106 results on '"J D, Sraer"'
Search Results
2. Dexamethasone increases preproparathyroid hormone messenger RNA in human hyperplastic parathyroid cells in vitro
- Author
-
F. Delarue, R. Lacave, J.-M. Garel, A. El M'selmi, M.-N. Peraldi, E. Rondeau, J. D. Sraer, and V. Jousset
- Subjects
medicine.medical_specialty ,Amanitins ,Time Factors ,Clinical Biochemistry ,Parathyroid hormone ,In Vitro Techniques ,Biology ,Binding, Competitive ,Biochemistry ,Dexamethasone ,Parathyroid Glands ,Receptors, Glucocorticoid ,Glucocorticoid receptor ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Northern blot ,Protein Precursors ,Messenger RNA ,Hyperparathyroidism ,Hyperplasia ,General Medicine ,Parathyroid chief cell ,medicine.disease ,In vitro ,Mifepristone ,Endocrinology ,Gene Expression Regulation ,Parathyroid Hormone ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
To determine if parathyroid hormone release in man is directly stimulated by glucocorticoids, dispersed human parathyroid cells from hyperplastic glands obtained from eight renal transplant recipients were studied in vitro. Dexamethasone (10(-11) to 10(-6) mol l-1) increased PTH release in a time- and dose-dependent manner. A plateau was reached at 10(-8) mol l-1 (1015 +/- 149 vs. 230 +/- 27 pg 10(-4) cells for control value, after 24 h incubation; P less than 0.0001). An interaction with a glucocorticoid receptor was suggested since 10(-6) mol l-1 RU 486 blunted the dexamethasone-induced PTH release. By Northern blot analysis, dexamethasone was found to increase the amount of preproPTH mRNA in these cells. The effect of dexamethasone was probably at the gene level since (1) 1,25 dihydroxy vitamin D3 inhibited both iPTH and preproPTH mRNA increases induced by dexamethasone and (2) alpha-amanitin (1,25 micrograms ml-1) also completely suppressed the dexamethasone-induced PTH release. Thus, for the first time, we demonstrate that dexamethasone induces an increase of PTH synthesis, probably by increasing PTH gene transcription. This effect may play an important pathogenic role in persisting hyperparathyroidism and steroid-induced bone complications in renal transplant recipients.
- Published
- 2008
3. Biopsy as a Guide in the Treatment of �Medical� Acute Renal Failure
- Author
-
Gabriel Richet, P. Duhoux, Liliane Morel-Maroger, J. D. Sraer, A. Kanfer, and O. Kourilsky
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Biopsy ,Medicine ,Radiology ,business - Published
- 2015
4. Abstracts of papers and posters safe handling of medicines
- Author
-
H. -J. Meyer, Th(Dick) F. J. Tromp, E. Kleijn, Suzanne M. Fields, J. P. P. Moors, H. Enlund, D. K. Luscombe, J -Ph Remond, S. Martv, S. Dhillon, D. Taylor, A. Kostrzewski, B. M. Bluml, M. L. Enlow, S. E. Metzler, Philip A. Vries, C. J. Duty, H. Y. Lee, Tibor Ábrahám, A. A. Cardoni, J. Sýkora, S. Szücsová, J. -Ph Reymond, S Marty, D. Engová, J. Sheridan, J. Vlček, D. G. Webb, I. P. Bates, A. Tabachnik, Y. Cass, J. Jacobs, A. Vexler, R. Gorodetsky, C. M. C. Whittlesea, R. Walker, F. Khan, J. Houghton, I. Phillips, J. Szymura-Oleksiak, A. Wasieczko, E. Wyska, I. Ayani, M. F. Errecalde, J. M. Rodriauez-Sasiain, C. Aouirre, Medall M. D. Bellés, Alos V. G. Casabó, Botella M. A. Hervás, Pérez A. Cabrera, Torres N. V. Jiménez, Melchor D. E. Casterá, Gimeno F. J. Abad, J. E. Clark, E. C. Gomez, A. C. Cruz, R. L. Wilbur, I. Alfonso, C. H. Grout, R. Goldstein, P. Rivers, K. Stutz, S. Mühlcbach, George Udeani, Irene Zervopoulous, Krishna Patel, Michael Mullane, R. Radziwill, J. Dudek, U. Herbst, J. Bency, P. Muff, S. Marty, J. -Ph Rcymond, M. D. Aumente, M. D. Panadero, J. M. Latre, M. Torres, M. J. Villegas, J. Alvarez, E. A. Dijk, E. M. Logman, B. Ploeger, T. G. Schors, D. J. Steensma, A. Langlois-Karaga, A. Davignon, M. Bues-Charbit, V. Somme, J. Albanese, O. Durbec, C. Martin, N. Morati, G. Balansard, M. E. Araújo Pereira, A. Nogueira, J. C. Silva, I. Mega, A. Gomes Costa, J. A. Morais, M. M. Prata, G. Cajaraville, M. J. Tamés, B. García, Marqucs F. J. Batel, H. S. Capela, P. Pomingues, J. A. Feio, C. Siha, K. Wolter, E. Fritschka, H. Schneesann, A. Stuurman, A. Gudjonsdottir, H. R. Angelo, M. Rasmuassen, S. N. Rasmussen, J. Carrera, A. Idoate, A. Modrego, I. Tejedor, J. Giráldez, M. A. Mangues, R. Farré, X. Demestre, G. Ginovart, J. Orozco, G. Julio, M. A. Moral, C. Busin, C. Bardin, C. Seroux, H. Sauvageon-Martre, J. -D. Sraer, F. Chast, J. V. Real, M. Climente, I. Font, C. Pérez, J. P. Ordovás, M. Hermenegildo, J. L. Catalán, J. Juan, N. V. Jiménez, F. Amiot, S. Clavel, B. Sarrut, C. Doreau, F. Zs Hips, Gy Soós, G. Petô-Nagy, Z. Vincze, H. Robays, A. Freidank, A. Fischer, H. Cordovilla, B. Font, A. Ortega, M. S. Salek, S. Thomas, A. J. Baver, J. Vandenbroucke, A. Ekedahl, K. Tuovinen, K. Wallenius, A. W. Boeke, E. J. Veenstra, M. A. P. C. Poll, K. Nonkes, I. Carlen, M. Tanner, C. Reinke, J. Escher, J. Fischer, S. Marly, G. K. Ooi, A. Cottle, A. Savage, E. Temesvári, M. C. Montero, M. Pastor, M. L. Valdivia, C. Buenestado, A. Lluch, M. Atienza, B. Santos, Roca M. Echeverria, Gallastegui S. Fernandez, Rizaldos C. Alonso, Trueba M. D. Arce, C. D. Booth, A. Aldaz, C. Lacasa, M. Cordovilla, V. Alzina, J. L. Sheridan, B. Usselmann, G. Carstens, A. C. Falcao, M. M. Femández de Gatta, F. Nieto Cobo, A. C. Alonso Gorzátez, J. M. Lanao, A. Dominguez -Gil, A. Burr, M. P. Ferreira, M. O. Rodrigues, M. E. Pereira, M. F. Marques, M. C. Vicente, A. P. Carrondo, M. A. Pires, M. A. Granja, L. Tuneu, J. Serna, E. Saló, P. Cerutti, P. Cardona, J. Bonal, D. G. Cosh, F. Abbott, C. P. Alderman, F. W. Mav, P. G. Peters, S. D. Scott, D. Jenkins, C. Cairns, N. D. Barber, S. M. Cammie, A. J. Burr, I. Brännström, P. Giner Boya, C. Parreño Aliaga, M. M. Negredo González, L. Lorente Mansilla, V. Pidrman, Z. Fendrich, C. Alberola, B. Castillo, C. Girón, A. Morell, C. López-Calull, L. Carcia-Capdevila, M. Sanz, D. Cardona, I. Castro, R. Saura, J. M. Pérez, Eva Johnsen, Ole Krogsgård, R. L. Pinheiro, I. A. Morais, Marques F. J. Batel, P. Domingues, C. Silva, C. L. L. Astdrager, T. Schnlekamp, J. J. Gier, C. W. H. Rutten, M. C. Rivera, M. Vilanova, I. Mattei, and A. Roglan
- Subjects
Pharmacology ,business.industry ,medicine ,Pharmaceutical Science ,Pharmacology (medical) ,Pharmacy ,General Medicine ,Medical emergency ,Toxicology ,business ,medicine.disease ,Safe handling - Published
- 1993
5. [Hemophagocytosis associated with an Escherichia coli sepsis: a case report]
- Author
-
N, El Khoury, K, Lassoued, G, Pellé, A, Foucher, M-A, Costa, E, Rondeau, and J-D, Sraer
- Subjects
Male ,Histiocytosis, Non-Langerhans-Cell ,Humans ,Bacteremia ,Syndrome ,Macrophage Activation ,Escherichia coli Infections ,Aged - Abstract
Hemophagocytic lymphohistiocytosis syndrome (HLS) is defined by activated macrophage proliferation. These cells phagocyte the blood elements. This syndrome can be primary as an autosomal recessive disease or secondary to neoplasia, immune diseases or infections-viral, parasitary or bacterian.Our case concerns an association of HLS and Escherichia coli (E. coli) sepsis in a metastatic prostatic cancer. The evolution was rapidly improved by antibiotics alone. The clinical and biological aspects as well as the differential diagnosis are discussed.The HLS is fatal. It can be caused by a severe infection, even an E. coli sepsis. The treatment focused on etiology can be sufficient.
