References of "Nusgens, Betty"
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See detailSkin Fibroblasts Enhance The Tumorigenicity of Human Neoplastic-Cells Transplanted Subcutaneously into Nude-Mice
Simon, N.; Noël, Agnès ULg; Nusgens, Betty ULg et al

in Abstracts for the 1992 Annual Meeting of the European Society for Dermatological Research (1992)

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See detailEffect of cell-cell and cell-matrix interactions on the response of fibroblasts to epidermal growth factor in vitro. Expression of collagen type I, collagenase, stromelysin and tissue inhibitor of metalloproteinases.
Colige, Alain ULg; Lambert, Charles ULg; Nusgens, Betty ULg et al

in Biochemical Journal (1992), 285 ( Pt 1)

Investigations of the effect of epidermal growth factor (EGF) on the expression of four genes involved in the turnover of the extracellular matrix, collagen type I, collagenase, stromelysin and tissue ... [more ▼]

Investigations of the effect of epidermal growth factor (EGF) on the expression of four genes involved in the turnover of the extracellular matrix, collagen type I, collagenase, stromelysin and tissue inhibitor of metalloproteinases (TIMP) were performed on four strains of skin fibroblasts in vitro. Addition of EGF to subconfluent cultures for increasing periods of time up to 5 days induced an inhibition of procollagen alpha 1(I) mRNA and a strong stimulation of collagenase (100-fold) and stromelysin (1000-fold) mRNAs, whereas the mRNA of TIMP was increased to a lesser extent (5-fold). After a 40 h pulse with EGF, these effects persisted for 24-48 h after withdrawal of the growth factor and slowly diminished thereafter to attain control values after several days. By culturing fibroblasts for increasing periods of time, different levels of confluence were obtained allowing for the deposition of an extracellular biomatrix. The steady-state level of collagenase and stromelysin mRNAs were profoundly depressed in confluent as against non-confluent cultures, whereas no major change for TIMP and procollagen alpha 1(I) mRNAs was observed. Upon treatment of these cultures with EGF for 48h, the steady-state level of collagenase, stromelysin and TIMP increased, whereas procollagen alpha 1(I) mRNA was slightly reduced. These modifications were, at least in part, dependent upon a regulation of the transcription rate, as suggested from run-off experiments. Similar states of confluence were obtained by seeding cells at increasing densities in short-term cultures in which cell-cell contact predominated. In such culture conditions, the collagenase and stromelysin mRNAs were enhanced in high as compared to low density cultures. The response to EGF was progressively decreased for collagenase, stromelysin and, to a lesser extent, TIMP mRNAs at most densities and a complete lack of response to EGF at the highest cell density was observed. Under all culture conditions the modulation of collagenase mRNA was paralleled by similar modifications of enzyme activity. These results emphasize the importance of the cell-cell contacts and cell-matrix interactions in the expression of the genes coding for metalloproteinases or their inhibitor and their modulation by growth factors. [less ▲]

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See detailAltered Response of Progeria Fibroblasts to Epidermal Growth Factor
Colige, Alain ULg; Nusgens, Betty ULg; Lapiere, ChM

in Journal of Cell Science (1991), 100((Pt 3)), 649-55

The Hutchinson-Gilford syndrome (progeria) is a rare disorder in childhood characterized by premature and accelerated aging. This study reports the effect of a potent growth factor, EGF, on the ... [more ▼]

