Myocardial perfusion SPECT in Germany from 2012 to 2021: insights into development and quality indicators.

PURPOSE: This paper summarises the results of 4 national surveys on the numbers, utilisation and technique of myocardial perfusion SPECT (MPS) from 2012 to 2021. METHODS: A one-page questionnaire for information on MPS in 2012, 2015, 2018 and 2021 was sent to German centres practising nuclear medicine. To check for representativeness, the numbers obtained were related to official annual data and furthermore to the numbers of invasive coronary angiography procedures (ICA). RESULTS: MPS examinations increased by > 40% from 2012 to 2021 and showed a centralisation with increasing MPS per centre. In 2020, a mild impact of the COVID-19 pandemic could be observed in the form of only a slight MPS increase, which was compensated in the following year. Outpatient care cardiologists represent the most important referrer (70%). Mostly, 2-day protocols were used. One-day protocols and stress-only protocols showed insignificant changes. The use of exercise stress decreased steadily. In 2021, exercise stress was replaced by pharmacological stress as the most frequent stress modality. Camera systems showed a shift to more SPECT-CT systems. The use of gated SPECT increased to almost 90%. Quantitative scoring showed an increasing acceptance. The ratio of invasive coronary angiographies (ICA) to MPS was between 3.9 and 4.5. A significant proportion of ICA in the context of CCS (chronic coronary syndrome) was performed without prior testing for ischaemia. CONCLUSION: The 2012 to 2021 MPS surveys reveal a continuously growing number of examinations with only a mild temporary effect of the COVID-19 pandemic and a centralisation with increasing numbers per centre. Performance and technical data reveal a high-grade adherence of MPS practice to the current ESC guideline. A large potential of non-invasive diagnostics remains for the future.

[Primary treatment of flexor tendon injuries]. / Primärversorgung von Beugesehnenverletzungen.

The treatment of flexor tendon injuries is still challenging, especially in the region of the narrow annular ligaments and tendon sheaths of the 3­segment fingers and the thumb (zone 2). In the course of time, the primary suture of the flexor tendons has prevailed over traditional recommendations for a secondary tendon replacement after healing of the wound. Improvements regarding suture techniques and materials and, above all the follow-up treatment, have been crucial for better results and remarkable changes in flexor tendon surgery. The suture techniques are determined by the location of the injury but the experience and preferences of the surgeon are also important. Although no technique was found to be optimal, published research and clinical experiences provide important indications for the presumption of successful treatment. To achieve this an early functionally active protocol should be implemented. The tendon suture should enable this by having a high primary strength and therefore at least a 4-strand core suture technique with a ring suture should be given preference. Further important prerequisites for success are the undisturbed gliding of the repaired tendon in its "bed" paying special attention to the annular ligaments and preservation of the blood supply to the tendons.

The benefits of co-location in primary care practices: the perspectives of general practitioners and patients in 34 countries.

BACKGROUND: There is no clear evidence as to whether the co-location of primary care professionals in the same facility positively influences their way of working and the quality of healthcare as perceived by patients. The aim of this study was to identify the relationships between general practitioner (GP) co-location with other GPs and/or other professionals and the GP outcomes and patients' experiences. METHODS: We wanted to test whether GP co-location is related to a broader range of services provided, the use of clinical governance tools and inter-professional collaboration, and whether the patients of co-located GPs perceive a better quality of care in terms of accessibility, comprehensiveness and continuity of care with their GPs. The source of data was the QUALICOPC study (Quality and Costs of Primary Care in Europe), which involved surveys of GPs and their patients in 34 countries, mostly in Europe. In order to study the relationships between GP co-location and both GPs' outcomes and patients' experience, multilevel linear regression analysis was carried out. RESULTS: The GP questionnaire was filled in by 7183 GPs and the patient experience questionnaire by 61,931 patients. Being co-located with at least one other professional is the most common situation of the GPs involved in the study. Compared with single-handed GP practices, GP co-location are positively associated with the GP outcomes. Considering the patients' perspective, comprehensiveness of care has the strongest negative relationship of GP co-location of all the dimensions of patient experiences analysed. CONCLUSIONS: The paper highlights that GP mono- and multi-disciplinary co-location is related to positive outcomes at a GP level, such as a broader provision of technical procedures, increased collaboration among different providers and wider coordination with secondary care. However, GP co-location, particularly in a multidisciplinary setting, is related to less positive patient experiences, especially in countries with health systems characterised by a weak primary care structure.