- Published
- 2003
6. [Should acute kidney failure be treated in people over 80 years of age at an intensive care unit?]
- Author
-
J D, Sraer, K, Akposso, and E, Rondeau
- Subjects
Aged, 80 and over ,Male ,Survival Rate ,Intensive Care Units ,Critical Care ,Age Factors ,Humans ,Female ,Acute Kidney Injury ,Aged - Abstract
This is the first retrospective study aimed to analyze the clinical symptoms, the etiology, the morbidity and the lethality of acute renal failure in patients over 80 years. The criterion of inclusion was the occurrence of acute renal failure defined on the basis of high plasma creatinine associated with normal kidney size in patients of this class of age who had been hospitalized in an intensive care unit between October 1971 and September 1996. In the case of a preexisting moderate nephropathy, acute renal failure was defined by an increase of plasma creatinine of at least 50% over its basal value. Three hundred and eighty-one patients over 80 years out of a total of 2,111 patients with acute renal failure were included in this study. The various etiologies and mechanisms of the disease are described. Twenty-nine% of the patients underwent dialysis. The global lethality reached 40% during the time of hospitalization. The factors significantly associated with a poor prognosis were identified as cancer essentially, but also sepsis and preexisting cardiovascular diseases. The mean survival after hospitalization was of 19 months. In summary, the frequency of admission for acute renal failure of patients over eighty in intensive care units is increasing but the rate of lethality observed is less than expected. A pattern of pathological associations leading to death in these patients cannot be defined with certitude. Therefore, the methods of renal replacement therapy available in modern intensive care units must be utilized in this class of age as it is the case in younger patients.
- Published
- 2001
7. Regulation of the paired type IV collagen genes COL4A5 and COL4A6. Role of the proximal promoter region
- Author
-
Y, Segal, L, Zhuang, E, Rondeau, J D, Sraer, and J, Zhou
- Subjects
Base Sequence ,Gene Expression Regulation ,Transcription, Genetic ,Genes, Reporter ,Molecular Sequence Data ,DNA Footprinting ,Humans ,Collagen ,DNA ,Regulatory Sequences, Nucleic Acid ,Promoter Regions, Genetic ,Cell Line - Abstract
Tissue-specific expression patterns of the paired type IV collagen genes COL4A5 and COL4A6 form the basis for organ involvement in X-linked Alport syndrome, a disorder in which these genes are mutated. We investigated the proximal promoter region of COL4A5 and COL4A6 using glomerular visceral epithelial cells, in which COL4A5 alone is transcribed; keratinocytes, in which the genes are co-transcribed; and additional model cell lines. By RNase protection assays, the intergenic region is 292 base pairs. Transcription start sites for two 5' splice variants of COL4A6 are 1 kilobase apart. Transient transfections with reporter gene constructs revealed that the minimal promoters for COL4A5 and COL4A6 are within 100 base pairs of their respective transcription start sites and are functionally distinct. In further transfection, gel shift and footprinting assays, we defined a bidirectional positive regulatory element, which functions in several cell types, but not in glomerular visceral epithelial cells selectively transcribing COL4A5. The existence of separate promoters for COL4A5 and COL4A6 permits fine control over their expression. Activation through the bidirectional element can bring about co-expression of the genes, exploiting their paired arrangement. Features of the proximal promoter region frame its roles in a hierarchy regulating type IV collagen gene expression.
- Published
- 2000
8. [Rapidly progressive acute renal failure. A rare complication of primary Sjogren syndrome]
- Author
-
K, Akposso, H, Martinant de Preneuf, F, Larousserie, J D, Sraer, and E, Rondeau
- Subjects
Glomerulonephritis ,Sjogren's Syndrome ,Humans ,Female ,Acute Kidney Injury ,Middle Aged - Abstract
Renal impairment, usually due to tubulointerstitial and rarely glomerular disorders occurs in 10 to 30% of patients with primary Sjögren's syndrome. Extracapillary proliferation may also be observed.A 62-year-old woman with primary Sjogren's syndrome diagnosed 12 years earlier, developed microscopic polyangeitis leading to rapidly progressive renal failure. Antipolynuclear anticyclosine antibody (ANCA) serology was positive (pANCA, anti MPO) and the renal biopsy evidenced necrotizing glomerulonephrities with extracapillary proliferation. Outcome was favorable despite a recurrence one year after onset.Extracapillary proliferative glomerulonephritis is characterized by hematuria and proteinuria associated with renal failure. Renal impairment may worsen rapidly, sometimes leading to an emergency situation because the renal prognosis is directly related to delay to treatment. This case illustrates an uncommon complication of Sjögren's syndrome, compared with the usual tubulointerstitial disorders. The mechanism remains unknown, but outcome can be favorable with rapidly initiated immunosuppressor treatment.
- Published
- 2000
9. Tacrolimus-induced hemolytic uremic syndrome and end-stage renal failure after liver transplantation
- Author
-
J P, Rerolle, K, Akposso, N, Lerolle, B, Mougenot, T, Ponnelle, E, Rondeau, and J D, Sraer
- Subjects
Hemolytic-Uremic Syndrome ,Humans ,Kidney Failure, Chronic ,Female ,Middle Aged ,Kidney ,Immunosuppressive Agents ,Tacrolimus ,Liver Transplantation - Abstract
Hemolytic uremic syndrome (HUS) is a rare complication in solid organ transplantation. It can be associated with severe hypertension. Several risk factors have been identified including immunosuppressive drugs such as cyclosporin A and, more recently, tacrolimus.Here we report a case of tacrolimus-induced HUS in a 61-yr-old woman after liver transplantation. Hypertension, microangiopathic anemia and end-stage renal failure occurred 2 yr after liver transplantation.At admission, she had malignant hypertension with a severe hypertensive retinopathy, renal failure (creatininemia: 800 micromol/L) and microangiopathic anemia (Hb: 7.3 g/dL, a low platelet count and elevated lactate dehydrogenase). At renal biopsy, histologic findings were ischemic and sclerotic glomeruli with hyaline thrombi, severe mesangiolysis and interstitial fibrosis.Despite steroid treatment, antihypertensive agents and fresh frozen plasma therapy, end-stage renal failure was observed and chronic hemodialysis treatment was required.
- Published
- 2000
10. Hemolytic uremic syndrome. Recurrence after renal transplantation. Groupe Coopératif de l'Ile-de-France (GCIF)
- Author
-
A, Lahlou, P, Lang, B, Charpentier, B, Barrou, D, Glotz, C, Baron, C, Hiesse, H, Kreis, C, Legendre, J, Bedrossian, B, Mougenot, J D, Sraer, and E, Rondeau
- Subjects
Adult ,Male ,Chi-Square Distribution ,Time Factors ,Graft Survival ,Middle Aged ,Kidney Transplantation ,Statistics, Nonparametric ,Actuarial Analysis ,Recurrence ,Risk Factors ,Hemolytic-Uremic Syndrome ,Humans ,Kidney Failure, Chronic ,Female ,Age of Onset ,Retrospective Studies - Abstract
Hemolytic uremic syndrome (HUS) is an uncommon cause of end-stage renal failure in adults, and few data are available concerning the outcome of renal transplantation in these patients. We conducted this retrospective multicentric study to appreciate the outcome of adult renal transplant recipients whose primary disease was HUS. Sixteen patients, transplanted between 1975 and 1995, were included in the study. In each case, initial diagnosis of HUS was documented by a kidney biopsy. These 16 patients received a total of 25 allografts: 1 graft for 9 patients, 2 grafts for 5 patients, and 3 grafts for 2 patients. Nine patients (56%) developed definite clinical and pathologic evidence of recurrence on at least 1 graft. Four additional patients (25%) demonstrated only some clinical or pathologic evidence of recurrence which could not be distinguished from acute vascular rejection. Three patients had no sign of recurrence of the initial disease. The 1-year graft survival rate was 63% and the 5-year graft survival rate was 18.5%. In the group of patients with proven or possible recurrence (n = 13), the 1-year and 5-year graft survival rates were 49% and less than 10%, respectively. The recurrence was an early event, occurring before the end of the first month after transplantation in half the cases. The recurrence rate was 92% in non-nephrectomized patients and 50% in patients with bilateral nephrectomy. In the literature, 71 adult patients with primary HUS had received a total of 90 kidney grafts. Among them, 54% had a recurrence on their graft, which was diagnosed in 52% of the kidney transplants. It is note-worthy that when data from the literature are pooled with our results, the rate of recurrence appears to be significantly lower in binephrectomized patients than in patients with their native kidneys at the time of transplantation (5 of 14 versus 27 of 35 patients, respectively, p = 0.0155). By univariate analysis, no other risk factor for recurrence could be identified. Treatment with cyclosporine A did not influence the recurrence rate. We conclude that recurrence of HUS after renal transplantation is a frequent, early, and severe complication, leading rapidly to graft loss. Prospective studies are needed to confirm that bilateral nephrectomy prior to transplantation decreases the rate of recurrence.
