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Background: Due to increased risk of pyelonephritis, patients with intestinal reconstruction of the lower urinary tract (IRLUT) have long been advised against kidney transplantation. The aim of this study was to compare the outcomes of transplantation between patients with IRLUT and patients with normal LUT (NLUT) using propensity score matching method., Methods: The study included 23 kidney recipients with IRLUT matched to 46 kidney recipients with NLUT using known allograft survival and pyelonephritis risk factors as covariates. One-, 5-, and 10-year graft survival, pyelonephritis, and surgical complications occurrence and graft function were compared., Results: One-, 5-, and 10-year graft survival were 96%, 91%, and 63% in the IRLUT group and 96%, 88%, and 70% in the NLUT group, respectively ( p  = 0.72). Patients with IRLUT had increased cumulative risk of pyelonephritis at 10 years (70% vs. 19%; log-rank < 0.01) without impacting graft function or rejection occurrence. There was no difference in overall surgical complication, but patients with IRLUT had more urological complications than patients with NLUT (62% vs. 28%; p  < 0.01)., Conclusions: Our case-control study consolidates the results regarding the safety of transplantation in patients with IRLUT using a strong validated matching method and provides new insights regarding graft function, pyelonephritis, and surgical complications in this population., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Introduction: The shortage of kidney transplants encourages the expansion of the limits of eligibility criteria for donation. Many donors who are brain dead display acute renal failure at the time of death; is this a real contraindication to harvesting? The aim of this study was to assess kidney graft survival from donors after brain death with confirmed acute renal failure, with or without anuria previous donation., Materials and Methods: All of the transplants performed in two university hospitals between 2010 and 2017 were analyzed retrospectively. All patients who underwent single kidney transplant from a brain-dead donor with acute renal failure (ARF) were included in this study. ARI was defined here by a decrease over 50 % of glomerular filtration rate (GFR) to a threshold below 45mL/min/1.73 m 2  at the time of kidney procurement. Kidney graft survival, incidence of delayed graft function (DGF) and the GFR at 12 months were analyzed. Analysis of kidney transplant survival based on pre-implantation biopsies was additionally done., Results: One hundred and sixty four patients were transplanted with a kidney from donor with ARF during the selected period. At the admission in ICU the average GFR was 67,7±19mL/min/1,73m 2 . At the time of donation, the average age of donors was 56.4±17.7 years, the GFR was 33.7±8.0mL/min/1.73 m 2 16 % of donors were anuric. Cold ischemia time (CIT) was 16.8±5.0hours. The average age of recipients was 55.6±14.1 years. 81 % of the cases were primary transplants. Graft function took place within 7.8±9.4 days after transplantation. There were two non-primary functions (PNF). One hundred and fifty two patients (93 %) had a functional graft at 12 months. The mean GFR at 12 months was 46.8±20.1mL/min/1.73 m 2  and 122 patients (73 %) had a GFR greater than 30mL/min/1.73 m 2 . Seventy-one percent of preimplantation biopsies revealed acute tubular necrosis (ATU); no cortical necrosis was observed. Survival of theses grafts was 85 %, comparable to the total population of study (P=0,21) CONCLUSION: The acute renal failure of the brain-dead donor should not alone be systematically a contraindication to harvesting and kidney transplantation., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: To define guidelines for the management of renal cell carcinoma of the native kidney (NKRCC) in kidney transplant (KTx) recipients and renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients candidates for renal transplantation., Method: A review of the literature following a systematic approach (Medline) was conducted by the CTAFU to report renal cell carcinoma epidemiology, screening, diagnosis and management in KTx candidates and recipients. References were assessed according to a predefined process to propose recommendations with the corresponding levels of evidence., Results: ESRD patients are at higher risk of RCC with a standardized incidence ratio of approximately 4,5 as compared with general population. NKRCC tumors occur in 1 to 3 % of KTx recipients with a 10 to 15-fold increased risk as compared with general population, especially in patients with acquired multicystic kidney disease. Most authors suggest yearly monitoring of the native kidneys using ultrasound imaging. Radical nephrectomy (either open or laparoscopic approach) is the preferred treatment of NKRCC in KTx recipients and RCC in ESRD. Surveillance in a valid option in small or cystic renal masses. In the localized setting, change in immunosuppressive therapy is not recommended besides perioperative avoidance of mTOR inhibitor to limit morbidity. CTAFU does not recommend a mandatory waiting time after nephrectomy for RCC in ESRD patients candidates for renal tranplantation when tumor stage

