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LRP
Selected AbstractsCellular prion protein/laminin receptor: distribution in adult central nervous system and characterization of an isoform associated with a subtype of cortical neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2004Hasna Baloui Abstract The 67-kDa LR protein was originally discovered as a non-integrin laminin receptor. Several more recent in vitro studies demonstrated the function of 67-kDa LR and its related ,precursor' form 37-kDa LRP as receptors of cellular prion protein and their implication in abnormal prion protein propagation in vitro. In addition, expression of both proteins was shown to increase considerably in the brain of scrapie-infected mice and hamsters. While LRP/LR are thus likely to play important roles in neuronal cell adhesion, survival and homeostasis and during pathological disorders, little is known so far about their fine cellular distribution in adult central nervous system. Using immunocytochemistry and western blotting, we show here that the 67-kDa LR is the major receptor form in adult rat brain and spinal cord, expressed within the cytoplasm and at the plasma membrane of most neurons and in a subset of glial cells. The overall distribution of LR correlates well with that reported for laminin-1 but also with brain regions classically associated with prion-related neurodegeneration. In contrast to LR, the 37-kDa LRP form is much less abundant in adult than in postnatal central nervous system. Characterization of a novel antibody allowed us to study the distribution across tissues of cell membrane-associated LRP. Interestingly, this form is almost exclusively found on a subclass of parvalbumin-immunoreactive cortical interneurons known to degenerate during the early stages of Creutzfeldt-Jakob disease. Our demonstration of local differences in the expression of particular LRP/LR isoforms may be a first step towards unraveling their specific molecular interactions. [source] Efficacy of small reconstruction plates in vascularized bone graft mandibular reconstruction,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2006D. Gregory Farwell MD, FACS Abstract Background: Utilization of vascularized bone grafts rigidly fixated with titanium reconstruction plates is the method of choice for reconstruction of segmental mandibular defects. We hypothesized that the use of the newer 2.0-mm locking reconstruction plate (LRP) is not associated with higher rates of complications when compared with larger, previously used plating systems. Methods: A retrospective case series of 184 patients undergoing 185 vascularized bone graft reconstruction procedures of the mandible was conducted. Results: There were 37 plate complications. There was no significant difference in complication rates for the 2 most used plate types (14.5% with the 2.0-mm LRP and 22.2% with the 2.4-mm LRP). Conclusions: Use of the smaller 2.0-mm LRP was not associated with an increase in the complications of plate fracture, exposure, infection, or nonunion. Because of its lower profile and ease of application, the 2.0-mm LRP is our plate of choice for mandibular reconstruction. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] Laparoscopic radical prostatectomy: Transfer validityINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2010Tibet Erdogru Objectives: The impact of a formal fellowship training program on the independent practice of the trainees (i.e. transfer validity) has not been evaluated. We analyzed the transfer validity of a structured curriculum in an in-door as well as an out-door setting. Methods: After completing their training, two fourth generation laparoscopic surgeons who started at the same time compared operative parameters and oncological outcomes in their independent practice, prospectively analyzing the next 100 patients in each. One surgeon continued laparoscopic radical prostatectomy (LRP) in the same center of excellence (Group-In), whereas the other implemented the procedure in a separate academic center (Group-Out). Results: The demographics for both groups (Group-In vs Group-Out) were similar regarding age, prostate volume and preoperative prostate-specific antigen levels. Mean operation times (214.8 vs 224.2 min; P = 0.494) and estimated blood loss (472.4 vs 402.6 mL; P = 0.109) did not differ significantly in both groups as well as complication rate (20 vs 24%), median catheter time (8 vs 8.5 days) and continence rates at 12 months (95 vs 95.5%). According to the pathological stages, the rates of positive surgical margins were similar for pT2 (3.2 vs 4.3%) and pT3 (42.8 vs 45.2%), respectively. Conclusions: With a well designed, long-term preclinical and clinical fellowship training program, LRP techniques can be efficiently transferred from the center of excellence to other centers with no significant impact on surgical, functional and oncological outcomes. [source] Facilitating the technique of laparoscopic running urethrovesical anastomosis using Lapra-ty absorbable suture clipsINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2006YASUMASA SHICHIRI Abstract, We herein describe a simplified technique for performing laparoscopic running urethrovesical anastomosis using Lapra-ty absorbable suture clips (Ethicon, Somerville, NJ, USA) during a laparoscopic radical prostatectomy (LRP). Using two 20 cm absorbable sutures tied together and locked with Lapra-ty at their tail ends, the initiating mattress sutures are placed in the 5:30,6:30-o'clock area between the urethra and the bladder neck. The left and right running sutures are then made clockwise from the 6:30,12-o'clock position and counterclockwise from the 5:30,12-o'clock position, respectively. Both sutures are locked with proper tension by Lapra-ty at the 3, 9 and 12-o'clock positions, and then they are intracorporeally tied together just at the 12-o'clock position. In the initial 20 cases, this anastomosis took 22.5 min on average to perform. We experienced no major urine extravasation and no anastomotic stricture to date. [source] BMP-9-induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/,-catenin signallingJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Ni Tang Abstract Bone morphogenetic protein 9 (BMP-9) is a member of the transforming growth factor (TGF)-,/BMP superfamily, and we have demonstrated that it is one of the most potent BMPs to induce osteoblast differentiation of mesenchymal stem cells (MSCs). Here, we sought to investigate if canonical Wnt/,-catenin signalling plays an important role in BMP-9-induced osteogenic differentiation of MSCs. Wnt3A and BMP-9 enhanced each other's ability to induce alkaline phosphatase (ALP) in MSCs and mouse embryonic fibroblasts (MEFs). Wnt antagonist FrzB was shown to inhibit BMP-9-induced ALP activity more effectively than Dkk1, whereas a secreted form of LPR-5 or low-density lipoprotein receptor-related protein (LRP)-6 exerted no inhibitory effect on BMP-9-induced ALP activity. ,-Catenin knockdown in MSCs and MEFs diminished BMP-9-induced ALP activity, and led to a decrease in BMP-9-induced osteocalcin reporter activity and BMP-9-induced expression of late osteogenic markers. Furthermore, ,-catenin knockdown or FrzB overexpression inhibited BMP-9-induced mineralization in vitro and ectopic bone formation in vivo, resulting in immature osteogenesis and the formation of chondrogenic matrix. Chromatin immunoprecipitation (ChIP) analysis indicated that BMP-9 induced recruitment of both Runx2 and ,-catenin to the osteocalcin promoter. Thus, we have demonstrated that canonical Wnt signalling, possibly through interactions between ,-catenin and Runx2, plays an important role in BMP-9-induced osteogenic differentiation of MSCs. [source] C-terminal 37 residues of LRP promote the amyloidogenic processing of APP independent of FE65JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2008Madepalli K. Lakshmana Abstract The major defining pathological hallmark of Alzheimer's disease (AD) is the accumulation of amyloid , protein (A,), a small peptide derived from ,- and ,-secretase cleavages of the amyloid precursor protein (APP). Recent studies have shown that the Low-density lipoprotein receptor-related protein (LRP) plays a pivotal role in the trafficking of APP and generation of A,. In particular, we recently showed that the soluble cytoplasmic tail of LRP (LRP-ST) without a membrane tether was sufficient to promote A, generation. In this study, we demonstrate that the last 37 residues of LRP cytoplasmic tail (LRP-C37) lacking the NPxY motifs and FE65 binding mediate the core pro-amyloidogenic activity of LRP-ST. Moreover, we show that the conserved dileucine motif within the LRP-C37 region is a key determinant of its A, promoting activity. Finally, results from a yeast two-hybrid screen using LRP-C37 region as bait reveal four new LRP-binding proteins implicated in intracellular signalling and membrane protein trafficking. Our findings indicate that the LRP-C37 sequence represents a new protein-binding domain that may be useful as a therapeutic target and tool to lower A, generation in AD. [source] Association of low density lipoprotein receptor related protein-associated protein (LRPAP1) gene insertion/deletion polymorphism with gallstone diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2006MANJUSHA DIXIT Abstract Background and Aim:, Gallstones are byproducts of cholesterol supersaturated bile. Various studies have indicated that there might be a genetic predisposition to the disease. Receptor-associated protein (RAP) is a molecular chaperone for low density lipoprotein receptor-related protein (LRP), which plays a key role in cholesterol metabolism. Intron 5 insertion/deletion polymorphism of RAP gene (LRPAP1) has been implicated in other diseases sharing etiology with gallstone disease (GSD). Methods:, To analyze the association of insertion/deletion polymorphism in GSD, 130 gallstone patients and 202 healthy subjects took part in the present study. For genotyping, polymerase chain reaction was followed by 2% agarose gel electrophoresis. Results:, The results showed that frequencies of D and I allele were 65.77% and 34.23% in patients, 76.24% and 23.76% in controls, respectively. Frequency of I allele was significantly higher in the patient group than in the control group (P = 0.003). Conclusion:, In the present study I (insertion) allele was found to be associated with GSD. [source] Multidrug resistance in haematological malignanciesJOURNAL OF INTERNAL MEDICINE, Issue 5 2000P. Sonneveld