- Published
- 2000
11. Role of thrombin and its receptor, the protease-activated receptor 1, in the pathophysiology of glomerular injury
- Author
-
E, Rondeau, J D, Sraer, G, Nguyen, C J, Hé, U, Zacharias, and Y, Xu
- Subjects
Glomerulonephritis ,Anti-Glomerular Basement Membrane Disease ,Kidney Glomerulus ,Thrombin ,Animals ,Humans ,Receptor, PAR-1 ,Receptors, Thrombin - Published
- 1999
12. [The missions of a Nephrology Department in the year 2000]
- Author
-
J D, Sraer
- Subjects
Hospitals, University ,Nephrology ,Disease Progression ,Humans ,Acute Kidney Injury ,Forecasting - Abstract
The treatment of acute renal failure: 1) Evaluate new methods of dialysis that should be less aggressive than hemodialysis, such as hemodiafiltration, in order to decrease the hemodynamic risks of an elder population. 2) Improve teaching: education of students and of physicians at the University must be more effective to allow a better diagnosis of acute renal failure and therefore its prevention, and a rapid histological examination of renal tissue that constitutes the basis of etiopathogenic treatment of glomerular and/or vascular nephropathies. The treatment of chronic renal failure: 1) Improve and develop the present therapy: automated peritoneal dialysis at home should be developed. 2) The evaluation of new techniques of hemodialysis in the patient can only be undertaken at the University Hospitals. New experimental procedures can endow the artificial kidney with most of the metabolic functions of normal kidney. This method has not been tested yet in men. 3) The xenografts are very interesting approaches because of the lack of organs, however there are major obstacles including insufficient knowledge of the mechanisms of hyperacute graft rejection, of the possibility of transmission of anthropozoonoses from animals to humans, and of gene mutation of virus that usually are not pathogenic in man; finally studies on the adaptation of the xenograft, which possess different biological parameters, to the human milieu, should be considered. 4) Cell therapy or gene therapy are currently under investigation. The major difficulties are to assess that the vector used to transfer the gene is absolutely harmless to man and to restrict the gene delivery to the cells of interest. The molecular genetics determinants should be essential to prevent kidney diseases because they would help in defining the individual susceptibilities to develop nephropathies.
- Published
- 1999
13. [Evidence of a renin receptor on human mesangial cells: effects on PAI1 and cGMP]
- Author
-
G, Nguyen, L, Bouzhir, F, Delarue, E, Rondeau, and J D, Sraer
- Subjects
Iodine Radioisotopes ,Tissue Plasminogen Activator ,Plasminogen Activator Inhibitor 1 ,Renin ,Humans ,Calcium ,Receptors, Cell Surface ,Cyclic GMP ,Recombinant Proteins ,Glomerular Mesangium - Abstract
Most proteases a receptor or a binding site that serves to concentrate the proteolytic activity on the cell surface and to mediate cellular effects. We looked for such a receptor for renin, an aspartyl protease. The binding of recombinant human renin labelled with 125I was studied on primary and immortalized human mesangial cells. The binding of renin was specific, saturable and was characterized by Kd = 0.4 nM and 8,000 sites/cell and Kd = 1 nM and 2,000 sites/cell for primary and immortalized cells, respectively. The binding did not depend on the active site of the enzyme, was not followed by internalization and degradation of renin and did not modify intracellular Ca2+. Stimulation of primary cells with 100 nM induced a significant increase of 3H thymidine incorporation but was not associated with an increase of the cell number. Furthermore, incubation of mesangial cells 24 h with 100 nM renin provoked an increase of tPA and of PAI1 in the conditioned medium. This increase was not modified neither by captopril nor by angiotensin II receptors antagonists. The tPA antigen elevation was confirmed by fibrin zymography showing an increase of tPA/PAI1 complexes. But, surprisingly, the reverse zymogram showed that PAI antigen increase was associated with decreased PAI activity which was due to PAI clivage in an inactive form. PAI clivage by renin required the presence of the cells and could not be obtained by incubating renin and recombinant human PAI alone. When primary mesangial cells were cultured in the presence of a specific inhibitor of renin active site, RO 42-5982, PAI accumulation in the conditioned medium was reduced by 50-60%, suggesting that endogenous renin plays a role in PAI synthesis and/or secretion. The binding of renin does not induce cAMP and cGMP generation. However, in the presence of renin (100 nM and 1 microM) the extent of cGMP generated by CNP (10 and 100 nM) was reduced by 50%. Preliminary results of the renin receptor purification by affinity chromatography indicate that the receptor Mr is about 57 kDa.
- Published
- 1998
14. Long-term outcome of kidney transplantation in patients with systemic lupus erythematosus: a multicenter study. Groupe Cooperatif de Transplantation d'île de France
- Author
-
P, Grimbert, J, Frappier, J, Bedrossian, C, Legendre, C, Antoine, C, Hiesse, M O, Bitker, J D, Sraer, and P, Lang
- Subjects
Adult ,Male ,Middle Aged ,Kidney Transplantation ,Lupus Nephritis ,Treatment Outcome ,Living Donors ,Humans ,Kidney Failure, Chronic ,Lupus Erythematosus, Systemic ,Multicenter Studies as Topic ,Female ,Longitudinal Studies ,Retrospective Studies - Abstract
The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation.The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months.No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others.The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.
- Published
- 1998
15. [Human immunodeficiency virus and acute renal insufficiency]
- Author
-
J D, Sraer and M N, Peraldie
- Subjects
Adult ,Male ,Humans ,Female ,HIV Infections ,Acute Kidney Injury ,Middle Aged ,Retrospective Studies - Abstract
We describe here the broad spectrum of acute renal insufficiency occurring in the course of human immunoinsufficiency virus infection. In our renal unit in Tenon hospital, 90 human immunoinsufficiency virus-infected adult patients were admitted for acute renal insufficiency between June 1988 and December 1996. Sixty out of them had a pathological diagnosis. The remaining patients did not have renal biopsy because of obstructive renal failure (n = 2), bleeding risk (n = 11), or clinically evident hypovolemic and/or sepsis-related acute tubular necrosis (n = 17). Nine different causes of acute renal insufficiency were listed. Human immunoinsufficiency virus-associated nephropathy, the most specific human immunoinsufficiency virus-related renal disease, which was diagnosed in 14 patients, is characterized by focal and segmental glomerulosclerosis with an important hyperplasia and/or proliferation of podocytes and huge tubular distension. The rapid progression to end-stage renal failure was not a constant feature since 10/14 patients had a partial renal recovery. Hemolytic-uremic syndrome was the other major cause of acute renal failure in these patients (32 cases) and was found to be associated with active cytomegalovirus infection. Cytomegalovirus-infected cells were present in half of the renal biopsies performed in this group of patients. Furthermore, these patients had an increased plasma tissue-type plasminogen activator activity whereas its type 1 inhibitor was not significantly increased, as opposed to non human immunoinsufficiency virus-associated hemolytic-uremic syndrome. Half of the patients had a complete renal recovery. The other causes of acute renal insufficiency were 1) intratubular deposition of either drugs (Adiazine, Foscavir, Indinavir) in 13 patients, or monoclonal light chain in one patient with B cell-lymphoma; 2) lupus-like glomerulonephritis characterized in one case by a complete clinical remission after 6 month-treatment by antiproteases; 3) acute tubular necrosis. In this setting, rhabdomyolysis could reveal HIV infection. The heterogeneity of renal diseases could be explained by the variation of human immunoinsufficiency virus-associated infections along time and by the different drugs which permit a better survival. We can hypothesize that new HIV-associated diseases will occur with the long term use of antiproteases.