Objective: To propose surgical recommendations for urothelial carcinoma management in kidney transplant recipients and candidates., Method: A review of the literature (Medline) following a systematic approcah was conducted by the CTAFU regarding the epidemiology, screening, diagnosis and treatment of urothelial carcinoma in kidney transplant recipients and candidates for renal transplantation. References were assessed according to a predefined process to propose recommendations with levels of evidence., Results: Urothelial carcinomas occur in the renal transplant recipient population with a 3-fold increased incidence as compared with general population. While major risk factors for urothelial carcinomas are similar to those in the general population, aristolochic acid nephropathy and BK virus infection are more frequent risk factors in renal transplant recipients. As compared with general population, NMIBC in the renal transplant recipients are associated with earlier and higher recurrence rate. The safety and efficacy of adjuvant intravesical therapies have been reported in retrospective series. Treatment for localized MIBC in renal transplant recipients is based on radical cystectomy. In the candidate for a kidney transplant with a history of urothelial tumor, it is imperative to perform follow-up cystoscopies according to the recommended frequency, depending on the risk of recurrence and progression of NMIBC and to maintain this follow-up at least every six months up to transplantation whatever the level of risk of recurrence and progression. Based on current data, the present recommendations propose guidelines for waiting period before active wait-listing renal transplant candidates with a history of urothelial carcinoma., Conclusion: The french recommendations from CTAFU should contribute to improve the management of urothelial carcinoma in renal transplant patients and renal transplant candidates by integrating both oncologic objectives and access to transplantation., (Copyright © 2020. Published by Elsevier Masson SAS.)