Abstract. Sonneveld P (University Hospital Rotterdam , Dijkzigt, The Netherlands). Multidrug resistance in haematological malignancies (Internal Medicine in the 21st Century). J Intern Med 2000; 247: 521,534. The development of refractory disease in acute myeloid or lymphoblastic leukaemias (AML, ALL) and multiple myeloma (MM) is frequently associated with the expression of one or several multidrug resistance (MDR) genes. MDR1, MRP1 and LRP have been identified as important adverse prognostic factors in AML, T-ALL and MM. Recently, it has become possible to reverse clinical multidrug resistance by blocking P-glycoprotein-mediated drug efflux. The potential relevance of these reversal agents of MDR and potential new approaches to treat refractory disease are discussed. [source] High transcytosis of melanotransferrin (P97) across the blood,brain barrierJOURNAL OF NEUROCHEMISTRY, Issue 4 2002Michel Demeule Abstract The blood,brain barrier (BBB) performs a neuroprotective function by tightly controlling access to the brain; consequently it also impedes access of proteins as well as pharmacological agents to cerebral tissues. We demonstrate here that recombinant human melanotransferrin (P97) is highly accumulated into the mouse brain following intravenous injection and in situ brain perfusion. Moreover, P97 transcytosis across bovine brain capillary endothelial cell (BBCEC) monolayers is at least 14-fold higher than that of holo-transferrin, with no apparent intra-endothelial degradation. This high transcytosis of P97 was not related to changes in the BBCEC monolayer integrity. In addition, the transendothelial transport of P97 was sensitive to temperature and was both concentration- and conformation-dependent, suggesting that the transport of P97 is due to receptor-mediated endocytosis. In spite of the high degree of sequence identity between P97 and transferrin, a different receptor than the one for transferrin is involved in P97 transendothelial transport. A member of the low-density lipoprotein receptor protein family, likely LRP, seems to be involved in P97 transendothelial transport. The brain accumulation, high rate of P97 transcytosis and its very low level in the blood suggest that P97 could be advantageously employed as a new delivery system to target drugs directly to the brain. [source] The FE65 proteins and Alzheimer's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2008Declan M. McLoughlin Abstract The FE65s (FE65, FE65L1, and FE65L2) are a family of multidomain adaptor proteins that form multiprotein complexes with a range of functions. FE65 is brain-enriched, whereas FE65L1 and FE65L2 are more widely expressed. All three members contain a WW domain and two PTB domains. Through the PTB2 domain, they all interact with the Alzheimer's disease amyloid precursor protein (APP) intracellular domain (AICD) and can alter APP processing. After sequential proteolytic processing of membrane-bound APP and release of AICD to the cytoplasm, FE65 can translocate to the nucleus to participate in gene transcription events. This role is further mediated by interactions of FE65 PTB1 with the transcription factors CP2/LSF/LBP1 and Tip60 and the WW domain with the nucleosome assembly factor SET. However, FE65 target genes have not yet been confirmed. The FE65 PTB1 domain also interacts with two cell surface lipoproteins receptors, the low-density lipoprotein receptor-related protein (LRP) and ApoEr2, forming trimeric complexes with APP. The FE55 WW domain also binds to mena, through which it functions in regulation of the actin cytoskeleton, cell motility, and neuronal growth cone formation. While single knockout mice appear normal, double FE65,/,/FE65L1,/, mice have substantial neurodevelopmental defects. These include heterotopic neurons and axonal pathfinding defects, findings similar to findings in both Mena and triple APP:APLP1:APLP2 knockout mice and also lissencephalopathies in humans. Thus APPs, FE65s, and mena may act together in a developmental signalling pathway. This article reviews the known functions of the FE65 family and their role in APP function and Alzheimer's disease. © 2007 Wiley-Liss, Inc. [source] Integrated surface modification of fully polymeric microfluidic devices using living radical photopolymerization chemistryJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 4 2006Robert P. Sebra Abstract Surface modification using living radical polymerization (LRP) chemistry is a powerful technique for surface modification of polymeric substrates. This research demonstrates the ability to use LRP as a polymer substrate surface-modification platform for covalently grafting polymer chains in a spatially and temporally controlled fashion. Specifically, dithiocarbamate functionalities are introduced onto polymer surfaces using tetraethylthiuram disulfide. This technique enables integration of LRP-based grafting for the development of an integrated, covalent surface-modification method for microfluidic device construction. The unique photolithographic method enables construction of devices that are not substrate-limited. To demonstrate the utility of this approach, both controlled fluid flow and cell patterning applications were demonstrated upon modification with various chemical functionalities. Specifically, poly(ethylene glycol) (375) monoacrylate and trifluoroethyl acrylate were grafted to control fluidic flow on a microfluidic device. Before patterning, surface-functionalized samples were characterized with both goniometric and infrared spectroscopy to ensure that photografting was occurring through pendant dithiocarbamate functionalities. Near-infrared results demonstrated conversion of grafted monomers when dithiocarbamate-functionalized surfaces were used, as compared to dormant control surfaces. Furthermore, attenuated total reflectance/infrared spectroscopy results verified the presence of dithiocarbamate functionalities on the substrate surfaces, which were useful in grafting chains of various functionalities whose contact angles ranged from 7 to 86°. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1404,1413, 2006 [source] Low-density lipoprotein receptor-related protein (LRP)-mediated clearance of activated blood coagulation co-factors and proteases: clearance mechanism or regulation?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2006D. K. STRICKLAND No abstract is available for this article. [source] Synthesis and Evaluation of Water-Soluble Fluorinated Dendritic Block-Copolymer Nanoparticles as a 19F-MRI Contrast AgentMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 14 2010Michihiro Ogawa Abstract Well-defined water-soluble fluorinated polymer nanoparticles (PNPs) with a high fluorine content and biocompatibility were successfully prepared by living radical polymerization (LRP) of 2,2,3,3-tetrafluoropropyl methacrylate (TFPMA) from the polyamidoamine dendrimer macroinitiator (PAMAM-Br), and successive block polymerization of carboxybetaine monomer (CMB). The obtained core,shell type PNPs (PAMAM- g -PTFPMA- b -PCMB) showed high solubility in water and a sphere-like structure with a diameter in the range of 15,80,nm in water. The short 19F-NMR spin,lattice relaxation time (T1) (<250,ms) of PAMAM- g -PTFPMA- b -PCMB allowed the use of fast repetition time. The spin,spin relaxation time (T2) was evaluated to be as low as 10 ms. 19F-MRI in vitro signals can be detectable even at concentrations lower than 1 µM (particle concentration). These results demonstrate that a new type of 19F-MRI contrast agent can be developed by the molecular design using the dendrimer-initiated LRP method. [source] Fluorocarbon End-functionalized Polymers from Poly(arylether) Dendritic InitiatorsMACROMOLECULAR SYMPOSIA, Issue 1 2005A. Pillay Narrainen Abstract Fréchet-type poly(arylether) first and second generation (G1 and G2 respectively) dendrons were prepared from 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene. The latter and the brominated versions of the two dendrons were successfully employed in the copper mediated living radical polymerization (LRP) of styrene-d8 giving polymers of predictable molecular weights and narrow polydispersities. Contact angle measurements and ion beam analysis were used to explore the adsorption of these materials to the air-polymer surface in blended films with unfunctionalized hydrogenous polystyrene. Although contact angle analysis indicated only modest changes in the hydrophobicity and lipophobicity of the surface, ion beam analysis clearly showed the formation of an excess layer of dendron functionalized polymer at the exposed surface that increased with increasing fluorine content. [source] The Effect of Activation/Deactivation Processes on the Microcomposition and Microsequence Structure of Controlled/Living CopolymersMACROMOLECULAR THEORY AND SIMULATIONS, Issue 2-3 2008Ying Shi Abstract A new method is proposed to study the process of controlled/living radical copolymerization as well as the structures of the products. Computer simulation has been carried out to produce this LRP or CRP propagation including the activation/deactivation process. The information about segment distribution was obtained for the first time. The results show that under a stationary condition, controlled/living copolymer's composition and sequence distribution are totally identical to those prepared from the conventional free radical copolymerization (FRcP). In other words, the activation/deactivation process of controlled/living radical copolymerization has no effect on copolymer's microcomposition and microsequence structure. [source] Genetic,morphologic association study: association between the low density lipoprotein-receptor related protein (LRP) and cerebral amyloid angiopathyNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2005M. Christoforidis Accumulating evidence suggests that genetic factors such as apolipoprotein E (APOE), can act in different ways in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). The role of the low-density lipoprotein-receptor related protein (LRP), the major cerebral APOE receptor, in AD has been discussed controversially depending on data from different populations and methodological approaches. We examined the influence of LRP polymorphisms on CAA in 125 post-mortem cases genotyped for APOE and classified according to the neurofibrillary Braak and Braak staging of AD (indicating neurodegeneration grade). CAA was assessed separately for leptomeningeal (CAAlep.), noncapillary cortical (CAAcort.) and capillary cortical (CAAcap.) vessels in ,-amyloid stained sections. Our results suggest: (i) the 87 bp allele of LRP5, polymorphism (LRP5,) is an independent predictive factor for CAAcort. and CAAlep.; (ii) the C/C genotype (C allele) of the LRP exon 3 polymorphism is positively associated with, the, severity, of, CAAlep., and, CAAcort.,, implicating a younger age of CAA onset and/or faster CAA progression; (iii) as CAAcort. and CAAlep. showed different genetic associations in contrast to CAAcap., we can underscore the hypothesis that different molecular mechanisms are involved in CAA pathogenesis of noncapillary and capillary cerebral vessels. Our results lead us to postulate that the LRP5,87 bp and the LRP exon 3 C alleles of the LRP gene (or another locus that might be in linkage disequilibrium with these LRP polymorphic sites) could modify cerebrovascular LRP function or expression in noncapillary cerebral vessels, leading to an increased cerebrovascular amyloid deposition. [source] Cognitive processes facilitated by contextual cueing: Evidence from event-related brain potentialsPSYCHOPHYSIOLOGY, Issue 3 2009Andrea Schankin Abstract Finding a target in repeated search displays is faster than finding the same target in novel ones (contextual cueing). It is assumed that the visual context (the arrangement of the distracting objects) is used to guide attention efficiently to the target location. Alternatively, other factors, e.g., facilitation in early visual processing or in response selection, may play a role as well. In a contextual cueing experiment, participant's electrophysiological brain activity was recorded. Participants identified the target faster and more accurately in repeatedly presented displays. In this condition, the N2pc, a component reflecting the allocation of visual-spatial attention, was enhanced, indicating that attention was allocated more efficiently to those targets. However, also response-related processes, reflected by the LRP, were facilitated, indicating that guidance of attention cannot account for the entire contextual cueing benefit. [source] Task-dependent exogenous cuing effects depend on cue modalityPSYCHOPHYSIOLOGY, Issue 2 2006Robh.J. Van der Lubbe Abstract Task-dependent exogenous cuing effects on reaction time in detection and discrimination tasks have been ascribed to delayed withdrawal of attention in discrimination tasks. Alternatively, these differences may be due to cue-induced response inhibition in detection tasks. Unimodal and crossmodal versions of the Posner paradigm were examined with short cue,target intervals. Targets above or below fixation required either detection or discrimination responses. Cuing effects were determined for the target-elicited P1 component and for the lateralized readiness potential (LRP). Task-dependent cuing effects on reaction time were found in the unimodal but not in the crossmodal version, but not for the P1 component. The LRP data indicated that inhibition of return in the unimodal detection task had a premotoric locus. These findings suggest that inhibition in the unimodal detection task resulted from speeded motor inhibition triggered by the visual cue. [source] Locus of the effect of temporal preparation: Evidence from the lateralized readiness potentialPSYCHOPHYSIOLOGY, Issue 4 2003Hiltraut MÜller-Gethmann Abstract It is well established that reaction time (RT) is shorter when a response signal is preceded by a warning signal, because the warning signal causes the participant to prepare for the upcoming response. A review of chronometric and psychophysiological studies reveals the prevailing view that this temporal preparation operates mainly at a motor level speeding up rather late processes. To assess the locus of this preparation effect, we conducted two experiments employing the lateralized readiness potential (LRP). Contrary to this prevailing view, the results of both experiments clearly indicate that temporal preparation enhances the processing speed of relatively early processes, because a manipulation of temporal uncertainty affected RT, the P300 latency, and the stimulus-to-LRP interval but not the LRP-to-keypress interval. [source] Low-density lipoprotein receptor-related protein (LRP)-2/megalin is transiently expressed in a subpopulation of neural progenitors in the embryonic mouse spinal cordTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2005Grzegorz Wicher Abstract The lipoprotein receptor LRP2/megalin is expressed by absorptive epithelia and involved in receptor-mediated endocytosis of a wide range of ligands. Megalin is expressed in the neuroepithelium during central nervous system (CNS) development. Mice with homozygous deletions of the megalin gene show severe forebrain abnormalities. The possible role of megalin in the developing spinal cord, however, is unknown. Here we examined the spatial and temporal expression pattern of megalin in the embryonic mouse spinal cord using an antibody that specifically recognizes the cytoplasmic part of the megalin molecule. In line with published data, we show expression of megalin in ependymal cells of the central canal from embryonic day (E)11 until birth. In addition, from E11 until E15 a population of cells was found in the dorsal part of the developing spinal cord strongly