- Published
- 1998
16. [Role of thrombin and its receptor in the pathogenesis of severe forms of human glomerulonephritis with fibrin deposits]
- Author
-
J D, Sraer and E, Rondeau
- Subjects
Fibrin ,Glomerulonephritis ,Case-Control Studies ,Thrombin ,Humans ,Receptors, Thrombin - Abstract
For the first time, a functional thrombin receptor has been found in human glomeruli by immunohistochemistry using a specific monoclonal antibody directed against extracellular N-terminus. This receptor is constitutively expressed in normal human kidney. The 3 glomerular cell types, endothelial, mesangial and epithelial cells, are positively stained as are the endothelial cells of renal arteries. By in situ hybridization using a digoxigenin-labelled cDNA probe specific for thrombin receptor, the thrombin receptor mRNA was found to have the same distribution. A lighter staining of glomerular endocapillary cells was observed in cases of thrombotic microangiopathy and extracapillary glomerulonephritis. 2 renal diseases associated with in situ thrombin generation and fibrin formation whereas by in situ hybridization, the thrombin receptor mRNA was overexpressed. To understand the discrepancy between the surface expression of thrombin receptor antigen in normal and fibrin-related glomerulopathies, we studied the internalization of thrombin receptor in human mesangial cells. We found that thrombin and thrombin agonist peptides induce homologous internalization of thrombin receptor in a dose-dependent manner. In addition, a dose-dependent loss of cell surface thrombin receptor is induced by phorbol-12-myristate-13-acetate (PMA), suggesting that thrombin receptor undergoes heterologous internalization in response to PMA. The homologous internalization of the thrombin receptor is not mediated by protein kinase C activation. Taken together, the results suggest that thrombin receptor is internalized through at least 2 different pathways.
- Published
- 1996
17. Relationship between alpha-smooth muscle actin expression and fibrotic changes in human kidney
- Author
-
G, Boukhalfa, A, Desmoulière, E, Rondeau, G, Gabbiani, and J D, Sraer
- Subjects
Adult ,Graft Rejection ,Male ,Adolescent ,Antibodies, Monoclonal ,Muscle, Smooth ,Middle Aged ,Kidney ,Fibrosis ,Kidney Transplantation ,Actins ,Mice ,Glomerulonephritis ,Creatinine ,Immunoglobulin G ,Cyclosporine ,Animals ,Humans ,Female ,Child ,Immunosuppressive Agents ,Aged - Abstract
The alpha-smooth muscle (alpha-SM) actin isoform is expressed normally by vascular SM cells and by stromal fibroblastic cells in pathological conditions leading to fibrosis. In order to investigate the relation between kidney fibrosis and alpha-SM actin expression, we studied 51 renal biopsies from 45 patients: 30 with various forms of glomerulonephritis; 1 with acute tubular necrosis; 1 with acute interstitial nephritis, and 13 renal transplant recipients. The presence of alpha-SM actin was examined by using anti-alpha SM-1, a mouse monoclonal antibody (IgG2 alpha) specific for alpha-SM actin. alpha-SM actin scores were estimated semiquantitatively, as were glomerulosclerosis and interstitial fibrosis. In acute tubular necrosis and in well-functioning grafts, alpha-SM actin expression was limited to vascular SM cells. In glomerular diseases, alpha-SM actin expression was upregulated in mesangial area in 25 of 36 biopsies, and even more frequently in the periglomerular and peritubular interstitium (34 of 36 cases, chi 2 = 7.6, P0.01). Whereas glomerular alpha-SM actin expression seemed to decrease as glomerulosclerosis progressed, there was a positive correlation between interstitial alpha-SM actin scores and the degree of interstitial fibrosis. Similarly, interstitial alpha-SM actin expression was found in acutely or chronically rejected kidneys, but not in well-functioning grafts. We conclude that upregulation of alpha-SM actin in the glomerulus indicates mesangial cell activation and is not always correlated with the degree of glomerulosclerosis. In contrast, interstitial upregulation of alpha-SM actin which indicates myofibroblast activation is correlated with the degree of interstitial fibrosis.
- Published
- 1996
18. Integrin-mediated interactions between primary/T-sv40 immortalized human glomerular epithelial cells and type IV collagen
- Author
-
U, Krishnamurti, Y, Chen, A, Michael, Y, Kim, W W, Fan, J, Wieslander, C, Brunmark, E, Rondeau, J D, Sraer, F, Delarue, and E C, Tsilibary
- Subjects
Integrins ,Mice ,Antigens, Polyomavirus Transforming ,Kidney Glomerulus ,Cell Adhesion ,Integrin alpha3beta1 ,Animals ,Humans ,Cattle ,Epithelial Cells ,Collagen ,Cell Line, Transformed - Abstract
The use of human glomerular epithelial cells (HGEC) in research has been severely restricted by several obstacles, which have been circumvented by the generation of T-SV40 immortalized human visceral glomerular epithelial cells (Delarue et al, 1991). In this work, we compared the primary and immortalized HGEC for expression of integrin and some nonintegrin surface receptors. We also studied the adhesion of both types of HGEC to glomerular basement membrane (GBM), type IV collagen (tIV), and its major noncollagenous NC1 domain. The integrins mediating adhesion of HGEC to tIV were also examined. Expression of integrin and some nonintegrin cell surface receptors was analyzed by flow cytometry. Adhesion to GBM, tIV, and its major noncollagenous NC1 domain was studied by direct solid phase cell adhesion assays. Identification of integrins mediating adhesion of HGEC to tIV was achieved by inhibition of cell adhesion using monoclonal antibodies to integrin subunits. The primary and immortalized HGEC share phenotypic characteristics, and alpha3beta1 appeared to be the major integrin present on both HGEC types. The kinetics of binding to GBM, tIV, and its noncollagenous NCI domain were similar in both the primary and immortalized HGEC, although the latter displayed a somewhat weaker binding. Both the primary and immortalized HGEC displayed significantly better adhesion to NC1-alpha3 compared with NC1-alpha1, alpha3beta1 appears to be the major integrin mediating the adhesion of HGEC to tIV. Our studies suggest that alpha3beta1 is the major integrin present on HGEC. This has been confirmed by flow cytometric analysis. In addition, we demonstrated a functional role for this integrin in mediating attachment of HGEC to tIV. Our data also demonstrate a preference in binding of HGEC to alpha3 chains of NC1 compared with alpha1 chains of NC1. These findings were seen in both the primary and immortalized HGEC. The T-SV40 immortalized HGEC can therefore serve as a very useful tool to study glomerular visceral cell biology.
- Published
- 1996
19. [Pumps, channels and transporters of the renal tubule: a growing field of investigation]
- Author
-
P, Ronco, E, Rondeau, and J D, Sraer
- Subjects
Kidney Tubules ,Humans ,Ion Pumps ,Carrier Proteins ,Ion Channels - Published
- 1996
20. Constitutive expression and modulation of the functional thrombin receptor in the human kidney
- Author
-
Y, Xu, U, Zacharias, M N, Peraldi, C J, He, C, Lu, J D, Sraer, L F, Brass, and E, Rondeau
- Subjects
Immunoenzyme Techniques ,Base Sequence ,Molecular Sequence Data ,Humans ,Kidney Diseases ,Receptors, Thrombin ,Amino Acid Sequence ,Kidney ,Polymerase Chain Reaction ,In Situ Hybridization ,Research Article - Abstract
Thrombin exerts procoagulant effects and has also many cellular effects mediated by cell surface receptors. A functional thrombin receptor from human platelets has been cloned and sequenced. In the present study, by reverse transcription and polymerase chain reaction, using specific primers designed from the thrombin receptor cDNA sequence, we show that the mRNA encoding for this receptor can be amplified from freshly isolated human glomeruli obtained by microdissection of normal kidney cortex. By immunohistochemistry using a specific monoclonal antibody, ATAP2, directed against the extracellular N-terminus of this receptor, we find that this functional thrombin receptor is constitutively expressed in the normal human kidney. The three glomerular cell types, endothelial, mesangial, and epithelial cells, were positively stained, as were the endothelial cells of renal arteries, arterioles, venules, and peritubular capillaries. Occasionally, interstitial cells and smooth muscle cells in the media of renal arteries were also stained. Proximal and distal tubular cells were not stained. By in situ hybridization, using a digoxigenin-labeled cDNA probe specific for thrombin receptor, the thrombin receptor mRNA was found to have the same distribution as the thrombin receptor protein detected by immunohistochemistry. A lighter staining of glomerular endocapillary cells was observed in cases of thrombotic microangiopathy and extracapillary glomerulonephritis, two renal diseases associated with in situ thrombin generation and fibrin formation. In one case of thrombotic microangiopathy, we observed an increase in thrombin receptor mRNA. This suggests that thrombin receptor protein is not always correlated with thrombin receptor mRNA level. Internalization and degradation of thrombin receptor protein have been demonstrated in vitro and could also occur after activation in vivo. This is the first demonstration of the constitutive expression of the functional thrombin receptor in the human kidney. These results suggest that thrombin may exert glomerular and vascular effects within the kidney in normal and in pathological conditions.
