Loss of NOS1 expression in high-grade renal cell carcinoma associated with a shift of NO signalling.

In normal human kidney, NOS1 and soluble guanylate cyclase (sGC) are expressed in tubular epithelial cells, suggesting a physiological autocrine NO signalling pathway. Therefore, we investigated both NOS1 and sGC expressions in benign and malignant renal tumours. In addition, we examined the pattern of protein tyrosine nitration in normal and tumour tissue. NOS1 expression and activity were found to be downregulated, correlating with the tumour grade, as shown by immunohistochemistry, quantitative RT-PCR analysis, and histochemical detection of the NADPH-diaphorase activity of nitric oxide synthases (NOS). These results show that the autocrine NO signalling pathway is maintained in benign tumours and lost in malignant tumours. In contrast, sGC expression was maintained in renal tumours whatever the tumour type, a finding showing that tumour cells remain sensitive to the bioregulatory role of exogeneous NO(*). Finally, the staining pattern of protein tyrosine nitration, assessed by immunohistochemistry, parallelled that of NOS1 expression in normal renal parenchyma and benign tumours, supporting the concept that protein nitration was accounted for by NOS1 activity. In contrast, in malignant tumours, protein tyrosine nitration was accounted for by the production of reactive nitrogen oxide species by the inflammatory infiltrate. Altogether, these findings argue for a pattern of NO signalling similar in normal kidney and benign renal tumours, whereas it is completely different in malignant renal tumours.

[Testicular tumor in renal and pancreatic transplantation]. / Tumeur du testicule en transplantation rénale et pancréatique.

The authors report the case of a 49-year-old, insulin-dependent diabetic man treated by double kidney-pancreas transplantation. A T3, N3, M0 testicular tumour was discovered at the 8th month and treated by inguinal orchidectomy and 2 courses of chemotherapy. Immunosuppressant treatment was decreased without any consequences for the transplants. Seven years later, the patient was cured but still treated by haemodialysis for chronic rejection of the renal transplant. The pancreatic transplant was still functional and the patient is waiting for a second renal transplantation.

Comparative analysis of MiB1 and p53 expression in human bladder tumors and their correlation with cancer progression.

Expression of p53 and MiB1, markers of tumor proliferation, was evaluated in human bladder tumors, and correlated with ploidy and cancer progression in 83 consecutive patients. Transurethral resection of a newly diagnosed bladder tumor was performed in 73 cases, and systematic bladder biopsies were performed in 10 cases after bacillus Calmette-Guerin (BCG) treatment. p53 and MiB1 expression were performed by an immunohistochemical technique and the ploidy was determined on a frozen fragment of the tumor. p53 expression was correlated in relation to grade, stage and combination of grade and stage. MiB1 expression was correlated with cytological grade, and a significant difference was demonstrated between pT0 and pTa, pTa, and pT1, pTa and pT2 tumors but not between pT1 and > or = pT2 tumors. A discordance was observed for the comparison of p53 and MiB1 values, stage by stage, suggesting that these two techniques are independent of each other. A larger proportion of aneuploid tumors were positive for p53 and MiB1 (64.8 vs. 86.5%, respectively), but p53 and MiB1 immunostaining were not better indicators than ploidy alone to predict cancer progression.

Predominant Th1 cell infiltration in acute rejection episodes of human kidney grafts.