The Hutchinson-Gilford syndrome (progeria) is a rare disorder in childhood characterized by premature and accelerated aging. This study reports the effect of a potent growth factor, EGF, on the proliferative capacities and extracellular matrix macromolecules and collagenase expression of two strains of progeria skin-derived cells. At low population doubling levels (PDL less than 10), confluent cultures of progeria fibroblasts made quiescent by lowering the concentration of serum in the medium did not respond to EGF while the mitotic activity of normal PDL-matched fibroblasts was almost maximally restored upon addition of EGF. No obvious difference between normal and low PDL progeria fibroblasts was observed in the number and in the affinity of the receptors measured by [125I]EGF binding. The synthesis of collagen and non-collagen proteins was similar in normal and affected cells at low and high serum concentration and both types of cells responded to EGF by a specific inhibition of collagen synthesis. Besides a normal level of mRNA coding for type I and type III collagens, collagenase and laminin, progeria fibroblasts expressed a high level of elastin and type IV collagen mRNA. Like normal fibroblasts, progeria cells responded to EGF by a decrease in the level of mRNA for fibrillar collagens and elastin. In contrast, a complete lack of response to EGF was observed for collagenase mRNA whereas the expression of this enzyme was strikingly induced by EGF in normal PDL-matched cells. The abnormal expression of type IV collagen was not significantly modified by EGF. At PDL greater than 10, progeria cells exhibited features of senescence. A significant reduction of collagen synthesis was observed and no further inhibition by EGF was recorded. [less ▲]

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See detailInvasion of Reconstituted Basement Membrane Matrix Is Not Correlated to the Malignant Metastatic Cell Phenotype
Noël, Agnès ULg; Calle, A.; Emonard, H. et al

in Cancer Research (1991), 51(1), 405-14

Interactions between tumor cells and basement membranes represent a critical step in the progression of neoplasia and in the metastatic process. Reconstituted basement membrane matrix, matrigel, has been ... [more ▼]

Interactions between tumor cells and basement membranes represent a critical step in the progression of neoplasia and in the metastatic process. Reconstituted basement membrane matrix, matrigel, has been recently used with the aim of developing an in vitro assay of tumor cell invasiveness. We have extended these studies by comparing the invasiveness of a large series of normal and malignant epithelial and mesenchymal cells of human and animal origin cultured on matrigel. Normal cells (fibroblasts, glomerular mesangial cells, keratinocytes), human fibrosarcoma cells (HT1080), and reticular sarcoma cells (M5076) clearly established invasive capabilities in the matrix. However, all the other tested cell lines, malignant or virally transformed cells invasive in vivo (MCF7, T47D, SA52, SW613, MO4, A431, BeWo), as well as normal nontransformed cells (MOH22) were incapable of penetration. The morphological features of matrigel invasion by normal fibroblasts and HT1080 cells are described at the light and electron microscope levels. The extent of degradation of a radiolabeled matrigel is minimal and similar in several cell lines reported to be noninvasive or invasive in vivo. Our data suggest that matrigel does not provide a universal model to correlate the invasiveness of cells in vivo and in vitro. [less ▲]

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See detailAbnormal gene expression in skin fibroblasts from a Hutchinson-Gilford patient.
Colige, Alain ULg; Roujeau, J. C.; De la Rocque, F. et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (1991), 64(6), 799-806

We had the opportunity to investigate a new case of Hutchinson-Gilford progeria, a rare disease commonly regarded as a model in the study of aging. Two strains of fibroblasts (strains 1 and 2) were ... [more ▼]

We had the opportunity to investigate a new case of Hutchinson-Gilford progeria, a rare disease commonly regarded as a model in the study of aging. Two strains of fibroblasts (strains 1 and 2) were derived from two pieces of a skin biopsy. These two populations multiplied as normal cells at low population doubling level but senesced rapidly and stopped proliferating after 14 or 15 population doubling levels. Interestingly, an unusual pattern of growth in clusters was observed for strain 1. The level of collagen and noncollagen protein synthesis of both strains of affected fibroblasts was similar to that of normal fibroblasts as determined by [3H]proline incorporation measurement and was similarly affected by varying serum concentrations. The pattern of the main types of newly synthesized collagen polypeptides analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was similar in normal and progeria cells. The steady-state level of mRNAs coding for macromolecules of the extracellular matrix did not provide any differences between affected and control fibroblasts except for a strong increase of elastin and of alpha 1 and alpha 2 type IV procollagen mRNA mainly in strain 1 and less marked in strain 2. Interestingly, senescent progeria fibroblasts exhibited a reduced level of all the tested mRNAs, whereas collagen type IV and elastin mRNAs remained elevated. As suggested by immunofluorescence and immunoblotting studies, the increased amount of type IV mRNAs was paralleled by an enhanced production of type IV collagen by fibroblasts in vitro. Histologic examination of the skin revealed a superabundant network of abnormal elastic fibers in the reticular dermis and a thickening of basement membranes. The relationship between these alterations and aging in progeria is discussed. [less ▲]