- Published
- 1995
21. Acquired circulating anticoagulant with anti-factor V activity in AIDS: first case report
- Author
-
A, Denis, C, Baudeau, E, Verdy, R, Couderc, E, Rondeau, and J D, Sraer
- Subjects
Adult ,Male ,Acquired Immunodeficiency Syndrome ,Hemostasis ,Anticoagulants ,Factor V ,Humans ,Immunoglobulins ,Blood Coagulation - Abstract
An acquired circulating anticoagulant with anti-factor V activity appeared in a 29 year old AIDS patient with widespread Kaposi's sarcoma following 21 days of fresh frozen plasma therapy for haemolytic and uraemic syndrome. Residual factor V activity was very low (5% of normal). However, the inhibitor was of low titre (0.5 Bethesda Units/ml), while antigenic factor V levels remained at 100%. Dot blotting with human factor V and polyvalent and specific immunoglobulin antisera showed the antibody to belong to the IgG class. Haemostatic tests in vitro were only partly corrected by addition of washed human platelets and despite transfusion of large amounts of platelets the patient died from massive pulmonary haemorrhage. This would appear to be the first documented case of an anti-factor V inhibitor occurring in an AIDS patient.
- Published
- 1995
22. Heparin selectively inhibits synthesis of tissue type plasminogen activator and matrix deposition of plasminogen activator inhibitor 1 by human mesangial cells
- Author
-
J, Hagège, F, Delarue, M N, Peraldi, J D, Sraer, and E, Rondeau
- Subjects
Heparin ,Enzyme-Linked Immunosorbent Assay ,Blotting, Northern ,Immunohistochemistry ,Proto-Oncogene Mas ,Glomerular Mesangium ,Tissue Plasminogen Activator ,Plasminogen Activator Inhibitor 1 ,Humans ,Tetradecanoylphorbol Acetate ,Heparitin Sulfate ,Microscopy, Polarization ,Cell Division ,Cells, Cultured - Abstract
Mesangial changes in a variety of pathologic conditions involve mesangial cell proliferation and mesangial matrix remodelling. Heparin has been shown to prevent these processes in vivo. In vitro, heparin interferes with cell growth, proto-oncogene expression, synthesis of specific proteins, and extracellular matrix composition. In some cell types, it seems to interact with intracellular protein kinase C-dependent pathways. The effect of heparin on the mesangial plasminogen activating system (tissue type plasminogen activator, t-PA, and plasminogen activator inhibitor type 1, PAI-1), which is thought to be involved in matrix remodelling, has not been previously reported.Cultured human mesangial cells were stimulated by 10% fetal calf serum (FCS) or 16 nM phorbol myristate acetate (PMA) in the presence or absence of anticoagulant or nonanticoagulant heparins. Cell proliferation, synthesis of t-PA and PAI-1, cell morphology, and PAI-1 matrix deposition were studied using cell counting, [3H]thymidine incorporation, specific t-PA and PAI-1 enzyme-linked immunosorbent assay, Northern blot analysis, light microscopy, immunofluorescence and immunogold silver staining with combined bright-field and epipolarization microscopy.Heparin partially inhibited FCS-stimulated cell growth but not PMA-induced thymidine incorporation. FCS and PMA stimulated t-PA (p0.05 and p0.01, respectively) and PAI-1 synthesis (p0.05 and p0.01 respectively). Heparin selectively and partially inhibited FCS-stimulated t-PA, but not PAI-1 synthesis. It has no effect on PMA-stimulated t-PA or PAI-1 synthesis but prevented cell shape-changes induced by PMA, suggesting that heparin inhibits some but not all protein kinase C (PKC)-dependent effects and that heparin block in t-PA synthesis is distal to PKC activation. Heparin decreased PAI-1 matrix accumulation. Similar distal to PKC activation. Heparin decreased PAI-1 matrix accumulation. Similar results were observed with anticoagulant and nonanticoagulant heparin fragments.In human mesangial cells, anticoagulant and nonanticoagulant heparin exert an antiproliferative effect and may prevent mesangial matrix changes by decreasing FCS-stimulated t-PA synthesis and PAI-1 deposition in the matrix. Heparin is able to inhibit PKC-dependent cell shape changes but not PKC-dependent t-PA or PAI-1 synthesis. It also inhibits PKC-independent cell proliferation and t-PA synthesis. These results suggest multiple intracellular sites of action for heparin, unrelated or distal to PKC activation.
- Published
- 1994
23. Induction of MHC class II molecules HLA-DR, -DP and -DQ and ICAM 1 in human podocytes by gamma-interferon
- Author
-
C, Baudeau, F, Delarue, C J, Hé, G, Nguyen, C, Adida, M N, Peraldi, J D, Sraer, and E, Rondeau
- Subjects
HLA-DP Antigens ,Kidney Glomerulus ,Fluorescent Antibody Technique ,Epithelial Cells ,HLA-DR Antigens ,Blotting, Northern ,Flow Cytometry ,Intercellular Adhesion Molecule-1 ,Epithelium ,Interferon-gamma ,Gene Expression Regulation ,HLA-DQ Antigens ,Humans ,RNA, Messenger ,Cells, Cultured ,Receptors, Interferon - Abstract
MHC class II-encoded molecules HLA-DR, -DP and -DQ play a pivotal role in the human immune response. Their constitutive expression is restricted to a number of immunocompetent cells referred to as antigen-presenting cells. However, gamma-interferon (gamma-IFN) has been shown to induce MHC class II molecule expression in several epithelia. Using flow cytometric analysis, we show here that normal and SV40-transformed human podocytes in culture constitutively expressed gamma-IFN receptors. We also show that MHC class I molecules are constitutively expressed in these cells and that HLA-DR, -DP and -DQ expression, which is not found in unstimulated cells, can be induced by gamma-IFN stimulation. This induction was a time-dependent event, a lag phase of 24-48 h being necessary for MHC class II molecules to become detectable at the cell surface by flow cytometric analysis. Induction of MHC class II molecules in human podocytes also showed a concentration dependence, a plateau being reached at a concentration of 500 IU of gamma-IFN/ml of culture medium. This effect was blunted by coincubation of the cells with an antihuman gamma-IFN receptor monoclonal antibody. HLA-DR expression was associated with specific mRNA accumulation, as detected by Northern blot analysis. By indirect immunofluorescence, the intercellular adhesion molecule 1 was also induced by gamma-IFN stimulation. Induction of DR, DP and DQ in human podocytes may be involved in the pathogenesis of immune glomerulonephritis in man.
- Published
- 1994
24. Goodpasture's syndrome with asymptomatic renal involvement. Disappearance of antiglomerular basement membrane antibodies deposits after treatment
- Author
-
L, Lamriben, O, Kourilsky, B, Mougenot, P, Ronco, and J D, Sraer
- Subjects
Adult ,Male ,Plasma Exchange ,Anti-Glomerular Basement Membrane Disease ,Biopsy ,Immunoglobulin G ,Kidney Glomerulus ,Humans ,Kidney ,Basement Membrane - Published
- 1993
25. [Reduction of TNF-alpha release and clinical effects of the first injection of OKT3]
- Author
-
Q, Meulders, T, Dallel, M N, Peraldi, A, Kanfer, J D, Sraer, and E, Rondeau
- Subjects
Graft Rejection ,Tumor Necrosis Factor-alpha ,T-Lymphocytes ,Humans ,Drug Therapy, Combination ,Prospective Studies ,Kidney Transplantation ,Lymphocyte Depletion ,Antilymphocyte Serum ,Muromonab-CD3 - Abstract
In order to prevent the adverse effects of a first OKT3 injection in renal transplant recipients, we administered polyclonal antilymphocyte globulins (ATG Fresenius, 4 mg/kg/j) for 3 days before OKT3 injection. Compared with a historical group of 5 patients who did not receive ATG pretreatment before OKT3 injection, the patients who were pretreated by ATG had a significantly lower absolute number of circulating lymphocytes before the first OKT3 injection (363 +/- 107 vs 1,230 +/- 80/mm3, P0.001), a lower raise in plasma TNF-alpha level 2 hours after OKT3 injection (178 +/- 42 vs 735 +/- 127 pg/ml, P0.005) and a significant decrease in frequency and intensity of clinical symptoms, mainly chills, dyspnea, and headaches. However, fever and peak creatinine level were similar in both groups. A 80 percent success rate of crisis treatment was achieved in both groups and there was no increase in infectious complications. In conclusion, pretreatment with ATG induces a lymphocyte depletion, and decreases the amounts of TNF-alpha released as well as the side-effects of a first OKT3 injection.
