Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways.

Mitochondria are highly dynamic organelles that can change in number and morphology during cell cycle, development or in response to extracellular stimuli. These morphological dynamics are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Genetic approaches have identified a cohort of conserved proteins that form the core of mitochondrial remodelling machineries. Mitofusins (MFNs) and OPA1 proteins are dynamin-related GTPases that are required for outer- and inner-mitochondrial membrane fusion respectively whereas dynamin-related protein 1 (DRP1) is the master regulator of mitochondrial fission. We demonstrate here that the Drosophila PMI gene and its human orthologue TMEM11 encode mitochondrial inner-membrane proteins that regulate mitochondrial morphogenesis. PMI-mutant cells contain a highly condensed mitochondrial network, suggesting that PMI has either a pro-fission or an anti-fusion function. Surprisingly, however, epistatic experiments indicate that PMI shapes the mitochondria through a mechanism that is independent of drp1 and mfn. This shows that mitochondrial networks can be shaped in higher eukaryotes by at least two separate pathways: one PMI-dependent and one DRP1/MFN-dependent.

Ureteral necrosis after kidney transplantation: risk factors and impact on graft and patient survival.

BACKGROUND: Ischemia, the main cause of ureteral necrosis in renal transplantation, cannot alone explain the late occurrence of some fistulas beyond the first postoperative month. The aim of this study, performed on a cohort of 1,629 consecutive kidney transplantations, was to analyze the risk factors implicated in the occurrence of ureteral necrosis and its impact on graft and patient survival. METHODS: Between January 1990 and December 2001, 1,629 renal transplantations were performed in the authors' center. All biologic and clinical data were computerized in a cross-audited and validated data bank (Données Informatisées et Validées en Transplantation). The parameters studied were donor age, gender, cause of death and serum creatinine before procurement; and recipient age, gender, initial disease, panel reactive antibody, retransplantation, cold ischemia time, delayed graft function, human leukocyte antigen incompatibilities, induction and maintenance immunosuppression, right or left kidney, number of arteries, site of transplantation and the presence or not of a double-J stent. The follow-up parameters were the number and timing of acute rejection episodes, cytomegalovirus (CMV) infection (viremia, polymerase chain reaction), and acute pyelonephritis. Ureteral histologic analysis was performed in 25 cases (necrosis, leukocyte infiltration, and CMV or BK virus inclusions). Uni- and multivariate statistical tests were used (alpha risk at 5%). All of the patients with ureteral necrosis had undergone neoureterocystostomy or ureteral anastomosis with the native ureter but with a systematic double-J stent. RESULTS: Ureteral necrosis occurred in 52 of the 1,629 patients (3.2%) and was significantly and independently correlated with donor age (P=0.041) and delayed graft function (P=0.016). CMV infections were also higher in the necrosis group (P=0.001), but donor CMV status was not statistically different between the two groups (36.2% vs. 36.7%). Ureteral histologic studies showed CMV and BK virus inclusions in 4 and 2 cases, respectively, and arterial and venous thrombosis in 4 and 16 cases, respectively. No pattern of ureteral rejection was observed. Ureteral necrosis did not affect the 10-year patient and graft survival, which were 87% and 66%, respectively, for the necrosis group and 86% and 58%, respectively, for the control group (P=not significant). CONCLUSIONS: The authors' data provide new information concerning a classic surgical complication after kidney transplantation. The link they have identified between the occurrence of ureteral necrosis, donor age, and delayed graft function reemphasizes the interdependence between surgical and medical complications in kidney transplantation.

[Results and surgical complications of pancreas transplantation with enteric exocrine drainage]. / Résultats et complications chirurgicales de la transplantation pancréatique avec dérivation intestinale.

