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Biomedical subjects

D Droz

Publications and source records attributed to D Droz.

At least 55 records · Page 3Linked to original sources

[Value of postoperative radiotherapy in malignant tumors of the upper urinary tract. Apropos of a series of 26 patients].

To evaluate the role of adjuvant radiation therapy in invasive transitional cell carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26 patients who underwent radical surgery plus post-operative prophylactic irradiation for such a tumor. Between 1980 and October 1993, 18 men and eight women (mean age: 65 +/- 9 years) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage C in 15 patients (58%). Tumor grade was 2 in ten patients, 3 in 15 and unknown in one. Nine patients had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy to the tumor bed (23 patients) and/or regional nodes (18 patients). After a mean follow-up of 45 months, 13 patients (50%) were alive and 11 were disease-free. Local tumor relapse, nodal recurrence, metastasis and second urothelial location were noted in one, four (15%), 14 (54%) and eight patients (30%) respectively. Overall 5-year survival and 5-year disease-free survival were 49% and 30% respectively. Overall 5-year survival rates were 60% for stage B and 19% for stage C disease (P = 0.07), 43% for node-negative versus 15% for node-positive cancer (P = 0.04) and 90% for grade 2 and 0% for grade 3 tumors (P < 0.01). In this study using a radio-surgical approach, local control of disease and survival were similar to those reported previously in surgical series. Prophylactic post-operative radiation therapy is not recommended.

Adult↗

[Value of cyclosporine in the treatment of the recurrence of nephrosis after renal transplantation].

From May 1992 to December 1994, 14 children with end stage renal failure secondary to steroid-resistant idiopathic nephrotic syndrome received a cadaver kidney graft. Immediate recurrence of the nephrotic syndrome occurred in four patients. In the four patients, a complete remission was observed shortly after the start of intravenous cyclosporin; two children received in addition methylprednisolone pulses for secondary rejection. Two children were still protein-free 9 and 15 months after transplantation. In the third patient, proteinuria relapsed after 9 months of complete remission and persisted in spite of the reintroduction of intravenous cyclosporin. The fourth graft was lost at 3.5 month from irreversible rejection. The creatinine clearance of the 3 functioning grafts was respectively: 73, 76 and 92 ml/mn/1.73 m2 16, 10 and 15 months after transplantation. Intravenous cyclosporin started shortly after the recurrence, maintaining blood levels between 200 and 300 ng/ml, may induce a remission in recurrent nephrotic syndrome after renal transplantation in childhood.

Child, Preschool↗

Expression of bcl-2 oncoprotein in renal cell tumours.

Expression of bcl-2 is associated with inhibition of apoptosis and extension of cell survival. The importance of apoptosis in relation to the development and progression of renal cell neoplasia remains undefined so far. In order to determine the expression of bcl-2 oncoprotein in normal and neoplastic renal cells, 37 renal tumours were investigated by immunolabelling, including 13 clear cell carcinomas, ten tubulopapillary carcinomas, four chromophobic renal cell carcinomas, and ten oncocytomas. Twenty-six samples of adjacent normal renal tissue served as controls. bcl-2 expression was correlated with cell proliferation activity as estimated by Ki67 antigen expression, and p53 protein expression in the tumour samples. The results demonstrate that in the normal kidney, positive bcl-2 immunostaining was present in glomerular parietal epithelial cells, in distal tubular cells, and in sparse proximal tubule cells. Renal cell tumours showed heterogeneous bcl-2 expression according to the tumour cell type. While the majority of carcinomas of clear cell type were usually negative or contained sparsely distributed positive cells, all tubulopapillary carcinomas were consistently positive for bcl-2. In oncocytomas and chromophobic carcinomas, there was a low percentage of bcl-2 immunoreactive tumour cells; some nuclear bcl-2 positivity was detected in one chromophobic tumour. These findings indicate variable bcl-2 oncoprotein expression in different types of renal cell tumours, with the highest level of expression in tubulopapillary carcinomas. No clear relationship was found between nuclear grade, cell proliferation activity, and level of bcl-2 expression. p53 protein was detected in only one tubulopapillary carcinoma.