- Published
- 1992
26. Plasminogen activator inhibitor-1 deposition in the extracellular matrix of cultured human mesangial cells
- Author
-
J, Hagège, M N, Peraldi, E, Rondeau, C, Adida, F, Delarue, R, Medcalf, W D, Schleuning, and J D, Sraer
- Subjects
Extracellular Matrix Proteins ,Time Factors ,Nucleic Acid Hybridization ,Immunohistochemistry ,Urokinase-Type Plasminogen Activator ,Extracellular Matrix ,Glomerular Mesangium ,Plasminogen Inactivators ,Tissue Plasminogen Activator ,Endopeptidases ,Microscopy, Electron, Scanning ,Humans ,RNA, Messenger ,Cycloheximide ,Cells, Cultured ,Electron Probe Microanalysis ,Research Article - Abstract
Human mesangial cells secrete tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), the latter being secreted in large excess in vitro. We demonstrate that PAI-1 is a major component of the extracellular matrix of cultured human mesangial cells, where its deposition is dependent on cell density. By immunogold silver staining, epipolarization microscopy and dispersive X-ray spectrometry, we have shown that matrix-associated PAI-1 is synthesized by spreading human mesangial cells, as indicated by the time-dependent accumulation of PAI-1 and the inhibitory effect of cycloheximide. Furthermore, by in situ hybridization, PAI-1 mRNA was detected in cultured mesangial cells. t-PA is present inside the cells, or at the cell surface, but is never associated with the extracellular matrix. Exogenous t-PA can remove matrix-associated PAI-1 without affecting cell adhesion. A similar effect was obtained by addition of urokinase-type plasminogen activator (u-PA) but not with fibrinolysis unrelated enzymes. In conclusion, PAI-1 is synthesized by human cultured mesangial cells and is deposited in the extracellular matrix by nonconfluent cells, whereas less PAI-1 is seen between confluent cells. This can explain the absence of detectable PAI-1 in normal human kidney biopsies. t-PA released by mesangial cells can bind and detach matrix PAI-1.
- Published
- 1992
27. [Extracapillary glomerulonephritis with fibrin deposits. Role of thrombin]
- Author
-
J D, Sraer
- Subjects
Glomerulonephritis ,Thrombin ,Animals ,Humans ,Cells, Cultured - Abstract
Fibrin deposits are frequent in experimental and human glomerulonephritides. In rapidly progressive glomerulonephritis (RPGN), fibrin deposits are considered as a factor generating glomerular sclerosis leading to renal failure. In RPGN, proliferation of epithelial cells associated with macrophages and fibrin deposits is observed in Bowman's space. It is known that 1) thrombin may be locally generated by tissue factor from glomerular cells and macrophages, 2) active thrombin may be adsorbed into the plug. Using immortalized human glomerular epithelial cells, we have tested the hypothesis that active thrombin may be a potential mediator of cellular proliferation, fibrin deposits persistency and collagen IV synthesis. The results clearly demonstrate that epithelial cells bind specifically iodinated alpha-thrombin. Thereafter, these cells synthesize specific inhibitors of plasminogen activators, converting their fibrinolytic activity into antifibrinolytic activity. Moreover, they synthesize soluble form of type IV collagen. A new therapeutical approach of RPGN may be taken into account based on the ability of new drugs inhibiting the binding of thrombin on its specific receptors, and/or inhibiting the extrinsic pathway of the fibrin formation.
- Published
- 1992
28. [Role of hemostasis in the formation of crescents in extracapillary glomerulonephritis]
- Author
-
E, Rondeau, G, Nguyen, C, Adida, M N, Peraldi, A, Kanfer, and J D, Sraer
- Subjects
Fibrin ,Hemostasis ,Glomerulonephritis ,Kidney Glomerulus ,Thrombin ,Animals ,Humans - Abstract
Extracapillary glomerulonephritis are associated with fibrin deposition in the urinary space of the glomerulus. Such deposits were correlated with the severity of the disease and with a poor renal outcome. Fibrin formation involves an activation of the coagulation cascade either through the intrinsic pathway, Hageman factor being activated by the altered glomerular basement membrane, either by the extrinsic pathway, infiltrating monocytes and glomerular cells exhibiting a procoagulant activity i.e. thromboplastin or tissue factor. Treatments with heparin or warfarin were shown to decrease the severity of experimental glomerular diseases. A similar beneficial effect was obtained with a monocyte-depleting serum and more recently with a treatment by a tissue type plasminogen activator. Glomerular cells also produce a fibrinolytic activity which could be too low or uneffective on extracapillary fibrin deposits if they contain high amounts of plasminogen activator inhibitors. Thrombin has procoagulant activity, antifibrinolytic activity and has cellular chemotactic and proliferative effects. It could play a major role in the pathogenesis of crescent formation.
- Published
- 1992
29. [Treatment of cytomegalovirus infections with ganciclovir in kidney transplant recipients. Clinical and pharmacokinetic study]
- Author
-
E, Rondeau, C, Farquet, D, Fries, and J D, Sraer
- Subjects
Adult ,Male ,Cytomegalovirus Infections ,Drug Evaluation ,Humans ,Female ,Middle Aged ,Infusions, Intravenous ,Ganciclovir ,Kidney Transplantation - Abstract
Ganciclovir (DHPG) was used in 32 renal transplant recipients with proven cytomegalovirus (CMV) disease. Mean time of CMV occurrence from grafting was 49 days. CMV disease was recognized on the combination of both clinical signs and histological or virological findings. DHPG treatment, adapted to renal function was given for 14 days and a pharmacokinetic study was performed at days 1, 7 and 14. Twenty nine patients, 10 of whom has severe to moderate disease, were improved by treatment. Three patients died, 2 of them with severe pulmonary and hepatic diseases. Few adverse effects were observed (leucopenia: n = 7, thrombopenia: n = 2, abdominal pain: n = 1). CMV was no longer found in virological samples in 80 percent of the patients. Maximal plasma concentration of DHPG (9.3 +/- 0.3 micrograms/ml, m +/- SEM) was reached at the end of the one hour infusion and decreased according to a biexponential model. The half life of elimination was 3.35 +/- 0.32 hours, the metabolic clearance 128 +/- 7 ml/min and the distribution volume about 50 percent body weight (0.48 +/- 0.02 l/kg). The clearance of DHPG was greater than creatinine clearance, and was linearly correlated with it, suggesting that renal elimination was important, both by glomerular filtration and tubular secretion. These results indicate that DHPG is effective and well tolerated for the treatment of CMV disease in renal transplant recipients. Renal elimination of the drug requires dosage adjustment to renal function.
- Published
- 1991
30. [TNF-alpha synthesis by circulating mononuclear cells in patients undergoing kidney transplantation]
- Author
-
Q, Meulders, E, Rondeau, F, Delarue, R, Lacave, and J D, Sraer
- Subjects
Adult ,Graft Rejection ,Male ,Blood Cells ,Reference Values ,Tumor Necrosis Factor-alpha ,Humans ,Interleukin-2 ,Female ,Immunoradiometric Assay ,Postoperative Period ,Middle Aged ,Kidney Transplantation - Abstract
In 7 patients who received renal transplant, systematic blood samples and cytoaspiration of the graft were performed every 3 days after grafting. In vitro TNF-alpha generation by circulating mononuclear cells and by cells infiltrating the graft were measured under basal conditions and after stimulation by recombinant IL-2 (50 U/ml). TNF-alpha concentration was determined by immunoradiometric assay (IRMA). Not enough cells could be collected by cytoaspiration to measure TNF-alpha concentration. In contrast, the generation of TNF-alpha by circulating mononuclear cells was detectable. It increased 24 to 48 hours before the rejection crisis and decreased after successful treatment and return of creatinin level to initial value. IL-2 increased TNF-alpha production and was more effective under normal conditions (10 to 15 fold increase) than during rejection episodes (1.3 to 2.4 fold). These results suggest that TNF-alpha is produced by mononuclear cells during rejection episodes and could be used as a marker of rejection. Further studies are required to determine its sensitivity and specificity.