INTRODUCTION: The objective of this study was to evaluate the results and surgical complications of total pancreas transplantation with enteric exocrine drainage since the beginning of our experience with this type of transplantation. PATIENTS AND METHODS: From November 1999 to December 2002, 62 total pancreas transplantations were performed, consisting of 51 combined kidney-pancreas transplantations, 10 after renal transplantation and 1 pancreas-liver transplantation. Kidneys and pancreases were washed and stored in either Belzer solution or Celsior solution. Transplantation was performed via a midline transperitoneal incision with venous anastomosis at the root of the inferior vena cava (54 cases) or, more recently, in the superior mesenteric vein (8 cases). The arterial anastomosis was then performed in the right common iliac artery. Exocrine drainage was performed by side-to-side anastomosis between the donor duodenum and the recipient jejunum. The kidney was transplanted onto the left external iliac vessels and was extraperitonealised. RESULTS: The mean age of the recipients and donors was 41 +/- 9 years and 33 +/- 11 years, respectively. The mean cold ischaemia time was 14 +/- 5 hours. Four pancreases were lost due to venous thrombosis, 1 due to severe pancreatitis with haemodynamic collapse and venous thrombosis and another due to total necrosis of the duodenum. Seventeen patients (27%) were reoperated, including 10 during the first postoperative month and 7 during the first year. No cases of fistula of the gastrointestinal anastomosis were observed. All patients with a functional graft no longer required exogenous insulin. The actuarial patient and graft three-year survival was 96% and 86% respectively. CONCLUSION: Despite their high frequency, surgical complications did not have any harmful effects on either control of diabetes or graft and patient survival.

[Value of the uCyt+ test for the detection and followup of bladder tumors]. / Intérêt du test uCyt+ pour le dépistage et le suivi des tumeurs de vessie.

INTRODUCTION: Superficial bladder tumours are common tumours that frequently relapse, generally with deterioration of the grade. Cystoscopic surveillance is unpleasant for the patient and is associated with considerable morbidity, while urine cytology, although very easy to poor, has a low sensitivity. According to the literature, the uCyt+ test is very effective for the detection of urothelial tumours. This immunofluorescent technique detects desquamated tumour cells previously labelled by specific antibodies. MATERIAL AND METHOD: This prospective study was conducted in 92 patients undergoing screening or follow-up cystoscopy. Voided urine was collected prior to cystoscopy to perform standard cytology and a uCyt+ test. These examinations were interpreted independently under blinded conditions. RESULTS: The sensitivity and specificity of uCyt+ were 68.7% and 81.7%, versus 40.6% and 96.7% for cytology. The sensitivity of uCyt+ was higher for low-grade tumours (87.5%), in contrast with cytology (37.5%). The results of uCyt+ were comparable to those of cytology for high-grade tumours (80%). CONCLUSION: The uCyt+ test presented better performances than standard cytology. It would allow less frequent surveillance cystoscopy examinations, especially in patients with low-grade lesions.

[Suspended congenital ureteral stricture]. / Sténose congénitale suspendue de l'uretère.

The authors report a case of suspended congenital lumbar ureteric stricture in a 20-year-old woman following pyelonephritis with dilatation of the pyelocaliceal cavities. Assessment of this stricture demonstrated a vascular pedicle crossing in front of this zone, but with no signs of compression. Treatment consisted of retroperitoneal laparoscopic resection-anastomosis.

[Endoscopic incision of uretero-vesical junction after renal transplantation]. / Incision endoscopique des sténoses de la jonction urétéro-vésicale après transplantation rénale.

Stenosis of the ureterovesical reimplantation is one of the most frequent urological complications after renal transplantation. It can be treated surgically or endoscopically (dilatation, ureteric stent or Acucise). The authors present the results of a new endoscopic electrode-scalpel incision technique used as first-line treatment in 9 patients with stenosis of the distal centimetre of the ureter.

The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation.