The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: To describe the technique and report our first experience of robotic-assisted renal transplantation (RART) with more than one year follow up., Patients and Methods: In our center the first case of RART was realized in October 2013 with a cadaveric graft. We used the combined extra- and intraperitoneal robot assisted laparoscopic route with extraperitoneal positioning of the graft and intraperitoneal transplantation. The patient was placed in the supine position with arms along the body; the robot came from the right inferior part of the patient. Access to the retroperitoneal space was obtained using an Alexis trocar that permitted the insertion of the kidney with ice without losing the pneumoperitoneum. Ports included a 12-mm camera port (placed under the ombilicus), two 8-mm robotic ports (placed 6cms laterally from the previous port) and a 12-mm assistant port (placed between the upper port and the ombilic). All the pre-, per- and postoperative data were prospectively included in a database. We report the results of the initial experience of RART, performed with more than one year follow-up., Results: This technique is the first described using the retroperitoneal approach that is the routine approach for conventional open renal transplantation. This approach permitted to perform excellent arterial, veinous and ureteral anastomosis. Eight cases of RART were conducted between October 2013 and November 2015 (five men and three women). The average age was 58 years (range 39-75years). The average body mass index was 28 (range 22-38). Five patients had history of abdominal surgery and were dialyzed for 30 months on average (range 3-63months). Three left and five right cadavers kidneys were transplanted in the right iliac fossa. The mean graft size was 109mm (range 90-130). The mean length of the incision for insertion of the graft was 60 mms (40-100mms). Mean warm ischemia time was 63minutes (range 46-84). The total operative time was 200minutes (149-245). No patient was transfused during surgery and two were transfused postoperatively. Median length of hospital stay was 14 days (range 10-30 days). Only one patient needed postoperative morphine, the pain visual analogic scale 12hours postoperatively was 2 (0-5). Mean serum creatinine at seven days, at three months and at one year was 400 (98-639micromol/L), 151 (80-235micromol/L) and 129 (86-194micromol/L) respectively. At one year follow-up, no patient had a wound infection or incisional hernia. One patient was re-operated for ureteral anastomosis stricture., Conclusion: The retroperitoneal approach for RART permits the kidney to be cooled and a direct access to the iliac vessels and bladder. This initial series with more than a year of post-monitoring RART shows promising results despite some initial technical difficulties. The procedure can still be improved and hoped to see an improvement in the results. A comparison to the results of the conventional route is necessary before diffusing the robot-assisted technique., Level of Proof: 3., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: Renal transplantation is performed only in university hospital centres, in accredited transplanting centres. The aim of this study is to analyse the learning curve of this operation and its impact on the graft survival., Patients-Methods: Monocentric retrospective study in which 3 groups have been defined: Juniors 1, Juniors 2 and Seniors corresponding respectively to the first thirty transplantations and to the last thirty transplantations of 5 clinical leaders, and 30 transplantation graft of referent seniors. Data have been registered in a database. Operation times, lukewarm ischemic times and postoperative complications have been compared within the 3 groups., Results: A clear difference of operation time has been noted within the 3 groups with an average time of 202 minutes for Juniors 1, 173 minutes for Juniors 2 and 140 minutes for Seniors (P<0.0001). Likewise, concerning lukewarm ischemic time and vascular anastomosis time respectively with an average time of 72, 59 and 40 min (P<0.0001). Vascular complications occurred in 20% of cases in Juniors 1, 44.3% of cases in Juniors 2 and 17% of cases in Seniors (P=0.65). There were no significant differences of survival without urinary complications: 20% of complications for Juniors 1, 10% for Juniors 2 and 17% for Seniors (P=0.63). Similarly results have been obtained with analysing complications following Clavien's order., Conclusion: This study reveals that renal transplantations operated by young surgeons require longer operation and lukeward ischemic time but without significant repercussions on the surgical complication rate and the global survival. This stresses on the importance of surgical training during medicine internship., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The identification of migration routes, wintering grounds and stopover sites are crucial issues for the understanding of the Palearctic-African bird migration system as well as for the development of relevant conservation strategies for trans-Saharan migrants. Using miniaturized light-level geolocators we report a comprehensive and detailed year round track of a granivorous trans-Saharan migrant, the European Turtle Dove (Streptopelia turtur). From five recovered loggers, our data provide new insights on migratory journeys and winter destinations of Turtle Doves originating from a breeding population in Western France. Data confirm that Turtle Doves wintered in West Africa. The main wintering area encompassed Western Mali, the Inner Delta Niger and the Malian/Mauritanian border. Some individuals also extended their wintering ranges over North Guinea, North-West of Burkina Faso and the Ivory-Coast. Our results reveal that all individuals did not spend the winter period at a single location; some of them experienced a clear eastward shift of several hundred kilometres. We also found evidence for a loop migration pattern, with a post-breeding migration flyway lying west of the spring route. Finally, we found that on their way back to breeding grounds Turtle Doves needed to refuel after crossing the Sahara desert. Contrary to previous suggestions, our data reveal that birds used stopover sites for several weeks, presumably in Morocco and North Algeria. This later finding is a crucial issue for future conservation strategies because environmental conditions on these staging areas might play a pivotal role in population dynamics of this declining species.