immunoreactive against megalin. Double labeling showed that most of these cells express vimentin, a marker for immature astrocytes and radial glia, but not brain lipid binding protein (BLBP), a marker for radial glial cells, or glial fibrillary acidic protein (GFAP), a marker for mature astrocytes. These findings indicate that the majority of the megalin-positive cells are astroglial precursors. Megalin immunoreactivity was mainly localized in the nuclei of these cells, suggesting that the cytoplasmic part of the megalin molecule can be cleaved following ligand binding and translocated to the nucleus to act as a transcription factor or regulate other transcription factors. These findings suggest that megalin has a crucial role in the development of astrocytes of the spinal cord. J. Comp. Neurol. 492:123,131, 2005. © 2005 Wiley-Liss, Inc. [source] Erectile Function Recovery Rate after Radical Prostatectomy: A Meta-AnalysisTHE JOURNAL OF SEXUAL MEDICINE, Issue 9 2009Raanan Tal MD ABSTRACT Introduction., Erectile function recovery (EFR) rates after radical prostatectomy (RP) vary greatly based on a number of factors, such as erectile dysfunction (ED) definition, data acquisition means, time-point postsurgery, and population studied. Aim., To conduct a meta-analysis of carefully selected reports from the available literature to define the EFR rate post-RP. Main Outcome Measures., EFR rate after RP. Methods., An EMBASE and MEDLINE search was conducted for the time range 1985,2007. Articles were assessed blindly by strict inclusion criteria: report of EFR data post-RP, study population ,50 patients, ,1 year follow-up, nerve-sparing status declared, no presurgery ED, and no other prostate cancer therapy. Meta-analysis was conducted to determine the EFR rate and relative risks (RR) for dichotomous subgroups. Results., A total of 212 relevant studies were identified; only 22 (10%) met the inclusion criteria and were analyzed (9,965 RPs, EFR data: 4,983 subjects). Mean study population size: 226.5, standard deviation = 384.1 (range: 17,1,834). Overall EFR rate was 58%. Single center series publications (k = 19) reported a higher EFR rate compared with multicenter series publications (k = 3): 60% vs. 33%, RR = 1.82, P = 0.001. Studies reporting ,18-month follow-up (k = 10) reported higher EFR rate vs. studies with <18-month follow-up (k = 12), 60% vs. 56%, RR = 1.07, P = 0.02. Open RP (k = 16) and laparoscopic RP (k = 4) had similar EFR (57% vs. 58%), while robot-assisted RP resulted in a higher EFR rate (k = 2), 73% compared with these other approaches, P = 0.001. Patients <60 years old had a higher EFR rate vs. patients ,60 years, 77% vs. 61%, RR = 1.26, P = 0.001. Conclusions., These data indicate that most of the published literature does not meet strict criteria for reporting post-RP EFR. Single and multiple surgeon series have comparable EFR rates, but single center studies have a higher EFR. Younger men have higher EFR and no significant difference in EFR between ORP and LRP is evident. Tal R, Alphs HH, Krebs P, Nelson CJ, and Mulhall JP. Erectile function recovery rate after radical prostatectomy: A meta-analysis. J Sex Med 2009;6:2538,2546. [source] Local Influence Diagnostics for Quasi-Likelihood and Lognormal Estimates of a Biological Reference Point from Some Fish Stock and Recruitment ModelsBIOMETRICS, Issue 3 2006N. G. Cadigan Summary We present local influence diagnostics to measure the sensitivity of a biological limit reference point (LRP) estimated from fitting a model to stock and recruitment data. LRPs are low levels of stock size that the management of commercial fisheries should avoid with high probability. The LRP we examine is the stock size at which recruitment is 50% of the maximum (S50%). We derive analytic equations to describe the effects on S50% of changing the weight that observations are given in estimation. We derive equations for the Ricker, Beverton,Holt, and hockey-stick stock-recruit models, and four estimation methods including the error sums of squares method on log responses and three quasi-likelihood methods. We conclude from case studies that the hockey-stick model produces the most robust estimates. [source] Impact of ethnicity on surgical margins at radical prostatectomyBJU INTERNATIONAL, Issue 7 2009Farhang Rabbani OBJECTIVE To determine if the rate of positive surgical margins (PSMs), and in particular apical PSMs, at radical prostatectomy (RP) for prostate cancer, is higher in African-American (AA) than Caucasian men, given their often narrower and deeper pelvis. PATIENTS AND METHODS From 1999 to 2007, 3145 consecutive patients underwent RP, either open retropubic (RRP) or laparoscopic (LRP), with no previous treatment, by one of five surgeons. Multivariate logistic regression was used to determine the effect of ethnicity (AA vs Caucasian) on overall and site-specific PSMs, adjusting for age, body mass index, RP approach (RRP vs LRP), surgeon, surgeon case number, year of surgery, preoperative serum prostate-specific antigen level, specimen weight, estimated blood loss, pathological organ-confined status, and pathological Gleason score. RESULTS In all, 205 men were AA and 2940 Caucasian; PSMs were identified in 376 (12.0%) men, 35 (17.1%) in AA and 341 (11.6%) in Caucasian