Eukaryotic peptidoglycan recognition proteins (PGRPs) are related to bacterial amidases. In Drosophila, PGRPs bind peptidoglycan and function as central sensors and regulators of the innate immune response. PGRP-LC/PGRP-LE constitute the receptor complex in the immune deficiency (IMD) pathway, which is an innate immune cascade triggered upon Gram-negative bacterial infection. Here, we present the functional analysis of the nonamidase, membrane-associated PGRP-LF. We show that PGRP-LF acts as a specific negative regulator of the IMD pathway. Reduction of PGRP-LF levels, in the absence of infection, is sufficient to trigger IMD pathway activation. Furthermore, normal development is impaired in the absence of functional PGRP-LF, a phenotype mediated by the JNK pathway. Thus, PGRP-LF prevents constitutive activation of both the JNK and the IMD pathways. We propose a model in which PGRP-LF keeps the Drosophila IMD pathway silent by sequestering circulating peptidoglycan.

Management of artificial urinary sphincter dysfunction.

OBJECTIVE: The long-term outcome of artificial urinary sphincter (AUS) is unpredictable because of, among others, the risk of breakdown of one of its components. Our objective was to define a strategy for an accurate diagnosis and an appropriate management of these problems. PATIENTS AND METHODS: From 1985 to 2000, 298 AUS (AMS 800) have been implanted in 288 patients aged 53 +/- 21 years (8 to 87 years). There were 130 women with urinary stress incontinence, 84 with neurological disorders, 76 following prostatic surgery and 8 for other reasons. Diagnosis was often done following the recurrence of urinary incontinence. The pump was systematically checked and all patients underwent radiographic and urodynamic studies. We have systematically looked for the defective component in order to avoid replacing the entire sphincter. RESULTS: Fifty-five patients (19%) have been re-operated on after a median follow-up of 23 months (11 days-10 years): Thirty-two only once, 20 twice and 3 patients 4 times. There were 55 depressurizations, 18 device dysfunctions without depressurization and 11 removals of the sphincter. Among the 55 depressurizations, 30 were related to a perforation of one component, 24 to a functional but insufficient sphincter and 1 to tubing disconnection. In forty cases, only one component of the AUS was replaced while 2 components were replaced in 10 cases, the entire AUS in 4 cases and no component in one case. CONCLUSION: The longer the follow-up the greater is the probability of a dysfunction. We systematically continue to look for the defective component and just to replace it instead of the entire sphincter.

Morbidity of inguinal lymphadenectomy for invasive penile carcinoma.

OBJECTIVE: To determine the incidence and the consequences of complications related to modified and radical inguinal lymphadenectomy in patients with invasive penile carcinoma, defined by invasion of the corpus spongiosum or cavernosum (> or =T2). MATERIALS AND METHODS: A total of 118 modified (67.0%), and 58 radical (33.0%) inguinal lymphadenectomy were performed in 88 patients between 1989 and 2000. To decrease the morbidity, radical inguinal lymphadenectomy was proposed only in patients with palpable inguinal lymph nodes, uni- or bilaterally (N1 or N2). Modified inguinal lymphadenectomy was performed bilaterally in patients with invasive penile carcinoma and non-palpable inguinal lymph nodes (N0), and unilaterally in the side without inguinal metastases in N1 patients. Complications were assessed retrospectively with a median follow-up of 46 months and classified as early (event observed during the 30 days after the procedure) or late (event present after hospitalisation or after the first months). RESULTS: A total of 74 complications after 176 procedures were recorded. After modified inguinal lymphadenectomy, 8 early (6.8%) and 4 late (3.4%) complications were observed. There were a total of 110 dissections with no complications and 8 dissections with 1 or 2 complications. After radical inguinal lymphadenectomy, the morbidity increased with 24 early (41.4%) and 25 late (43.1%) complications, observed in only 18 of 58 radical procedures. Leg oedema was the most common late complication, interfering with ambulation in 13 cases (22.4%). CONCLUSION: Modified inguinal lymphadenectomy, with saphenous vein sparing and limited dissection offers excellent functional outcome in patients with invasive penile carcinoma and nonpalpable inguinal lymph nodes. The morbidity after radical lymphadenectomy still significant, especially in patients with multiple or bilateral superficial inguinal lymph nodes treated by pelvic and bilateral inguinal lymphadenectomy.