De novo tumors in renal allografts are rare and their prevalence is underestimated. We therefore analyzed renal cell carcinomas arising in renal allografts through a retrospective French renal transplant cohort. We performed a retrospective, multicentric survey by sending questionnaires to all French kidney transplantation centers. All graft tumors diagnosed after transplantation were considered as de novo tumors. Thirty-two centers participated in this study. Seventy-nine tumors were identified among 41 806 recipients (Incidence 0.19%). Patients were 54 men and 25 women with a mean age of 47 years old at the time of diagnosis. Mean tumor size was 27.8 mm. Seventy-four (93.6%), 53 (67%) and 44 tumors (55.6%) were organ confined (T1-2), low grade (G1-2) and papillary carcinomas, respectively. Four patients died of renal cell carcinomas (5%). The mean time lapse between transplantation and RCC diagnosis was 131.7 months. Thirty-five patients underwent conservative surgery by partial nephrectomy (n = 35, 44.3%) or radiofrequency (n = 5; 6.3%). The estimated 5 years cancer specific survival rate was 94%. Most of these tumors were small and incidental. Most tumors were papillary carcinoma, low stage and low grade carcinomas. Conservative treatment has been preferred each time it was feasible in order to avoid a return to dialysis., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: Transplantation Committee of the French Association of Urology (CTAFU) conducted a review of the complication of kidney transplantation in obese recipients., Material and Methods: A bibliographic research in French and English using Medline with the keywords "obesity", "body mass index", "kidney transplantation", "graft function", "survival", "wound complications", "graft rejection" and "graft survival" was performed. We limited the review for the last fifteen years because of the change in immunosuppressive treatment area. Only studies with more than 20 obese patients were selected., Results: Wound or infectious postoperative complications and delayed graft function are more frequent in obese patients than in non-obese recipients. Similarly, transplant survival at 5 years is lower in obese patients. On the other hand, patient survival and acute rejection are the same between the two groups if recipient selection is carefully made, particularly with regard to heart complication., Conclusion: Kidney transplantation in obese patients is not an easy surgery with known complication. Obese patients will take time before transplantation to explain all the risk and a regular heart follow-up is crucial if we don't want to reduce patient survival. But obese survival is better if we proceed to kidney transplantation than if they stay on dialysis, arguing for a non-exclusion of the waiting list. So there is the need for a national study concerning obese patients on waiting list to enact future guidelines., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aim: Laparoscopic pelvic lymphadenectomy in localized prostatic cancer is performed since the 1990s, lessens the postoperative complications and respects carcinologic's principles (No. lymph nodes removed and lymph nodes metastasis). In order to verify that these objectives are achieved, we compared our results of pelvic lymphadenectomy by laparotomy and by laparoscopy for the past 12 years., Patients and Methods: Between January 1997 and June 2008, 36 (23.8%) patients underwent open pelvic lymphadenectomy and 76.16% (115 cases) laparoscopic pelvic lymphadenectomy. We did a retrospective and comparative analysis of data including the preoperative characteristics, per- and postoperative complication as well pathologic results., Results: Preoperative data were comparable between both groups. The comparison of the peroperative data showed an increased bleeding volume in the open group (105.6±420.9mL; 12.1±96.1mL: P=0.001) and longer operative time in the laparoscopic group (103.7±83.9min; 132.8±40.9min: P=0.006). Postoperative complications were similar. Pathologic results showed a significantly more important number of lymph nodes removed in the open group (7.2±3.5; 5.7±3.2: P=0.022), but the positive rate similar in both groups (13.9%; 22.6%: P=0.258). In order to remove "the learning curve effect", we compared 36 open pelvic lymphadenectomy to the last 36 laparoscopic pelvic lymphadenectomy. In the laparoscopic group the patients showed an upper Gleason score (6.3±1.1; 7±1: P=0.005); but there was no difference for the operative time, number of lymph nodes removed and the complications rates., Conclusions: After training, laparoscopic pelvic lymphadenectomy was similar to open pelvic lymphadenectomy., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objectives: To identify the risk factors for ureteral stenosis after renal transplantation and to evaluate their impact on both graft and patient survival., Patients and Methods: This retrospective study included 789 kidney transplants among 782 patients performed at our institution between 1995 and 2007. The parameters studied included the characteristics of the donor, recipient and transplant, the surgical variables, the elements of the monitoring process and a graft and patient survival., Results: The ureteral stenosis rate after renal transplantation was found to be 6.5%, and the ureterovesical junction was the most common location (68%). A univariate analysis showed that this complication was significantly associated with a higher donor age (P=0.01), abnormal graft revascularisation (P=0.032) and DGF (Delay Graft Function) (P=0.05). In multivariate analysis, only donor age (P=0.001) and abnormal graft revascularisation (P=0.035) were independent risk factors for ureteral stenosis after renal transplantation. When ureteral stenosis was treated, an analysis of the survival curves according to the Kaplan-Meier method did not reveal significant differences either in graft survival (P=0.518) or overall survival of the patients (P=0.614) as compared to the control group., Conclusions: In the present study, donor age and abnormal graft revascularisation were independent risk factors for ureteral stenosis after renal transplantation. This result is a strong argument for an ischemic component in the genesis of ureteral stenosis after renal transplantation, which should help to identify patients at risk., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: Radial-cephalic fistulas (RCFs) perianastomotic stenoses (PASs) are on and around the fistula anastomosis. This group of lesions encompasses juxta-anastomotic stenosis (stenosis located on the venous side within 3 cm away from the anastomosis), anastomotic, and arterial stenosis. The purpose of our study was to assess the postintervention primary patency and assisted postintervention primary patency (APP) rates for surgery and angioplasty when treating these stenoses. The secondary endpoint was to identify factors that might influence the procedure's patency rates., Materials and Methods: This retrospective study included 73 consecutive patients treated for lack of maturation PASs between January 1999 and December 2005 in two interventional centers. Patients' mean age was 65 years old. Stenoses were treated by surgery (n = 21) or percutaneous transluminal angioplasty (PTA; n = 52). Surgery meant creation of a new anastomosis excluding the area of stenosis. Preoperative characteristics including the patient's age, gender, comorbidities, stenosis location, and length were not statistically different between the two groups. The mean follow-up was 39 months for PTA and 49 months for surgery., Results: Anatomical and clinical success rates were 86% and 90% for surgery, and 75% and 92% for PTA. At 1 year, the primary patency rates were 71 ± 10% for surgery and 41 ± 6% for PTA, respectively (P < .02). There was no significant difference between the two groups with respect to assisted primary patency (95% vs 92%). In the PTA group, stenosis location at the anastomosis itself was a risk factor of early recurrence (P = .047). The complication rate was similar between surgery and PTA., Conclusion: Our results suggest that the treatment of anastomotic stenoses should be surgical rather than endovascular. Angioplasty and surgery have shown similar results when used to treat other perianastomotic stenoses, but repeat procedures were more frequent with angioplasty., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

