activity was noted. A disappearance of both activities was observed in all patients. In 3 patients tested, the C3 nephritic factor-like activity was heat-labile and was therefore not related to true C3 nephritic factor. Both pathways are implicated in the early phases of the disease but continued C3 depression is probably through alternate pathway.

Acute Disease↗