T-cells and their cytokines are thought to play a major role in the genesis of cellular infiltration and rejection in human kidney allografts. Production of Th1 (IFN-gamma) and Th2-type (IL-4 and IL-5) cytokines was assessed in a large series of T-cell clones, derived from core biopsies of kidney grafts in 10 patients with acute interstitial grade I/II rejection (AIR), 6 patients with a histology of "borderline rejection" (BLR) and 3 with cyclosporine A (CsA) toxicity, all receiving standard maintenance immunosuppression. Biopsies were pre-cultured in IL-2 in order to preferentially expand T-cells activated in vivo, and T-cell blasts were cloned with phytohemagglutinin (PHA) and IL-2 using a highly efficient (23 to 98%) cloning technique. A total of 483 T-cell clones obtained from AIR episodes were compared with 346 and 132 clones derived from patients with BLR episodes and CsA toxicity, respectively. In two series of 22 AIR and 77 BLR T-cell clones, alloreactivity against donor cells was shown by 25 and 14% of CD8+ and 21 and 4% of CD4+ clones, respectively. When stimulated by donor-derived EBV B-cells, all these alloreactive clones produced IFN-gamma, but not IL-4 or IL-5 (Th1 clones). Upon stimulation with PHA, the principal qualitative and quantitative differences between AIR- and BLR-derived T-cell clones were that cells derived from AIR patients: (i) showed significantly higher proportions (80 +/- 15 vs. 55 +/- 13%) of Th1 clones in their progeny; (ii) included smaller proportions (3 +/- 4 vs. 20 +/- 17%) of clones incapable of producing IFN-gamma, IL-4 or IL-5 ('null' clones); and (iii) produced significantly higher quantities of IFN-gamma (100 +/- 50 vs. 36 +/- 7 U/10(6) cells/ml), these quantities also being significantly correlated (r = 0.83) with the degree of interstitial graft infiltration (item 'i' in the Banff histological grading). The clones derived from CsA toxicity biopsies exhibited a pattern very similar to that found in BIR cases. These data lead us to conclude that the powerful inflammatory response elicited in acute rejection of a kidney graft recruits and activates both allospecific and non-specific Th1 effector cells, which are primed to high IFN-gamma production. Our results also suggest that IFN-gamma could contribute, at least in part, to the degree of graft infiltration and to the severity of the rejection episode.

Adenovirus-mediated gene transfer in rat liver of interleukin 4 but not interleukin 10 produces severe acute hepatitis.

Several immune responses are either limited to or concentrated in a given organ. Cytokines produced during ongoing immune responses have organ-localized effects that can be only partially mimicked upon their systemic delivery. Recombinant adenoviruses are efficient vectors to induce transient organ-localized cytokine expression. This allows in vivo analysis of the effects of cytokines produced spatially and temporally in a manner comparable to that observed during immune responses. The authors generated recombinant adenovirus for rat IL-4 (AdIL-4) and IL-10 (AdIL-10) to analyse the in vivo effects of these two important immunoregulatory molecules after gene transfer in the liver. It was first established that AdIL-4 and AdIL-10 were able to direct the production of biologically active cytokines by different rat cell types in vitro. Intraportal injection of doses of up to 10(10) pfu of AdIL-10 or control non-coding recombinant adenovirus were well tolerated, and hepatic histology showed only mild alterations. Conversely, animals receiving more than 2.5 x 10(9) pfu of AdIL-4 showed dose-dependent mortality, with clinical signs of hepatic dysfunction. Liver histology in animals receiving 2.5 x 10(9) pfu of AdIL-4 showed severe acute hepatitis with maximal lesions between day 7 and 14 and almost complete normalization by day 28 after gene transfer. The leukocyte infiltrate was composed primarily of mononuclear cells, but eosinophils and mast cells were significantly increased as compared to control animals. Hepatic function was also altered in animals that received AdIL-4, with kinetics similar to that of histological lesions. Our study describes a model for investigating cytokine function in vivo through liver-localized transgene expression mediated by adenoviral vectors and demonstrates that liver production of IL-4 but not IL-10 results in acute severe hepatitis.

[Outcome of nephrogenic metaplasia of the bladder in kidney transplant recipients]. / Devenir de la métaplasie néphrogène vésicale chez les transplantés rénaux.

OBJECTIVES: To evaluate the risk of recurrence and malignant degeneration of vesical nephrogenic metaplasia in renal transplant recipients. MATERIAL AND METHODS: Fourteen patients with known nephrogenic metaplasia were systematically followed. Vesical biopsies were performed with a resector, stained with eosin haemalun saffron, analysed and compared to initial results. Labelling by anti-EBV and anti-CMV monoclonal antibodies was performed in 5 cases of intense inflammatory reactions. RESULTS: All patients were males, with a median age of 39 years. Nephrogenic metaplasia had been diagnosed 7 to 80 months after renal transplantation (median = 37.8). Twelve patients were reviewed 5 to 116 months after the initial diagnosis (median = 52). Relapse was observed in 83% of cases, but without any malignant degeneration. CONCLUSION: Nephrogenic metaplasia is therefore a benign recurrent disease. The importance of the initial blood supply and fibrosis in the case of recurrence suggest a disorder of the blood supply, probably traumatic in origin. Only symptomatic patients are currently followed.