The objective of this study was to assess the value of a urine bacterial culture performed before prostate biopsy. We performed a prospective study on 353 patients who underwent prostate biopsy. All patients had a urine bacterial culture performed before biopsy. We compared the outcomes of patients with bacteriuria (left untreated) with those of patients without bacteriuria. Of the 353 men, 12 had a pre-biopsy-positive bacterial culture and underwent prostate biopsy without any infectious complication. Fifteen patients with a negative pre-biopsy culture developed a post-biopsy-positive bacterial culture, but remained asymptomatic without any treatment. Only four men from the group without pre-biopsy bacteriuria developed an infectious complication, requiring 3 weeks of antibiotic therapy. The complication rates were similar for both groups. Our results suggest that routine urine bacterial culture before prostate biopsy is not useful when antibiotic prophylaxis and enema are performed. We do, however, suggest performing a urine bacterial culture before prostate biopsy for patients with a previous history of urinary tract infections.

Background: Delayed maturation of radial-cephalic fistulas can be due to lesions of the radial artery that are amenable to percutaneous dilation., Methods: Over a period of 7 years, 74 consecutive patients underwent angiography of an immature fistula that showed either stenosis or an insufficient enlargement of the radial artery that was treated by percutaneous dilation. Success, complications and secondary interventions were recorded according to consensus definitions. Patency following angioplasty was estimated with the Kaplan-Meier technique., Results: The mean patient age was 70 years, 44% were women, 69% had diabetes, 23% were smokers, 76% had hypertension, 64% had coronary disease and 46% had peripheral artery occlusive disease. Concomitant venous stenosis was diagnosed in 53% of patients. Arterial stenosis was >5 cm long in 53 cases. Technical success was achieved in 73/74 cases following angioplasty. All but two fistulas were then successfully used for dialysis. Dilation-induced rupture occurred in 13 cases (17%) but required only two stent placements. Five cases (7%) of hand ischaemia within 1 month of dilation were treated successfully by ligation of the distal artery. Primary patency rates at 12 and 24 months were significantly better for pure arterial lesions, with 65% and 61% compared to 42% and 35% in cases of concomitant venous stenosis (P < 0.04). The secondary patency rates were 96% and 94% at 1 and 2 years, respectively., Conclusion: Dilation of the radial artery yields higher patency rates than for veins. Surgeons might therefore be less demanding about the initial quality of the radial artery prior to creation of radial-cephalic fistulas.

Objective: Perianastomotic stenoses (PAS) complicating native arteriovenous fistulas (AVF) of the forearm can be treated by angioplasty or surgery. The objective of this study was to report primary patency (PP) and primary assisted patency (PAP) rates of surgery and angioplasty of these stenoses. The secondary objective was to identify factors influencing the patency rates of these reoperations., Material and Methods: Seventy-three patients with a mean age, 65 years were treated for PAS between January 1999 and December 2005 in two centres (Tours and Le Mans), which were retrospectively included. PAS were treated by surgery (n=21) or angioplasty (n=52). The two groups were comparable. The mean follow-up was 39 months for the angioplasty group and 49 months for the surgery group (p=0.088)., Results: The PP rate was 71+/-10% for surgery and 41+/-6% for angioplasty (p<0.0175). The PAP rate was not significantly different (p=0.462) between angioplasty (92+/-4%) and surgery (95+/-4%). In the endovascular group, the site of stenosis on the anastomosis was a risk factor for early recurrence (95% CI between 0.006 and 0.392; p=0.047)., Conclusion: These results suggest that anastomotic stenoses should be treated surgically rather than by angioplasty. Angioplasty and surgery give identical patency rates in other types of perianastomotic stenoses at the cost of a higher reoperation rate for angioplasty.

Study Objective: The objective of this prospective study was to describe the nature of the lesions observed during brain-dead cadavre donor kidney harvesting in France and to identify the risk factors for these lesions., Material and Methods: A questionnaire elaborated by the AFU Transplantation Committee concerning the quality of kidneys harvested from cadavre donors was sent to all centres performing renal transplantation in France in 2000. This prospective study was conducted over a period of 1 year and concerned the overall multi-organ harvesting procedure based on all data concerning the renal parenchyma, arteriovenous and ureteric characteristics, and the outcome of the transplants., Results: Twelve centres completed the survey, allowing analysis of the data of 201 donor kidneys. 91% of harvesting surgeons were urologists. Various incidents were reported during 11% of harvesting procedures, but 1/3 of the abnormalities were not recorded by the harvesting surgeon. Isolated kidney harvesting was found to be a risk factor (20% vs 8.6%). The rate of parenchymal abnormalities was 50%, 2/3 of which were related to inadequate removal of perirenal fat. Atheroma was a risk factor for arterial lesions during harvesting (21% vs 6.50). Venous abnormalities were detected in 9% of cases: 89% of them were due to the harvesting procedure and 59% of them were not identified by the harvesting surgeon. The fact of not being a transplant surgeon was a risk factor for venous lesions (21.9% vs 6.5%). 4% of ureteric lesions were observed with no consequence on graft outcome., Conclusion: Adequate removal of perirenal fat before conditioning is not acquired. Isolated kidney harvesting and atheroma were risk factors for parenchymal and arterial lesions, respectively. Venous harvesting anomalies were more frequent among non-transplant surgeons.