Use of myocardial perfusion imaging and estimation of associated radiation doses in Germany from 2005 to 2012.

PURPOSE: For several years the Working Group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine has been performing a regular survey to obtain information on technique, utilization and development of myocardial perfusion scintigraphy (MPS). Currently, data of six surveys from 2005 to 2012 are available. The aim of this paper is to deliver a general and comprehensive overview of all surveys documenting the course of patient doses over time and the development of the method. METHODS: A one-page questionnaire with number of MPS patients, number of stress and rest MPS, referral structure and several technical issues was sent to all centres performing MPS in Germany and evaluated. With the data on protocol utilization, effective MPS patient doses were estimated. RESULTS: MPS per million population (pmp) varied between 2,380 and 2,770. In 2012, MPS pmp showed a slight increase for the first time. From 2005 to 2009 the angiography to MPS ratio increased from 3.4 to 4.4, and the revascularization to MPS ratio decreased from 0.66 to 0.53. In 2012, both indices demonstrated an opposite trend for the first time (4.1 and 0.55). A total of 108 centres participated in all surveys. They showed an increase in MPS patients of 4.0 % over the reporting period. In 2012, more than 50 % of the centres experienced no change or an increase in MPS numbers. The leading single competitor was MRI, followed by angiography and stress echocardiography. (201)Tl studies have decreased since 2005 from 20 to 5 %. (99m)Tc MPS studies showed a mild increase in 2-day protocols. In 2012, the average effective dose per patient was estimated at 7.4 mSv. Due to the decreasing use of (201)Tl, a mild decline over the observation period can be documented. Dynamic exercise stress was the most common stress test and adenosine the leading pharmacological stress agent, with a growing percentage. In 2012, the regadenoson percentage was 9 %. Gated single photon emission computed tomography (SPECT) noted an increasing acceptance with >70 % in 2012. The segmental scoring of perfusion studies had a low acceptance. Ambulatory care cardiologists represented the major referral group. CONCLUSION: Germany has a moderate to moderate-high MPS utilization rate. Nevertheless, coronary artery disease (CAD) diagnosis and disease management are dominated by angiography. The survey data reveal a positive trend in MPS and a decrease in average patient dose reflecting good practice with guideline adherence, the implementation of technical improvements and success in training.

[Psammomatous melanotic schwannoma as indicator of a Carney complex]. / Psammomatöses melanotisches Schwannom als Indikator eines Carney-Komplexes.

Within a few months a 31-year-old female patient was diagnosed with a psammomatous melanotic schwannoma, an atrial myxoma and microfollicular adenomas in both thyroid lobes. Therefore, sufficient diagnostic criteria of a Carney complex were fulfilled. The Carney complex is an inherited autosomal dominant disorder with highly variable phenotypes, which was initially described by Carney in 1985 as a complex of myxomas, spotty skin pigmentation and endocrine overactivity. Pathologists should consider this differential diagnosis in reports when confronted with a psammomatous melanotic schwannoma.

Automatic, three-segment, MR-based attenuation correction for whole-body PET/MR data.

PURPOSE: The combination of positron emission tomography (PET) and magnetic resonance (MR) tomography in a single device is anticipated to be the next step following PET/CT for future molecular imaging application. Compared to CT, the main advantages of MR are versatile soft tissue contrast and its capability to acquire functional information without ionizing radiation. However, MR is not capable of measuring a physical quantity that would allow a direct derivation of the attenuation values for high-energy photons. METHODS: To overcome this problem, we propose a fully automated approach that uses a dedicated T1-weighted MR sequence in combination with a customized image processing technique to derive attenuation maps for whole-body PET. The algorithm automatically identifies the outer contour of the body and the lungs using region-growing techniques in combination with an intensity analysis for automatic threshold estimation. No user interaction is required to generate the attenuation map. RESULTS: The accuracy of the proposed MR-based attenuation correction (AC) approach was evaluated in a clinical study using whole-body PET/CT and MR images of the same patients (n = 15). The segmentation of the body and lung contour (L-R directions) was evaluated via a four-point scale in comparison to the original MR image (mean values >3.8). PET images were reconstructed using elastically registered MR-based and CT-based (segmented and non-segmented) attenuation maps. The MR-based AC showed similar behaviour as CT-based AC and similar accuracy as offered by segmented CT-based AC. Standardized uptake value (SUV) comparisons with reference to CT-based AC using predefined attenuation coefficients showed the largest difference for bone lesions (mean value ± standard variation of SUV(max): -3.0% ± 3.9% for MR; -6.5% ± 4.1% for segmented CT). A blind comparison of PET images corrected with segmented MR-based, CT-based and segmented CT-based AC afforded identical lesion detectability, but slight differences in image quality were found. CONCLUSION: Our MR-based attenuation correction method offers similar correction accuracy as offered by segmented CT. According to the specialists involved in the blind study, these differences do not affect the diagnostic value of the PET images.