Biomarkers, Tumor↗

Distribution of the extracellular matrix components in human glomerular lesions.

Most glomerular pathologies are associated with alterations of the matrix compartment. Using reagents directed against the alpha 1/alpha 2 and alpha 3 chains of type IV collagen [alpha 1/alpha 2(IV), alpha 3(IV)], laminin, heparan sulphate proteoglycan (HPG), fibronectin, collagen I, and collagen III, we investigated the modifications of the glomerular matrix components in several human glomerular lesions compared with normal kidney. In type I membranous glomerulonephritis (MGN) (nine cases), we did not observe alterations in the matrix component distribution. In MGN types II and III (five cases), the spikes and chainettes were made of the alpha 3(IV) chain, laminin, and HPG, while the alpha 1/alpha 2(IV) chains were localized along the subendothelial side of the glomerular basement membrane (GBM). In focal and segmental glomerulosclerosis (six cases), fibronectin, alpha 1/alpha 2(IV) chains, laminin, and small amounts of interstitial collagens were detected within the collapsed capillary loops; the newly formed matrix material between the podocytes and the GBM contained the alpha 1/alpha 2(IV) chains, laminin, and HPG but not the alpha 3(IV) chain. In crescentic glomerulonephritis (six cases), fibronectin was the most abundant and, in purely cellular crescents, the unique component. A basement membrane-like network containing laminin, HPG, alpha 1/alpha 2(IV) chains, and interstitial collagens developed in a second step between the crescent cells. Interstitial collagens were present in the crescent framework, even when the integrity of Bowman's capsule was preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinico-anatomical forms of primary glomerulonephritis].

The various clinicopathological forms of primary glomerulonephritis (GN) in humans include lipoid nephrosis with its histological variants (minimal change disease, focal segmental glomerular sclerosis, diffuse mesangial proliferation), membranous GN, IgA nephropathy, membranoproliferative GN (type I and type II) and crescentic GN. Each of these entities is characterised by pathological, clinical, and immunological features. Although the precise etiology of primary GN remains unknown, important progress from experimental models has been recently obtained in the understanding of the mechanisms of the glomerular lesions and their progression. Such investigations may afford possibility for preventing glomerular destruction.

Glomerulonephritis↗

Influence of various calcium intakes on calcium-oxalate crystalluria in rats on sodium-oxalate diet.

Forty adult male Wistar rats were placed in metabolic cages on a Ca-deficient diet (0.1%) for 7 days and then on a Ca-deficient, Na-oxalate (NaOx) enriched diet (20 mg/100 g) for another 14 days. The animals were subdivided into three groups receiving three different types of mineral water: group I (n = 13), Badoit (Ca 222 mg/l); group II (n = 14), Contrexéville (Ca 467 mg/l); and group III (n = 13), Evian (Ca 78 mg/l). Another series of 25 rats (group I, n = 9; group II, n = 8; group III, n = 8) underwent the same study protocol, except that they received a normal Ca diet (1%). On the low-Ca diet, urinary Ca-Ox monohydrate (COM) crystals were observed only under the Na-Ox diet, with a mean crystal number significantly greater in group III (16.7 +/- 4.5 crystals/mm3) than in group I or II rats (2.5 +/- 1.5 or 4.1 +/- 1.5 crystals/mm3, respectively). Urinary Ca concentrations decreased in all groups (P < 0.001) under the Na-Ox diet, while urinary oxalate concentrations increased in all groups (P < 0.001). On the normal Ca diet, COM crystal excretion was observed only with the Na-Ox-enriched diet, but in this case feeding the Na-Ox diet did not modify urinary oxalate excretion. Ca/Ox ratio was significantly lower under 0.1% Ca diet than under normal Ca diet, related with the type and the number of crystals observed, demonstrating that assessment of crystalluria can provide an index of disease severity. Moreover, the hardness of the drinking water influences urinary COM crystal excretion only under a low-Ca, oxalate-rich diet, suggesting that the total calcium intake rather than the water calcium content is an important factor in the occurrence of Ca-Ox nephrolithiasis.