Nuclear orphan receptors are known to be important mediators of neurogenesis, but the target genes of these transcription factors in the vertebrate nervous system remain largely undefined. We have previously shown that a 500-base pair fragment in the first intron of the GRIK5 gene, which encodes the kainate-preferring glutamate receptor subunit KA2, down-regulates gene expression. In our present studies, mutation of an 11-base pair element within this fragment resulted in a loss of nuclear protein binding and reverses negative regulation by the intron. Using yeast one-hybrid screening, we have identified intron-binding proteins from rat brain as COUP-TFI, EAR2, and NURR1. Gel shift studies with postnatal day 2 rat brain extract indicate the presence of COUP-TFs, EAR2, and NURR1 in the DNA-protein complex. Competition assays with GRIK5-binding site mutations show that the recombinant clones exhibit differential binding characteristics and suggest that the DNA-protein complex from postnatal day 2 rat brain may consist primarily of EAR2. The DNA binding activity was also observed to be enriched in rat neural tissue and developmentally regulated. Co-transfection assays showed that recombinant nuclear orphan receptors function as transcriptional repressors in both CV1 cells and rat CG4 oligodendrocyte cells. Direct interaction of the orphan receptors with and relief of repression by TFIIB indicate likely role(s) in active and/or transrepression. Our findings are thus consistent with the notion that multiple nuclear orphan receptors can regulate the transcription of a widely expressed neurotransmitter receptor gene by binding a common element in an intron and directly modulating the activity of the transcription machinery.

Time- and sex-specific summer survival of roe deer fawns was estimated using capture-mark-recapture methods in two enclosed populations living in contrasting conditions. The population of Trois Fontaines (eastern France) was roughly constant in size throughout the study period, while in Chizé (western France), the population experienced frequent summer droughts and numbers decreased continuously during the study. Early survival of fawns was low and highly variable over the years at both Chizé and Trois Fontaines, and demonstrated marked variations between cohorts that need to be taken into account when modelling roe deer population dynamics. In Trois Fontaines, fawn survival was positively correlated with early body growth and total rainfall in May and June. In Chizé, fawn survival decreased with increasing density and tended to increase with increasing rainfall in May and June and adult female body mass. These factors explained more than 75% of the variability in early survival observed in both populations. Variation between cohorts had different consequences for the two populations. At Trois Fontaines, cohort variation was limited to a numerical effect on early survival. However at Chizé, cohort variation was long-lasting and affected the phenotypic quality of survivors at later ages, and thereby future survival and breeding abilities (both numerical and quality effects). Male and female fawns had similar survival over their first summer in both populations. This result contrasts with the lower survival of young males often observed in ungulates. Two ultimate causes can be proposed to account for the low and variable survival of roe deer fawns over the first summer: the high energy expenditures incurred by does during each breeding attempt and/or the low absolute body size of newborn roe deer fawns.

Retinoic acid (RA), an important regulator of cell differentiation, is biosynthesized from retinol via retinal by a two-step oxidation process. We previously reported the purification and partial amino acid (aa) sequence of a rat kidney aldehyde dehydrogenase (ALDH) isozyme that catalyzed the oxidation of 9-cis and all-trans retinal to corresponding RA with high efficiency [Labrecque et al. Biochem. J. 305 (1995) 681-684]. A rat kidney cDNA library was screened using a 291-bp PCR product generated from total kidney RNA using a pair of oligodeoxyribonucleotide primers matched with the aa sequence. The full-length rat kidney ALDH cDNA contains a 2315-bp (501 aa) open reading frame (ORF). The aa sequence of rat kidney ALDH is 89, 96 and 87% identical to that of the rat cytosolic ALDH, the mouse cytosolic ALDH and human cytosolic ALDH, respectively. Northern blot and RT-PCR-mediated analysis demonstrated that rat kidney ALDH is strongly expressed in kidney, lung, testis, intestine, stomach and trachea, but weakly in the liver.