men. PSMs were identified at the apex in 148 (4.7%), the bladder neck in 29 (0.9%), posteriorly in 169 (5.4%), and anteriorly in 78 (2.5%) men. For apical PSM, ethnicity was a significant predictor, with an odds ratio of 1.76 (95% confidence interval 1.01,3.04, P = 0.045) for AA vs Caucasian, independent of pathological organ-confined status and PSA level. Ethnicity was not a significant independent predictor of overall PSMs or PSMs at other sites (bladder neck, posteriorly, or anteriorly). CONCLUSIONS The rate of apical PSMs, but not overall PSMs, at RP was higher in AA than Caucasian men, controlling for other covariates. Further investigation is necessary to determine if pelvic shape is responsible for this observation. [source] Laparoscopic inguinal hernia repair during laparoscopic radical prostatectomyBJU INTERNATIONAL, Issue 3 2007Benjamin C. Lee OBJECTIVE To describe our experience of simultaneous laparoscopic radical prostatectomy (LRP) and inguinal hernia repair (LIHR) with a non-absorbable mesh, as there are few reports of simultaneous herniorrhaphy during LRP. PATIENTS AND METHODS Forty patients who had simultaneous LIHR and LRP were retrospectively reviewed. All operations were completed via antegrade techniques using a non-absorbable mesh for the LIHR, as the results with absorbable mesh were disappointing. RESULTS In all, 48 clinically apparent hernias were repaired in 40 patients (mean age 60 years). Of these, 13 were left-sided, 23 right-sided, and six bilateral; 19 were direct, 14 indirect, two pantaloon, three femoral, and in 10 the type was not recorded. The mean operative duration was 172 min and the mean hospital stay was 1.5 days. Two patients had a urine leak after surgery, which resolved with no further intervention, and two developed a pelvic lymphocele, one at 4 months and the other at 2 months after surgery. Two patients required urinary catheter re-insertion for retention after surgical catheter removal at 9 and 10 days after surgery, respectively. One patient developed a deep venous thrombosis 19 days after surgery. Of the 40 patients, 36 (90%) were followed for a mean of 10 months; none had a hernia recurrence on the repaired side, while two developed a new symptomatic contralateral hernia. CONCLUSIONS LIHR is a successful and reliable way to treat symptomatic patients who are treated surgically for prostate cancer. [source] Clearance of coagulation factor VIII in very low-density lipoprotein receptor knockout miceBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2004Niels Bovenschen Summary Low-density lipoprotein receptor-related protein (LRP) contributes to factor VIII (FVIII) catabolism in vivo. Besides LRP, FVIII also interacts with very low-density lipoprotein receptor (VLDLR) in vitro. We investigated the physiological role of VLDLR in FVIII catabolism, using knockout mouse models for VLDLR and LRP, alone and in combination. VLDLR,/, mice displayed normal plasma FVIII, whereas VLDLR,/, LRP, double-knockout mice had slightly increased FVIII compared with LRP-deficient mice. Remarkably, VLDLR deficiency slightly accelerated FVIII clearance. Adenovirus-mediated overexpression of VLDLR did not lower plasma FVIII in LRP-deficient mice. We conclude that VLDLR does not act in concert with LRP in FVIII clearance in vivo. [source] Cancer and the blood,brain barrier: ,Trojan horses' for courses?BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008M Mazza The blood,brain barrier (BBB) limits the bioavailability of most bioactive molecules and drugs in the CNS, leaving clinicians with only a few options for pharmacotherapy. In this issue Regina et al. demonstrate that a ,Trojan horse' drug conjugate, acting as a substrate of a physiological BBB receptor that facilitates transcytosis, significantly improves drug transport into the CNS. Specifically, the low-density lipoprotein receptor-related protein (LRP) is used to carry a conjugate of paclitaxel and Angiopep-2, an aprotinin-derived peptide, across the BBB. Interestingly, in its conjugated form paclitaxel circumvents the efflux pumps at the BBB but still retains its activity against microtubules. Importantly, the authors were able to demonstrate improved therapeutic efficacy of this approach in orthotopic models of primary and metastatic brain cancer. This proof-of-principle study thus represents a milestone for drug delivery across the BBB but also a starting point for studies exploring wider applicability and potential limitations of the approach. British Journal of Pharmacology (2008) 155, 149,151; doi:fn1; published online 30 June 2008 [source] Copper-transporting P-Type Adenosine Triphosphatase (ATP7B) Is Expressed in Human Breast CarcinomaCANCER SCIENCE, Issue 1 2002Atsuko Kanzaki This is the first report to show that a copper-transporting P-type adenosine triphosphatase, ATP7B, is expressed in certain breast carcinomas, and a priori knowledge of its expression is important for the choice of therapy. We investigated the hypothesis that ATP7B, which was shown to be associated with cisplatin resistance in vitro, is expressed in certain breast carcinomas. To test this hypothesis, ATP7B expression and protein level were examined in 41 breast carcinomas using RT-PCR and immunohistochemistry. ATP7B gene/protein could