- Published
- 1991
31. [TNF-alpha synthesis by cells from bronchioloalveolar lavage and by circulating mononuclear cells in recipients of heart-lung transplantation]
- Author
-
E, Rondeau, J, Cerrina, F, Delarue, F L, Ladurie, P, Hervé, A, Chapelier, P, Dartevelle, and J D, Sraer
- Subjects
Adult ,Graft Rejection ,Male ,Blood Cells ,Heart-Lung Transplantation ,Tumor Necrosis Factor-alpha ,Humans ,Interleukin-2 ,Female ,Immunoradiometric Assay ,Postoperative Period ,Middle Aged ,Bronchoalveolar Lavage Fluid - Abstract
In 10 patients who received a heart lung transplant, TNF-alpha generation by cells collected during bronchioloalveolar lavages (n = 30) and by circulating mononuclear cells was measured. Basal and recombinant IL-2-stimulated productions (50 U/ml) were measured. TNF-alpha concentration was determined by an immunoradiometric assay (IRMA). Circulating mononuclear cells produced at least 4 times less TNF-alpha than BAL cells. Rejection episodes or CMV diseases were not associated with significant changes in TNF-alpha generation. Recombinant IL-2 increased this production in both cell populations but the magnitude of this effect was smaller in BAL cells, suggesting an in vivo preactivation.
- Published
- 1991
32. [Treatment of cytomegalovirus infections in renal transplants]
- Author
-
E, Rondeau, M N, Peraldi, A, Kanfer, and J D, Sraer
- Subjects
Cytomegalovirus Infections ,Immunization, Passive ,Acyclovir ,Cytomegalovirus ,Humans ,Viral Vaccines ,Ganciclovir ,Kidney Transplantation - Abstract
Primary cytomegalovirus (CMV) disease can be prevented in renal transplant recipient with the use of either CMV hyperimmune globulin or acyclovir. When started before transplantation and continued for 12 to 16 weeks, these treatments decrease significantly the incidence of primary CMV disease. However they are not always effective and their effectiveness for the prevention of CMV reinfection or reactivation has not been established. Other prophylactic methods, such as vaccination or interferon alpha are not effective. Ganciclovir has been shown to be effective for the treatment of overt CMV disease, provided it is administered early. Combined treatments with CMV hyperimmune globulins and ganciclovir can be used in the most severe forms of the disease. Foscarnet can also be effective, however its nephrotoxicity limits its use in renal transplant recipients.
- Published
- 1991
33. Efficacy of early treatment of cytomegalovirus infection by ganciclovir in renal transplant recipients
- Author
-
E, Rondeau, C, Farquet, P, Ruedin, D, Fries, and J D, Sraer
- Subjects
Adult ,Immunosuppression Therapy ,Male ,Clinical Trials as Topic ,Cytomegalovirus Infections ,Humans ,Female ,Ganciclovir ,Kidney Transplantation - Published
- 1990
34. Tumor necrosis factor alpha (TNF-alpha) production by cells of bronchioloalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) in cardiopulmonary transplant recipients
- Author
-
E, Rondeau, J, Cerrina, F, Delarue, F L, Ladurie, P, Herve, A, Chapelier, P, Dartevelle, and J D, Sraer
- Subjects
Graft Rejection ,Immunosuppression Therapy ,Male ,Heart-Lung Transplantation ,Tumor Necrosis Factor-alpha ,Leukocytes, Mononuclear ,Humans ,Female ,Middle Aged ,Therapeutic Irrigation ,Lung ,Cells, Cultured - Published
- 1990
35. Interleukin-2 stimulation of tumor necrosis factor synthesis by peripheral blood mononuclear cells in renal allograft rejection
- Author
-
Q, Meulders, E, Rondeau, F, Delarue, R, Lacave, and J D, Sraer
- Subjects
Graft Rejection ,Immunosuppression Therapy ,Male ,Tumor Necrosis Factor-alpha ,Biopsy, Needle ,In Vitro Techniques ,Kidney Transplantation ,Reference Values ,Leukocytes, Mononuclear ,Humans ,Interleukin-2 ,Transplantation, Homologous ,Female ,Postoperative Period - Published
- 1990
36. Fibrin deposition and adaptive changes in glomerular procoagulant and fibrinolytic activities in rat renoprival nephropathy
- Author
-
P, Ruedin, B, Mougenot, D, Ruedin, E, Rondeau, J D, Sraer, R, Lacave, and A, Kanfer
- Subjects
Male ,Fibrin ,urogenital system ,Fibrinolysis ,Kidney Glomerulus ,Rats, Inbred Strains ,urologic and male genital diseases ,Adaptation, Physiological ,Rats ,Animals ,Methacrylates ,Kidney Diseases ,Thromboxane-A Synthase ,Blood Coagulation ,Research Article - Abstract
To investigate the mechanisms which may influence fibrin deposition in the remnant kidney, glomerular morphology and the haemostatic properties of isolated glomeruli were assessed in two groups of rats, 30 days after surgical removal of three-quarters of the total renal parenchyma, and compared to glomeruli in sham-operated controls. One group was given the thromboxane synthetase inhibitor OKY 046 and the other was not. Fibrin deposition occurred in about 20% of glomeruli, of which 4% exhibited segmental necrotizing lesions. Concomitantly, glomerular procoagulant activity dropped to 40% of the control level and glomerular fibrinolytic activity rose to 120-130% of this level. Inhibition of thromboxane synthesis did not affect fibrin deposition, glomerular haemostasis or the development of renal insufficiency. In an additional group of unilaterally nephrectomized rats, procoagulant activity also markedly decreased in the remaining kidney. These results indicate that in the rat remnant kidney, alterations in glomerular haemostatic properties tend to have antithrombotic effects which seem to constitute an adaptive reaction by an autacoid system to glomerular fibrin deposition.
- Published
- 1990
37. Plasminogen activator inhibitor 1 in renal fibrin deposits of human nephropathies
- Author
-
E, Rondeau, B, Mougenot, R, Lacave, M N, Peraldi, E K, Kruithof, and J D, Sraer
- Subjects
Male ,Fibrin ,Plasminogen Inactivators ,Tissue Plasminogen Activator ,Fluorescent Antibody Technique ,Humans ,Female ,Kidney Diseases ,Kidney ,Urokinase-Type Plasminogen Activator - Abstract
The persistency of fibrin deposits in the kidney during renal diseases could reflect either a defective release of plasminogen activators (PA) or a local excess of PAI. In order to investigate this question, we studied human renal biopsies by immunofluorescence technique with specific antibodies for fibrin, tissue-type plasminogen activator (t-PA), urokinase (u-PA), PAI-1 and PAI-2. By this technique t-PA could be detected in the glomerular flocculus and the endothelium of small arteries of the normal control kidneys. We failed to detect significant fluorescence with other antibodies in normal kidneys. Conversely, in cases of vascular nephropathy with thrombosis the positive fluorescence obtained with anti-fibrin antibodies at the site of thrombosis was associated with a positive fluorescence with anti-PAI-1 and to a lesser extent with anti-t-PA antibodies. u-PA and PAI-2 were not detected in these lesions. Similarly in the most severe forms of crescentic glomerulonephritis, extracapillary fibrin deposits were associated with PAI-1. In one case u-PA was also detected. This is in agreement with our previous findings that glomerular epithelial cells release both PAI-1 and the inactive form of u-PA (pro u-PA). Thus, our results support the hypothesis that PAI-1, which is able to inhibit both t-PA and u-PA, may play a major role in the persistency of fibrin deposits in the human kidneys during pathological conditions.