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See detailResponse to Epidermal Growth Factor of Skin Fibroblasts from Donors of Varying Age Is Modulated by the Extracellular Matrix
Colige, Alain ULg; Nusgens, Betty ULg; Lapiere, ChM

in Journal of Cellular Physiology (1990), 145(3), 450-7

The present study was undertaken to investigate the effect of epidermal growth factor (EGF) on the biosynthetic activity of skin fibroblasts from donors of varying age and the modulation of their response ... [more ▼]

The present study was undertaken to investigate the effect of epidermal growth factor (EGF) on the biosynthetic activity of skin fibroblasts from donors of varying age and the modulation of their response to this growth factor by culture in a three-dimensional extracellular matrix. When cultured in monolayer on plastic or at the surface of a collagen gel, EGF specifically inhibited collagen synthesis whatever the age of the donor (from 17 to 84 years, n = 11). This inhibition was paralleled by a significant decrease in the steady-state level of procollagen type I mRNAs. When embedded in a three-dimensional floating collagen lattice, EGF stimulated the non-collagen protein (NCP) synthesis in fibroblasts from younger donors (5 out of 6) while fibroblasts from the older ones were not affected. Collagen production by fibroblasts from younger donors was not inhibited as in monolayer (some being even stimulated) while that of the older donors was inhibited as observed in monolayer. The steady-state level of procollagen type I mRNA was not modified by EGF in the three-dimensional culture. No significant difference was observed in the affinity and the number of EGF receptors of the fibroblasts on plastic or embedded in a collagen lattice between young and aged donors. Our results suggest that the environment of the cells can modulate the reactivity to EGF and reveal differences related to in vivo aging. [less ▲]

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See detailLaminin and Type Iii Procollagen Peptide in Human Preovulatory Follicular Fluid
Christiane, Y.; Demoulin, A.; Gillain, D. et al

in Fertility and Sterility (1988), 50(1), 48-51

The levels of laminin P1 fragment, a marker of basement membrane, and of the aminoterminal sequence of type III procollagen, a marker of interstitial connective tissue, were measured in human preovulatory ... [more ▼]

The levels of laminin P1 fragment, a marker of basement membrane, and of the aminoterminal sequence of type III procollagen, a marker of interstitial connective tissue, were measured in human preovulatory follicular fluids. The concentrations of these peptides correlated with progesterone levels but not with those of estradiol or testosterone. Immunocytochemical studies confirmed the remodeling of the perifollicular basement membrane and interstitial matrix during oocyte maturation. The studies suggest that monitoring of the ovarian connective tissue macromolecules could be useful for estimating follicular maturation. [less ▲]

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See detailAntagonistic Effects of Laminin and Fibronectin in Cell-to-Cell and Cell-to-Matrix Interactions in Mcf-7 Cultures
Noël, Agnès ULg; Calle, A.; Emonard, H. et al

in In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association (1988), 24(5), 373-80

During morphogenesis, tumor progression and metastasis, cell adhesion, dissociation, and migration result from a complex balance between cell-to-cell and cell-to-matrix interactions. Two different ... [more ▼]

During morphogenesis, tumor progression and metastasis, cell adhesion, dissociation, and migration result from a complex balance between cell-to-cell and cell-to-matrix interactions. Two different organization patterns of MCF-7 cells were induced by different extracellular matrix proteins. When plated on plastic or polymeric type I collagen gel used as a model of interstitial matrix, MCF-7 cells spread and grew in monolayer. When cultured on a solid gel of basement membrane (BM) proteins (85% laminin) used as a model of BM, cells formed clusters attached to the matrix. Matrix proteins regulated these two types of cell organization by preferentially promoting cell-to-cell or cell-support interactions. On plastic in the presence of soluble laminin or on laminin-coated dishes, cells also formed clusters. Addition of soluble fibronectin induced spreading of the cells, suggesting that laminin and fibronectin have competitive antagonistic effects on MCF-7 cell morphology. Antilaminin antibodies inhibited cluster formation and attachment, emphasizing the important role of this glycoprotein not only in promoting cluster attachment but also in cell-to-cell contact formation. Such effects of extracellular matrix proteins could play significant roles in tumor progression and metastasis. [less ▲]