[Myocardial perfusion scintigraphy 2008 in Germany - results of the fourth query]. / Myokard-Perfusions-Szintigraphie 2008 in Deutschland - Ergebnisse der vierten Erhebung.

AIM: The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine in cooperation with the working group Nuclear Cardiology of the German Cardiac Society herewith present the results of the 4th survey on myocardial perfusion scintigraphy (MPS) of the year 2008. METHOD: 310 questionnaires (191 private practices (PP), 93 hospitals (HO), 31 university hospitals (UH)) were evaluated. RESULTS: MPS of 98947 patients were reported. 15% of them were younger than 50 y, 57% between 50 and 70 y and 28% older than 70 y. 88% [2007: 83%] of all were studied with Tc-99m perfusion tracers. The patient radiation exposure of a stress and rest protocol considering German standard recommended doses was 8.5 mSv, of a stress-only protocol 1.9 mSv. 77% [2007: 76%] of the MPS were performed in PP, 15% [2007: 15%] in HO and 8% [2007: 9%] in UH. From 2005 to 2008 there was a mild increase in the MPS numbers by 1.2% (PP +7.1%, HO -5.5%, UH -31.4%). The type of stress was pharmacological in 30% [2007: 27%]; 68% adenosine (of these 22% with exercise), 29% dipyridamole (of these 64% with exercise), and <1% dobutamine. Gated SPECT was performed in 46% [2007: 47%] of all rest and in 42% [2007: 44%] of all stress MPS. 62% [2007: 61%] of all institutions did not use perfusion scores. CONCLUSION: The MPS numbers from 2005 to 2008 in Germany can be regarded as stable. However, there are considerable shifts from HO and UH to PP. The well known potential of MPS considering risk stratification and functional analysis has not been tapped so far. Both gated SPECT and a quantitative perfusion analysis should be performed routinely in every patient.

[Use of synthetic slings and mesh implants in the treatment of female stress urinary incontinence and prolapse : Statement of the Working Group on Urological Functional Diagnostics and Female Urology of the Academy of the German Society of Urology]. / Einsatz von synthetischen Band- und Netzimplantaten bei der Behandlung von Belastungsinkontinenz und Descensus genitalis der Frau : Stellungnahme des Arbeitskreises Urologische Funktionsdiagnostik und Urologie der Frau der Akademie der Deutschen Gesellschaft für Urologie.

Due to a safety alert issued by the US Food and Drug Administration (FDA) in 2011 for transvaginal mesh implants to treat female prolapse as a result of numerous reports of complications such as infection, chronic pain, dyspareunia, vaginal erosion, shrinkage and erosion into other organs nearly all industrial products have been withdrawn from the market in the meantime. The United Kingdom, Australia, and New Zealand extended warnings and prohibitions even on the implantation of midurethral slings (TVT, TOT). In view of these current international controversies regarding the use of implanted materials for the treatment of stress incontinence and prolapse and the lack of clear guidelines for the use of biomaterials, the opinion of the Working Group on Urological Functional Diagnostics and Female Urology should provide clarity. The Opinion is based on the SCENIHR Report of the "European Commission's Scientific Committee on Emerging and Newly Identified Health Risks", the "Consensus Statement of the European Urology Association and the European Urogynaecological Association on the Use of Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence" and in compliance with relevant EAU and national guidelines and the opinion of the Association for Urogynaecology and Plastic Pelvic Floor Reconstruction (AGUB eV). In addition, recommendations are given for the future handling of implants of slings and meshes for the treatment of stress incontinence and prolapse from a urologic viewpoint.