be detected in 22.0% (9/41) of breast carcinomas and ATP7B gene expression was correlated well with the protein expression. In nine ATP7B-positive tumors, adjacent normal breast tissue was similarly analyzed, revealing that ATP7B is upregulated in breast carcinoma. ATP7B gene expression in poorly differentiated carcinoma was significantly higher than that in well-/moderately differentiated carcinoma (P=0.012). Furthermore, we found no association between the ATP7B gene/protein expression and that of MDR1, MRP1, LRP and BCRP. These findings suggested that ATP7B gene expression might be a chemoresistance marker for cisplatin in patients with poorly differentiated breast carcinoma. [source] Expression of Multidrug Resistance-related Transporters in Human Breast CarcinomaCANCER SCIENCE, Issue 4 2001Atsuko Kanzaki The expression levels of mRNA for multidrug resistance 1 (MDR1) gene, multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP), which confer multidrug resistance in vitro, were examined in 43 untreated breast carcinoma patients, of whom 38 subsequently received doxorubicin-based chemotherapy after surgery, in order to elucidate the roles of these genes in drug resistance in vivo. The mRNA levels were determined using a semi-quantitative reverse-transcription polymerase chain reaction method in breast carcinoma tissues including at least 80% carcinoma cells. The expression level of BCRP gene was low and did not vary markedly in comparison with that of MDR1, MRP1 or LRP gene. The expressions of MDR1 and MRP1 genes were correlated with each other, but the expression of BCRP or LRP gene did not correlate with that of other genes. These four gene expressions were independent of age, TNM categories and the status of progesterone or estrogen receptor. The expression levels of these four genes were not related to the relapse or prognosis of the 38 patients treated with doxorubicin-based chemotherapy. P-glycoprotein (P-gp)/MDRl, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma. [source] Expression of Drug Resistance-related Genes in Head and Neck Squamous Cell Carcinoma and Normal MucosaCANCER SCIENCE, Issue 1 2000Shitau Hirata We examined the expression levels of mRNA for multidrug resistance 1 (MDR1), multidrug resistance-associated protein (MRP), human canalicular multispecific organic anion transporter (cMOAT), lung resistance-related protein (LRP), topoisomerase II,, ,(Topo II,, ,) and topoisomerase I (Topo I) genes in human head and neck squamous cell carcinoma (HNSCC) specimens and mucosa (HNM) specimens, to elucidate their roles in relation to the biological characteristics and drug resistance in vivo. Fifty-eight samples (45 head and neck carcinomas and 13 head and neck mucosa) obtained during surgical resection or biopsy from 38 patients were analyzed using the quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. MDR1, MRP, LRP, Topo II,, Topo II,, and Topo I gene transcripts were detected in all the samples tested, but cMOAT mRNA was not detected in them. Comparisons of the expression levels in HNSCC with those in HNM showed that the Topo II, gene expression level was higher in HNSCC than in HNM (P=0.0298). Moreover, the Topo II, mRNA level was significantly higher in metastatic lymph node samples of HNSCC than in HNM samples (P=0.0205). There were no significant differences in the six genes' expression levels between samples exposed to platinum drugs and those not exposed to platinum drugs. These results suggest that it may be effective in anticancer therapy to use topoisomerase-targetting drugs against HNSCC, especially metastatic neck tumors, and that the expression of these genes in HNSCC is not associated with platinum drug exposure. [source] Atorvastatin increases expression of low-density lipoprotein receptor mRNA in human circulating mononuclear cellsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2010Anothai Pocathikorn Summary 1.,3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, or statins, are commonly used to lower plasma cholesterol levels. HMGCR and the low-density lipoprotein (LDL) receptor (LDLR) are of central importance to cholesterol homeostasis and yet there is a paucity of data on the effect of statins on the regulation of the LDLR and HMGCR in humans. 2.,In the present study, we examined the effect of atorvastatin on the expression of HMGCR, LDLR and LDLR-related protein (LRP) mRNA in circulating mononuclear cells. Twelve human volunteers were treated with atorvastatin, 20 mg/day for 4 weeks. 3.,Atorvastatin decreased plasma total and LDL,cholesterol by 29% (P < 0.0001) and 41% (P < 0.001), respectively, and increased LDLR mRNA abundance, in absolute terms, by 35% (P < 0.001) and 31% (P < 0.0001) and 37% (P = 0.01) relative to reference GAPDH and ,-actin mRNA, respectively. In contrast, atorvastatin had no significant effect on LRP or HMGCR mRNA levels. 4. The increase in LDLR mRNA in circulating mononuclear cells agrees with the few human studies conducted, as well as with in vitro and animal studies, whereas the unchanged HMGCR mRNA is consistent with the hepatic specificity of atorvastatin. The present study firmly documents an increase in LDLR mRNA levels in response to statin administration in normal humans. [source] | |||||||||||||||||||||||||||||||