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See detailFibroblasts Induce the Assembly of the Macromolecules of the Basement Membrane
Delvoye, Pierre ULg; Piérard, D.; Noël, Agnès ULg et al

in Journal of Investigative Dermatology (1988), 90(3), 276-82

The mechanism regulating the deposition of basement membrane components (BMCs) in a polymeric structure at the junction with the connective tissues is not yet understood. Cultures and cocultures of ... [more ▼]

The mechanism regulating the deposition of basement membrane components (BMCs) in a polymeric structure at the junction with the connective tissues is not yet understood. Cultures and cocultures of epithelial BMC-producing cells (L2 or PER cells) and fibroblasts were prepared in several experimental conditions and the organization of BMCs was studied by immunofluorescence. The pattern of BMCs in pure cultures of L2 or pulmonary epithelial rat (PER) cells consisted of intra- and extracellular granular deposits. At very high density, the cell contours were also underlined by a disrupted network of BMC deposits. A different fibrillar plexus--containing laminin, collagen type IV, and heparan-sulfate proteoglycan resistant to deoxycholate treatment and distant from the cell membrane--was observed in cocultures of L2 or PER cells with fibroblasts. Fibrils of fibronectin and/or collagen type I were most often dissociated from this plexus of BMCs. Similar results were obtained by adding a conditioned medium of L2 or PER cells to confluent fibroblasts, even when the cells were killed. Pure laminin also bound to the fibroblast layer. A coated film of fibronectin or polymeric collagen type I was unable to bind BMC provided by a conditioned medium. It is suggested that molecule(s) synthesized by fibroblasts and deposited in the pericellular matrix are involved in the assembly of BMCs. [less ▲]

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See detailEffect of Egf on Human Skin Fibroblasts Is Modulated by the Extracellular Matrix
Colige, Alain ULg; Nusgens, Betty ULg; Lapiere, C. M.

in Archives of Dermatological Research (1988), 280(Suppl), 42-6

The aim of this work was to clarify the reason why a discrepancy exists between the effects of epidermal growth factor (EGF) on fibroblasts in culture repressing collagen biosynthesis and in vivo ... [more ▼]

The aim of this work was to clarify the reason why a discrepancy exists between the effects of epidermal growth factor (EGF) on fibroblasts in culture repressing collagen biosynthesis and in vivo stimulating wound healing. The effect of EGF on the biosynthetic activity of fibroblasts was measured in various conditions of cultures: on plastic, on plastic coated with various macromolecules of the extracellular matrix, on top of a type I collagen gel, and within a three-dimensional collagen lattice. While the noncollagen protein (NCP) synthesis was not affected by the interactions of the cell with the various coated matrices, collagen synthesis was inhibited. At the surface of a collagen gel, protein synthesis was reduced, while collagen synthesis and degradation were slightly stimulated. When embedded in a lattice, the overall biosynthetic activity of fibroblasts was largely depressed. The addition of EGF to cultures on plastic and on the various coated macromolecules resulted in a further repression of collagen synthesis while cell multiplication was slightly stimulated. On the contrary, the addition of EGF to fibroblasts in a collagen lattice resulted in a stimulation of both NCP and collagen synthesis as observed in vivo. These opposite effects of EGF in a two- or three-dimensional culture system are not related to modification in number or affinity of the EGF receptors at the cell surface. These results further support the similarity in the state of differentiation of fibroblasts in a three-dimensional lattice and in vivo. [less ▲]