- Published
- 1990
38. Retroperitoneal Laparoscopic Nephrectomy of Native Kidneys in Renal Transplant Recipients
- Author
-
J. D. Doublet, M. N. Peraldi, H. Monsaint, M. Tligui, J. D. Sraer, B. Gattegno, and P. Thibault
- Subjects
Urology - Published
- 1998
39. Evidence for glomerular receptors for parathyroid hormone
- Author
-
R. D. Hesch, J. D. Sraer, Raymond Ardaillou, Dominique Chansel, Josée Sraer, and H. Jueppner
- Subjects
medicine.medical_specialty ,biology ,Physiology ,Parathyroid hormone receptor ,Chemistry ,Antigen-antibody reactions ,Kidney Glomerulus ,Parathyroid hormone ,Receptors, Cell Surface ,Adenylyl Cyclases ,Antibodies ,Antigen-Antibody Reactions ,Endocrinology ,Antibody Specificity ,Parathyroid Hormone ,Internal medicine ,medicine ,biology.protein ,Calcium-sensing receptor ,Antibody ,Receptor - Published
- 1978
40. Production of 5-lipoxygenase pathway metabolites by peripheral leucocytes in capillary leak syndrome (Clarkson disease)
- Author
-
Josée Sraer, R. Lacave, J. D. Sraer, L. Moulonguet Doleris, Marcelle Bens, and E. Rondeau
- Subjects
Adult ,Male ,medicine.medical_specialty ,Clinical Biochemistry ,Radioimmunoassay ,Vascular permeability ,Endogeny ,Arachidonate Lipoxygenases ,Leukotriene B4 ,Biochemistry ,Asymptomatic ,Capillary Permeability ,chemistry.chemical_compound ,Internal medicine ,Hydroxyeicosatetraenoic Acids ,Leukocytes ,medicine ,Humans ,Systemic capillary leak syndrome ,Calcimycin ,Chromatography, High Pressure Liquid ,Arachidonate 5-Lipoxygenase ,biology ,General Medicine ,medicine.disease ,In vitro ,Endocrinology ,chemistry ,Arachidonate 5-lipoxygenase ,Immunology ,biology.protein ,Female ,SRS-A ,Arachidonic acid ,Hypotension ,medicine.symptom ,Capillary Leak Syndrome - Abstract
Periodic systemic capillary leak syndrome (Clarkson disease) is characterized by unexplained attacks of a marked increase in capillary permeability. As leukotrienes, derived from arachidonic acid via the 5-lipoxygenase pathway, enhance capillary permeability, we studied arachidonate metabolism in leucocytes of a patient with capillary leak syndrome. Leucocyte-platelet suspensions, prepared from blood collected from the patient during asymptomatic periods (n = 11) produced greater amounts of 5-hydroxyeicosatetraenoic acid (5-HETE) than control suspensions (P less than 0.05). Peripheral leucocytes, collected during attacks (n = 3) and studied without addition of A23187 released LTB4 in vitro but not sulphidopeptides leukotrienes. This result was never observed with leucocytes from control subjects or from the patient out of a crisis. These results suggest that in the patient, peripheral leucocytes could be stimulated by an unknown, as yet to be determined, endogenous factor to produce more 5-HETE and LTB4. Whether LTB4 plays a pathogenic role in the capillary leakage remains to be determined.
- Published
- 1987
41. Role Des Cellules Dans La Regulation De L'equilibre Acido-Basique*
- Author
-
R. Ardaillou, J.-D. Sraer, and M. Paillard
- Subjects
Membrane potential ,business.industry ,Intracellular pH ,Chronic acidosis ,General Medicine ,Equivalent ,Linear relationship ,Yield (chemistry) ,Extracellular ,Biophysics ,Medicine ,medicine.symptom ,business ,Acidosis - Abstract
SummaryCells take part in acid-base equilibrium regulation. At most 15 mEq H+ ions per kg are neutralized during acute acidosis in man or in dog; 50 % of this load are neutralized by cellular buffers. The amount of buffers set in during chronic acidosis is far more important. It is essentially supplied by the skeleton. Intracellular pH (pH1) measurement in mammals may be accomplished by two types of techniques : indirect, based on the distribution of a weak acid or base, or direct, using glass microelectrodes. Indirect methods, using HCO3-/CO2 system or dimethyl-oxazolidinedione (DMO), yield pH1 values (muscular cells) close to 7 for extracellular pH (PHE) of 7.40. They also demonstrate the lack of linear relationship between pH1 and pHE, suggesting on autonomous regulation of pH1, linked with cellular metabolism. Direct methods yield pH1 values (muscular cells) close to 6 for pHE of 7.40/, and membrane potential of —90 mV. They demonstrate a simple linear relationship between pH1 and pHE, which suggests ...
- Published
- 1970
42. Acute Renal Failure
- Author
-
A. Kanfer, O. Kourilsky, J. D. Sraer, and G. Richet
- Published
- 1983
43. [Plasma exchange by membrane filtration. Experience of the Tenon Hospital]
- Author
-
O, Kourilsky, J D, Sraer, J, Martinez-Ara, H, Tembely, P, Verroust, P, Ronco, D, Brault, A M, Rouquette, R, Egler, C, Poyau-Lemaux, I, Gerotta, and G, Richet
- Subjects
Plasma Exchange ,Collagen Diseases ,Costs and Cost Analysis ,Humans ,Membranes, Artificial ,Plasmapheresis ,Acute Kidney Injury ,Kidney Transplantation - Published
- 1981
44. Glomerular hemostasis in normal and pathologic conditions
- Author
-
J D, Sraer, A, Kanfer, E, Rondeau, and R, Lacave
- Subjects
Fibrin ,Hemostasis ,Fibrinolysis ,Kidney Glomerulus ,Animals ,Humans ,Kidney Diseases ,Thrombosis ,Blood Coagulation - Published
- 1988
45. [Kidney puncture biopsy in acute renal failure]
- Author
-
G, Richet, J D, Sraer, O, Kourilsky, and L, Morel-Maroger
- Subjects
Biopsy, Needle ,Humans ,Acute Kidney Injury ,Kidney ,Uremia - Published
- 1978
46. [A case report of kidney transplantation]
- Author
-
J D, Sraer and O, Kourilsky
- Subjects
Adult ,Male ,Postoperative Complications ,Perioperative Nursing ,Humans ,Kidney Failure, Chronic ,Kidney Transplantation - Published
- 1982
47. Physiological significance of increased levels of endogenous atrial natriuretic factor in human acute renal failure
- Author
-
A, Kanfer, J C, Dussaule, S, Czekalski, E, Rondeau, J D, Sraer, and R, Ardaillou
- Subjects
Adult ,Aged, 80 and over ,Male ,Blood Volume ,Sodium ,Humans ,Female ,Acute Kidney Injury ,Middle Aged ,Prognosis ,Cyclic GMP ,Atrial Natriuretic Factor ,Aged - Abstract
In twelve patients with acute renal failure, mean plasma levels of atrial natriuretic factor (ANF) and of its second messenger cGMP were found elevated at the early phase of the disease, but tended to return towards normal values at recovery. Variations of plasma ANF and cGMP were correlated significantly (p less than 0.05) with those of total blood volume. At the early phase of the disease, plasma ANF was also correlated with the excreted fraction of filtered sodium (FENa) (r = 0.95). Moreover, plasma ANF and FENa peaked concomitantly at the onset of the diuretic phase in the five patients who were not treated by diuretics or dialysis and were studied sequentially during the course of the disease. It is suggested that enhanced plasma ANF levels might reflect one of the mechanisms of adaptation controlling body fluid balance in acute renal failure.
- Published
- 1989
48. [Severe internal hemorrhages due to spontaneous intestinal rupture in hemodialysis patients]
- Author
-
A, Meyrier, C, Verger, K S, Ang, J D, Sraer, O, Kourilsky, and J, Roland
- Subjects
Adult ,Male ,Rupture, Spontaneous ,Renal Dialysis ,Humans ,Female ,Middle Aged ,Gastrointestinal Hemorrhage - Published
- 1979
49. [Prostaglandin synthesis by dispersed cells from the submandibular gland of the rat. Effect of pH and calcium]
- Author
-
J R, Nejar, I, Sedillot-Occhiminuti, F, Delarue, and J D, Sraer
- Subjects
Male ,Prostaglandins E ,Indomethacin ,Prostaglandins F ,Submandibular Gland ,Rats, Inbred Strains ,Hydrogen-Ion Concentration ,Dinoprost ,Dinoprostone ,Rats ,Prostaglandins ,Animals ,Calcium ,Chromatography, High Pressure Liquid - Abstract
Qualitative study by HPLC of PGs synthesis by rat sub-maxillary glands cells shows that PGE2 and PGF2 alpha are synthetized predominantly. PGF2 alpha synthesis is essentially related to extracellular ionic concentration of H+ and Ca++ suggesting that the activation of phospholipase A2 or C is more important than the concentration of other enzymes such as 9 intracytoplasmic ceto reductase. Modulation of PGs synthesis by sub-maxillary gland cells by extra cellular factors suggests a possible interaction between hormones (angiotensine II, catecholamines) and phospholipase A2 or C of the cell membrane of these cells.
- Published
- 1985
50. [Adenylate cyclase and guanylate cyclase activity in the isolated kidney glomerulus of the rat]
- Author
-
J D, Sraer, M, Wolff, F, Delarue, and J, Sraer
- Subjects
Enzyme Activation ,Guanylate Cyclase ,Kidney Glomerulus ,Animals ,In Vitro Techniques ,Autonomic Agents ,Hormones ,Adenylyl Cyclases ,Rats - Abstract
Isolated rat renal glomeruli contain an adenylate cyclase system and guanylate cyclase system. Adenylate cyclase was strikingly activated by purified parathyroid hormone, epinephrine, prostaglandin I2 and histamine. The demonstration of PTH activated adenylate cyclase in glomeruli raises the possibility of a role of this hormone in regulation of glomerular filtration rate. Guanylate cyclase was strikingly activated by CA2+, nitrate derivatives such as sodium nitroprusside. Its role remained still unknown.
- Published
- 1979
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.