Animals↗

Distribution of integrin subunits in normal human kidney.

We evaluated on serial sections the distribution of a large number of integrin alpha and beta chains in normal adult human kidney: 1) the beta 1 chain and its corresponding alpha subunits (alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, alpha 6), 2) alpha v and beta 3 chains, 3) the beta 2 chain and its corresponding alpha chains (alpha X, alpha M, alpha L), and 4) the beta 4 chain. We also evaluated ICAM-1, VCAM and ELAM and the major extracellular matrix components (ECM). A three step immunoperoxidase technique was used on frozen sections. Each cell of the kidney shows a specific distribution of these molecules. The relation with ECM and some of their ligands was evaluated. This immunohistochemical study shows that there is no strict colocalisation of a given ECM component with its specific receptor.

Adult↗

Composition of extracellular matrix and distribution of cell adhesion molecules in renal cell tumors.

BACKGROUND: Cell to cell and cell to matrix interactions play a major role in tumor growth and invasion. Therefore, we studied the composition of extracellular matrices and the distribution of cell adhesion molecules in 50 renal cell tumors of various types and various grades of malignancy as compared with nontumoral kidney. EXPERIMENTAL DESIGN: In the present study, we used immunolabeling with specific antibodies directed against the alpha 1, alpha 2, and alpha 3 chains of collagen type IV; laminin; heparan sulfate proteoglycan; fibronectin; collagen I; collagen III; the alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1, and beta 3 subunits of integrins; and ICAM-1, VCAM-1, and ELAM-1 molecules. RESULTS: In clear cell type carcinomas (24 cases) the basal laminae surrounding the tumor islets contained the alpha 1 and alpha 2 chains of collagen type IV and heparan sulfate proteoglycan in all cases, and laminin in 96% of the cases. The alpha 3 chain of collagen IV was present in only one case, whereas fibronectin, collagen I, and collagen III were detected in nearly 50% of the cases. The tumor cells expressed alpha 3, alpha 6, and beta 1 integrin subunits in all cases, alpha 5 in 25%, alpha v beta 3 in 54%, and alpha 2 in none. ICAM-1 was detected in all cases, and VCAM-1 in 58%. The expression of the alpha 6 subunit was weak in 2 tumors of high grade, whereas the alpha v subunit was expressed in 7 of 14 low grade and in 7 of 10 intermediate and high grade tumors. In tubulopapillary carcinomas with chromophilic cells (12 cases), the most prominent findings were the presence of the alpha 3 chain of collagen IV in tumor basal laminae in 66% and the expression of the alpha 2 integrin subunit by the tumor cells in 58% of the cases, both features characterizing distal renal tubules. In chromophobic carcinomas (4 cases), the tumor basement membranes were tenuous and contained no fibronectin or interstitial collagens. The tumor cells expressed the alpha 6, alpha 2, alpha 3, beta 1, and alpha nu beta 3 integrin subunits but neither ICAM-1 nor VCAM-1 molecules. In oncocytomas (10 cases), the tumor basement membranes contained the alpha 1, alpha 2, and alpha 3 chains of collagen IV, laminin, and heparan sulfate proteoglycan. Fibronectin was not detected, whereas interstitial collagens were present in half of the cases. In all tumors, cells expressed the alpha 6 and beta 1 integrin subunits, whereas alpha 2, alpha 3, and alpha nu beta 3 were present in 30%, 60%, and 90% of the cases, respectively. ICAM-1 and VCAM-1 were not detected. The vascular endothelial cells of the stroma expressed the alpha 1, alpha 5, alpha 6, and beta 1 integrin subunits in all 50 of the studied tumors. In addition, ICAM-1 was detected in 84%, VCAM-1 in 50%, and ELAM-1 in 34% irrespective of tumor cell type, growth, or nuclear grade. CONCLUSIONS: These results suggest that each type of renal cell tumor produces particular extracellular matrix components and expresses a characteristic repertoire of cell adhesion molecules, which could provide better understanding of the origin of these tumors. The expression of the alpha nu beta 3 integrin subunit was demonstrated in all types of renal cell tumors and was not found to be related to high grade tumors. Stromal vascular endothelial cells expressed activation molecules VCAM-1 and ELAM-1 in a significant number of cases in both benign and malignant tumors.