The screening of a size-selected cDNA library from the ovary revealed the existence of a second form of PRL receptor in the rat. The polypeptide sequence deduced from cDNAs has a much longer cytoplasmic domain (357 amino acids) than the form previously identified in the liver (57 amino acids). Nucleotide sequence analysis and comparison with rabbit, mouse, and human PRL receptor cDNAs suggests that the two forms of rat PRL receptor result from alternative splicing of a primary transcript. Complementary DNAs encoding the long form of the receptor were also found in a library prepared from estradiol-treated rat liver, although they represent a minor fraction of total PRL receptor cDNAs obtained from this tissue. DNA polymerase chain reaction amplification of cDNA confirmed the presence of the two receptor forms in both the ovary and liver. Northern analysis, using probes that specifically hybridize with either form of mRNA, indicates a major transcript of 1.8 kilobases (kb) in estradiol-treated liver, which encodes the receptor with a short cytoplasmic domain, while the long form of the receptor is encoded by mRNAs of 2.5 and 3 kb. In the ovary, a complex pattern of hybridization to multiple mRNAs (1.8-5.5 kb) is obtained with the probe specific to the long form, and essentially only a 5.5-kb mRNA is obtained with the probe specific to the short form. The predicted size of the mature form of the long PRL receptor (PRL-R2) is 591 amino acid residues.(ABSTRACT TRUNCATED AT 250 WORDS)

The rat liver prolactin receptor has been purified to homogeneity, and partial amino acid sequences have been obtained. The structure of the receptor has been deduced from a single complementary DNA clone. The mature protein of 291 amino acids has a relatively long extracellular region, a single transmembrane segment, and a short (57 amino acids) cytoplasmic domain. With the rat cDNA used as a probe, the prolactin receptor in rabbit mammary gland and human hepatoma cells has also been isolated. These tissues contain a second, longer form of the receptor (592 and 598 amino acids, respectively). Both the short and long forms of the prolactin receptor show regions of strong sequence identity with the human and rabbit growth hormone receptors, suggesting that the prolactin and growth hormone receptors originate from a common ancestor.

Sex steroids are major regulators of PRL receptor expression in rat liver. Using a probe encoding the rat PRL receptor we have studied receptor mRNA levels in female rat liver during ontogeny and in response to estrogen treatment. Steady state mRNA levels were determined by Northern blot and densitometric analysis. Messenger RNA levels have been compared to the number of binding sites, which was assessed by Scatchard analysis of [125I]ovine PRL binding in membrane preparations. Our results show that steady state mRNA and binding levels of PRL receptors are both regulated by development and estrogens, but that binding does not exactly parallel mRNA levels. From the developmental stages of prepuberty to adult, receptor numbers increase 8-fold, whereas mRNA levels increase 3-fold. Estrogen treatment stimulates receptor levels 6-fold, but mRNA levels are only increased 3-fold. These results suggest that PRL receptor gene expression in rat liver is regulated at the transcriptional or posttranscriptional level as well as at the translational level.

Two lambda gt11 clones containing fragments of cDNA encoding the prolactin receptor from rabbit mammary gland were isolated using a rat liver prolactin receptor cDNA probe. An 1848-base-pair open reading frame encodes a mature prolactin-binding protein of 592 amino acids that contains three domains: (i) the extracellular, amino-terminal, prolactin-binding region of 210 residues; (ii) the transmembrane region of 24 residues; and (iii) the intracellular, carboxyl-terminal domain of 358 residues. This latter domain is much longer than the cytoplasmic domain (57 residues) previously described for the rat liver prolactin receptor. In addition, the sequence identity of this form of prolactin receptor with the growth hormone receptor is extended in the cytoplasmic domain.

Human PRL receptor cDNA clones from hepatoma (Hep G2) and breast cancer (T-47D) libraries were isolated by using a rat PRL receptor cDNA probe. The nucleotide sequence predicts a mature protein of 598 amino acids with a much longer cytoplasmic domain than the rat liver PRL receptor. Although this extended region has additional segments of localized sequence identity with the human GH receptor, there is no identity with any consensus sequences known to be involved in hormonal signal transduction. This cDNA will be a valuable tool to better understand the role of PRL in the development and growth of human breast cancer.