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See detailModulation of tumor cell-fibroblasts interactions by 2 extracellular-matrix glycoproteins - laminin and fibronectin.
Noël, Agnès ULg; Nusgens, Betty ULg; Foidart, Jean-Michel ULg et al

in Abstracts for the 18th Annual Meeting of the European Society for Dermatologic Research (1988)

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See detailInfluence of various human-tumor cell-lines on collagen-synthesis by normal fibroblasts
Noël, Agnès ULg; Nusgens, Betty ULg; Foidart, Jean-Michel ULg et al

in Abstracts for the 18th Annual Meeting of the European Society for Dermatologic Research (1988)

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See detailReconstituted basement-membrane matrix modulates fibroblast activities in vitro
Emonard, H.; Grimaud, J. A.; Nusgens, Betty ULg et al

in Journal of Cellular Physiology (1987), 133(1), 95-102

Cellular growth and collagen biosynthesis were compared in dermal calf fibroblasts cultured on plastic or on a reconstituted basement membrane gel, termed matrigel. This matrix, extracted from Engelbreth ... [more ▼]

Cellular growth and collagen biosynthesis were compared in dermal calf fibroblasts cultured on plastic or on a reconstituted basement membrane gel, termed matrigel. This matrix, extracted from Engelbreth-Holm-Swarm tumors, consists mainly of laminin, entactin, type IV collagen, and heparan sulfate proteoglycan. The multiplication rate of fibroblasts grown on matrigel was stimulated compared to that of monolayered cells cultured on plastic, and these cells formed multilayers after 4 days. Protein and collagen biosynthesis was reduced in fibroblasts cultured on matrigel. A higher proportion of the newly synthesized collagen (40%) was incorporated to the extracellular matrix in cultures grown on matrigel than in those grown on plastic (14%). Type III collagen was the preferential collagen type deposited on matrigel, and the ratio of type III:type I collagens secreted in the medium was also slightly higher in cultures grown on matrigel. Partially processed collagen was more abundant in fibroblasts grown on matrigel than in cells cultured on plastic. Finally, cells grown on matrigel exhibited a higher catabolic activity than cells grown on plastic. In this experimental model, the reconstituted basement-membrane matrix seems to influence the activities of fibroblasts significantly. [less ▲]

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See detailModulation of The Biosynthetic Activity of Human-Skin Fibroblasts by Tumor-Cells
Noël, Agnès ULg; Nusgens, Betty ULg; Foidart, Jean-Michel ULg et al

in Abstracts for the 17th Annual Meeting of The European Society for Dermatological Research (1987)

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See detailAntibodies to laminin in preeclampsia.
Foidart, Jean-Michel ULg; Hunt, J.; Lapière, C. M. et al

in Kidney International (1986), 29(5), 1050-57

Laminin is a large basement membrane glycoprotein localized in the trophoblast, glomerular basement membrane and in the mesangial matrix of human glomeruli. It promotes the attachment of epithelial cells ... [more ▼]

Laminin is a large basement membrane glycoprotein localized in the trophoblast, glomerular basement membrane and in the mesangial matrix of human glomeruli. It promotes the attachment of epithelial cells to basement membrane collagen. We have found that 14 sera from 52 patients with severe preeclampsia or eclampsia contain IgG and IgM antibodies which react with placental and kidney basement membranes. These antibodies were specific for laminin and did not react with other basement membrane proteins. They were able to fix complement. They have been demonstrated by radial immunodiffusion, radioimmunoassay and immunofluorescence blocking studies. In primary cultures they were shown to impair the attachment of trophoblast cells to basement membrane collagen. High levels of circulating immune complexes were detected only in sera from preeclamptic patients with circulating antibodies to laminin. The auto-antibodies to laminin could play a major role in the pathogenesis of severe preeclampsia by impairing the attachment of trophoblast cells to placental basement membranes and by fixation to the glomerular basement membranes and mesangial matrix. [less ▲]

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See detailSynthesis of basement membrane components by differentiated thyroid cells.
Wadeleux, P.; Nusgens, Betty ULg; Foidart, Jean-Michel ULg et al

in Biochimica et Biophysica Acta (1985), 846(2), 257-64

Morphological studies indicate that basement membrane formation or maintenance can be achieved in cultures of thyroid cells. In the present investigation we have studied the biosynthesis of this ... [more ▼]