Adenocarcinoma, Clear Cell↗

International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology.

A group of renal pathologists, nephrologists, and transplant surgeons met in Banff, Canada on August 2-4, 1991 to develop a schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection. Development continued after the meeting and the schema was validated by the circulation of sets of slides for scoring by participant pathologists. In this schema intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+, to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other. The goal is to devise a schema in which a given biopsy grading would imply a prognosis for a therapeutic response or long-term function. While the clinical implications must be proven through further studies, the development of a standardized schema is a critical first step. This standardized classification should promote international uniformity in reporting of renal allograft pathology, facilitate the performance of multicenter trials of new therapies in renal transplantation, and ultimately lead to improvement in the management and care of renal transplant recipients.

Graft Rejection↗

Interleukin-6 and TNF alpha production in human renal cell carcinoma.

Several clinical and biological features suggest that cytokines implicated in the inflammatory response are produced by renal cell carcinoma (RCC). To define if alterations of tumor necrosis factor alpha (TNF alpha), interleukin 1 alpha (IL-1 alpha), IL-1 beta and IL-6 gene expression are present in this malignancy, samples from 19 tumors as well as samples from seven paired normal renal tissue were examined using Northern blot and immunohistochemical analysis. In addition, the expression of these cytokines was evaluated in seven RCC-derived cell cultures using Northern blot or RT-PCR. TNF alpha and IL-6 proteins were measured in culture supernatants using specific bio- and immunoassays. Consistent levels of IL-6 mRNA were detected in 17 of the 19 tested tumors whereas TNF alpha specific transcripts were present in seven of eight available RNA samples. TNF alpha and IL-6 mRNA were also detected in five of the seven paired normal kidneys. By immunolabeling, IL-6 antigen was not detected in RCC cells in any of the 19 studied samples. In contrast, using anti-TNF alpha antibody a strong labeling of stromal endothelia and macrophage cells was detected in all the 19 cases, and evident TNF alpha staining of the carcinoma cells themselves was observed in eight cases. Spontaneous IL-6 mRNA expression was detected in five RCC cell cultures and TNF alpha mRNA in four. The cultured cells exhibited positive TNF alpha immunolabeling in six of seven cases but were always IL-6 negative. Bioactive IL-6 was detected in all culture supernatants while bioactive TNF alpha was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Renal Cell↗

The detection of CR1 mRNA and CR1 antigen identifies the presence of immature podocytes in a case of Wilms' tumor (nephroblastoma).

Wilms' tumors (nephroblastomas) are heterogeneous tumors consisting of proliferating epithelial cells in glomeruloid bodies and tubule formations and of proliferating blastemal cells. Using a specific CR1 35S-labeled cDNA probe and CR1 antibodies, CR1 mRNA and CR1 antigen-expressing cells were detected in glomeruloid bodies in one case of Wilm's tumor. The concomitant expression of CR1 mRNA and CR1 antigen and the high level of CR1 mRNA expression that characterize podocytes at an early stage of glomerular maturation in the normal human fetal kidneys indicates that glomeruloid bodies are composed of immature podocytes.

DNA Probes↗