[Sarcomatoid variant of chromophobe renal cell carcinoma. Report of 2 cases]. / Variante sarcomatoïde du carcinome rénal à cellules chromophobes. A propos de 2 observations.

In this paper, we report two cases of sarcomatoid carcinoma arising in chromophobe carcinoma. The sarcomatoid component appeared as white, shiny areas, occupying less than 10% of each tumor and containing numerous mitotic figures. Whereas both components expressed cytokeratin, only the carcinomatous cells were positive for epithelial membrane antigen and only the sarcomatoid cells were found to express vimentine. Sarcomatoid transformation in chromophobe cell carcinoma has been reported exceptionally. An aggressive behavior may be expected. The variable proportion of sarcomatoid component may lead to multiplication of the samples, especially when white, firm and shiny areas are detected on gross findings.

[Vestigial cysts of the anterior intestine of unusual localization. Report of two cases]. / Kystes vestigiaux de l'intestin antérieur de localisation inhabituelle. A propos de deux observations.

Bronchogenic cysts and enteric cysts both result from an aberration of development of the anterior gut. Their usual location is the mediastinum. The abdominal or retroperitoneal location of such cysts is rare and raises problems in terminology and pathogenesis. We report two cases of an unusual location of bronchogenic and enteric cysts. We also recall the criteria of diagnosis and the pathogenesis.

[Wermer syndrome associated with a bilateral renal tumor]. / Syndrome de Wermer associé à une tumeur rénale bilatérale.

Wermer's syndrome is a polyendocrinopathy characterized by neoplasia of the parathyroidis, pancreas and the pituitary. We report a case, unique in our knowledge, of an unusual association of a bilateral renal tumors and Wermer's syndrome. The originality of this case is: Bilateral renal blow. Therapeutic difficulties. This manifestation may represent a new manifestation of this pleiotropic syndrome.

Late acute failure of well-HLA-matched renal allografts with capillary congestion and arteriolar thrombi.

Seventeen cases of a histologically and clinically unusual renal acute dysfunction in kidney recipients, individualized among a population of 1378, are reported. The basic histological lesion was a huge capillary congestion, associated with capillary and arteriolar thromboses or parenchymal necrosis in most patients, and contrasting with the absence of the classical features of acute cellular rejection, i.e., tubulitis, glomerulitis, edema, and infiltrate. The corresponding clinical history was characterized by its early timing in the course of transplantation (< 3 months), its sudden occurrence in patients usually having good transplant function, leading to end-stage renal failure in a few days, and its resolution under rejection treatment. The occurrence of this syndrome was significantly linked with a good HLA matching: 13 of the 17 recipients were HLA-DR matched (P < 0.0001). The etiology of this syndrome remains unknown. There was no evidence for graft vessel thrombosis. Because of some histological similarities, the usual causes of the hemolytic uremic syndrome, including bacterial and viral infections or cyclosporine arteriolopathy, were discussed. Acute vascular rejection was suspected, but the cross-match was negative on T lymphocytes in all cases and anti-HLA class I and II antibodies were not found to develop at the time of transplant dysfunction, except in 1 patient, in whom the detected anti-DR antibodies were not directed at the kidney donor. Anti-human umbilical vein endothelial cell antibodies, detected in an antibody-dependent cellular cytotoxicity assay, were present in 6 patients (of the 14 tested) at the onset of renal failure, but they were either absent (n = 3) or already present at the time of transplantation (n = 5) in the other 8 patients. Therefore, reliable arguments are lacking to conclude that this acute transplant dysfunction is an acute vascular rejection and its strong association with HLA matching has, as yet, no satisfactory explanation.

Captopril and aspirin in treatment of renal microangiopathy in primary antiphospholipid syndrome.

Treatment of antiphospholipid syndrome (APS) is controversial. We report a case of renal microangiopathy in a 40-year-old woman with APS. The nephropathy was isolated without signs of disseminated thrombotic microangiopathy or progressive systemic sclerosis. Similarities with sclerodermatous kidney and an increase in plasma renin activity led us to initiate treatment with aspirin and captopril, with excellent control of the renal syndrome. We believe this therapeutic regimen may be an effective means of treating the renal microangiopathy of APS.

[Metastasis from a cancer into another cancer. Apropos of a case]. / Métastase d'un cancer dans un autre cancer. A propos d'une observation.