Morphological studies indicate that basement membrane formation or maintenance can be achieved in cultures of thyroid cells. In the present investigation we have studied the biosynthesis of this extracellular matrix by differentiated porcine thyroid cells in culture. They were prepared by two procedures: (1) thyroid cells isolated by dispase digestion of the thyroid gland were maintained in serum-free medium on poly(L-lysine) coated dishes; (2) thyroid follicles released by collagenase treatment of the gland were isolated by differential filtration and cultured in suspension on agarose-coated dishes. In both cases, functional follicular-like structures were obtained as shown by their ability to organify Na125I and to respond to thyrotropin stimulation (250 microU/ml). After incubating the cells with radiolabeled proline or methionine, collagen synthesis was observed with the two types of culture, as shown by the formation of radioactive hydroxyproline and by the synthesis of peptides with electrophoretic properties identical to those of authentic collagen molecules and susceptible to collagenase. Besides variable amounts of type I and type III collagen-like peptides, significant proportions of labeled peptides migrated with type IV collagen chains and were precipitated by anti-type IV collagen antibody; thyrotropin had no significant effect either on the total collagen synthesis or on the relative amounts of the different collagen peptides. When thyroid cells were incubated with [35S]sulfate, a labeled glycosaminoglycan with chromatographic properties analogous to that of heparan sulfate could be obtained in both culture conditions; here again, no effect of thyrotropin was observed. The ability of differentiated porcine thyroid cells to synthesize basement membrane was suggested by their production of type IV collagen and heparan sulfate, two of its potential components. Thyrotropin, which drastically enhanced the functional property of the cells, did not seem to regulate this synthesis. [less ▲]

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See detailAortic collagen biosynthesis during renal hypertension, pregnancy and hypertension during pregnancy in the rat.
Foidart, Jean-Michel ULg; Rorive, Georges ULg; Nusgens, Betty ULg

in Biomedicine (1978), 28(4), 215-9

The synthesis and deposition of collagen and other proteins has been measured in the aorta of the rat by radiolabeling in short term organ culture. Under these conditions, the synthesis of collagen and ... [more ▼]

The synthesis and deposition of collagen and other proteins has been measured in the aorta of the rat by radiolabeling in short term organ culture. Under these conditions, the synthesis of collagen and other proteins is linear for at least five hours. Autoradiography demonstrates a labeling in all cell layers and protein deposition in the extracellular matrix. Hypertension was induced by renal ischemia using Goldblatt's technique. The synthesis and deposition of collagen was stimulated in aorta from the first week of hypertension and in pregnancy, and was even more increased in hypertensive pregnant animals. Reserpine suppresses the rise in blood pressure in operated animals and prevents these modifications. [less ▲]

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See detailThe relationship between blood pressure and aortic collagen metabolism in renal hypertensive rats.
Foidart, Jean-Michel ULg; Rorive, Georges ULg; Nusgens, Betty ULg et al

in Clinical Science and Molecular Medicine (1978), 4

1. Biosynthesis and deposition of collagen, as well as DNA and total proteins, are increased in aortae of rats after 1, 3 and 6 weeks of hypertension. 2. The maximal increase in the rate of synthesis of ... [more ▼]

1. Biosynthesis and deposition of collagen, as well as DNA and total proteins, are increased in aortae of rats after 1, 3 and 6 weeks of hypertension. 2. The maximal increase in the rate of synthesis of collagen is observed within one week of hypertension when the stress to the arterial wall is maximal. 3. Reserpine administration prevents hypertension and inhibits the increase of collagen metabolism. 4. At any time of evolution of the hypertension, a linear positive correlation is found between the collagen content in the aorta and the level of blood pressure. 5. These data suggest that synthesis of matrix components by the arterial smooth-muscle cells is controlled by variation in the blood pressure level and is not a direct consequence of circulating humoral factors liberated by the ischaemic kidney. [less ▲]

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