Based on a case of metastatic basal cell carcinoma of lung to primary renal cell carcinoma, the authors review the literature from the first report by Campbell in 1968, and emphasize the very particular role of renal carcinoma as "preferential host" of metastases from another primary carcinoma. The specificity serum prealbumin of renal carcinoma is questionable and its contribution as a neuroendocrine marker is suggested.

Testicular tumor and the acquired immunodeficiency syndrome.

Immunocompromised patients, particularly those suffering from the acquired immunodeficiency syndrome (AIDS), present an increased risk of tumoral pathology. From the observation of a testicular lymphoma associated with Epstein-Barr virus in a HIV + patient, we review 19 cases of testicular tumor in HIV + patients previously published in the literature. These tumors are either lymphomas (4 cases) or germ cell tumors (15 cases). Their diagnosis was not difficult, although in the first stages enlarged and painful testicles are often wrongly identified as orchiepididymitis and treated as such. Therapy management proves to be delicate as a result of the significant tumor spread seen in these patients with dysfunctional immune systems. Regarding lymphomas, a low-dose multiagent chemotherapy with intrathecal chemotherapy was recommended by Levine. Concerning germ cell tumors, Wilson prefers an instant aggressive treatment with retroperitoneal lymphadenectomy (whether or not combined with chemotherapy) to avoid the risk of recurrence. In fact, tumor relapses will be difficult to control in the progressive stages of immunodeficiency syndrome.

[Lymphangiomyomatosis: an exceptional cause of chyluria. Report of a case]. / La lymphangiomyomatose: une cause exceptionnelle de chylurie. A propos d'un cas.

A rare case of lymphangiomatosis without pulmonary involvement is reported. The diagnosis was based on the presence of multifocal lesions and histological examination. Retroperitoneal lesions were responsible for chyluria, which was treated surgically. Chyluria is an exceptional complication of this disease, as only 3 such cases have been reported in the literature. The presence of cutaneous signs raises the question of the relations between lymphangiomatosis and Bourneville's tuberous sclerosis.

[Aortic thrombosis during acute endocarditis caused by Staphylococcus aureus]. / Thrombose de l'aorte au cours d'une endocardite aiguë à staphylocoque doré.

The authors report a case of acute bacterial (Staphylococcus aureus) endocarditis in a 70-year-old woman, revealed by a febrile cerebral ischemic accident. Ultrasonography confirmed the presence of a large posterior mitral valve vegetation interfering with left ventricular filling. The sudden onset of complete paraplegia and acute ischemia of the lower limbs suggested thrombosis of the abdominal aorta, which was confirmed by aortography. These features indicated that a vegetation fragment had migrated, obstructing the aortic bifurcation and causing secondary thrombosis. This led in turn to involvement of the medullary arteries and the onset of paraplegia. Unfortunately, acute renal insufficiency and major left heart failure rapidly developed, and the patient died. Autopsy confirmed the diagnosis of aortic thrombosis with involvement of the renal arteries. Multiple visceral infarcts were noted as well as the large mitral vegetation. This case illustrates the potential severity of systemic embolism complicating endocarditis due to Staphylococcus aureus. The accident was remarkable because of the aortic acute occlusion and the association with paraplegia, an unusual neurologic complication.

Evidence that early acute renal failure may be mediated by CD3- CD16+ cells in a kidney graft recipient with large granular lymphocyte proliferation.

We report here on a patient with a large granular lymphocyte proliferative disease who received a third kidney allograft. This patient presented a lymphocytosis (culminating at approximately 30,000/mm3) with a large proportion (approximately 70%) of CD3- WT31- CD2+ CD16+ lymphocytes. Five days after a kidney graft and during prophylactic treatment by Ortho pan OKT3, he presented an acute graft failure with an apparent interruption of graft blood flow as assessed by the Tc99 scan pattern and an arteriogram. The biopsy showed an abnormal accumulation of intravascular CD3- CD16+ cells bound to endothelial cells with thrombilike patterns in small and middle-sized arteries, whereas CD3+ mononucleated cells infiltrate was restricted to interstitium as observed in his previous graft, performed before the appearance of the lymphoproliferative disorder. The syndrome resolved spontaneously. The role of OKT3-mediated release of cytokines able to upregulate endothelial cell adhesion molecules in triggering this phenomenon is discussed.