Maturation of the trans-Golgi network protease furin: compartmentalization of propeptide removal, substrate cleavage, and COOH-terminal truncation.

We have cloned a bovine cDNA encoding the trans-Golgi network (TGN) protease furin and expressed it via recombinant vaccinia viruses to investigate intracellular maturation. Pulse-chase labeling reveals that the 104-kD pro-furin bearing high mannose N-glycans is rapidly processed into the 98-kD protease whose N-glycans remain sensitive to endoglycosidase H for a certain period of time. Furthermore, in the presence of brefeldin A, pro-furin cleavage occurs. From these data we conclude that the ER is the compartment of propeptide removal. Studies employing the ionophore A23187 and DTT show that autocatalysis is Ca2+ dependent and that it does not occur under reducing conditions. Pro-furin produced under these conditions never gains endo H resistance indicating that it is retained in the ER. Coexpression of furin with the fowl plague virus hemagglutinin in the presence of brefeldin A and monensin reveals that furin has to enter the Golgi region to gain substrate cleaving activity. N-glycans of furin are sialylated proving its transit through the trans-Golgi network. A truncated form of furin is found in supernatants of cells. Truncation is inhibited in the absence of Ca2+ ions and in the presence of acidotropic agents indicating that it takes place in an acidic compartment of cells. Comparative analysis with furin expressed from cDNA reveals that the truncated form prevails in preparations of biologically active, endogenous furin obtained from MDBK cells. This observation supports the concept that secretion of truncated furin is a physiological event that may have important implications for the processing of extracellular substrates.

Assembly of type C oncornaviruses: a model.

The salient features of this model for oncornavirus assembly are that uncleaved precursor molecules to the internal virus polypeptides possess specific recognition sites both for viral envelope constituents already inserted in the cell membrane and for the viral RNA. After orderly alignment of these components at the budding site, virus maturation proceeds through specific proteolytic cleavage of the precursor components and association of the resultant molecules into the characteristic type C virion substructures revealed by electron microscopy.

Common modifications of trimeric G proteins and ras protein: involvement of polyisoprenylation.

The heterotrimeric guanine nucleotide-binding regulatory proteins act at the inner surface of the plasma membrane to relay information from cell surface receptors to effectors inside the cell. These G proteins are not integral membrane proteins, yet are membrane associated. The processing and function of the gamma subunit of the yeast G protein involved in mating-pheromone signal transduction was found to be affected by the same mutations that block ras processing. The nature of these mutations implied that the gamma subunit was polyisoprenylated and that this modification was necessary for membrane association and biological activity. A microbial screen was developed for pharmacological agents that inhibit polyisoprenylation and that have potential application in cancer therapy.

One enzyme makes a fungal pathogen, but not a saprophyte, virulent on a new host plant.

Certain genes of Nectria haematococca, a fingal pathogen of pea (Pisum sativum), encode pisatin demethylase (pda), a cytochrome P-450 monoxygenase that detoxifies the phytoalexin pisatin. Because pda is required by N.haematococca for pathogenicity on pea, pisatin helps defend pea against N. haematococca. The possibility that pisatin is a general defense factormicrothat is, that pda can confer pathogenicity to fungi not normally pathogenic on peamicrowas investigated. Genes encoding pda were transformed into and highly expressed in Cochliobolus heterostrophus, a fungal pathogen of maize but not of pea, and in Aspergillus nidulans, a saprophytic fungus, neither of which produces a significant amount of pda. Transformants contained at least as much pda as did wild-type N. haematococca. Recombinant C. heterostrophus was normally virulent on maize, but it also caused symptoms on pea, whereas recombinant A. nidulans did not affect pea. Thus, phytoalexins can function in nonspecific resistance of plants to microbes; saprophytes appear to lack genes for basic pathogenicity.

Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans.

The activity of an oncoprotein and the secretion of a pheromone can be affected by an unusual protein modification. Specifically, posttranslational modification of yeast a-factor and Ras protein requires an intermediate of the cholesterol biosynthetic pathway. This modification is apparently essential for biological activity. Studies of yeast mutants blocked in sterol biosynthesis demonstrated that the membrane association and biological activation of the yeast Ras2 protein require mevalonate, a precursor of sterols and other isoprenes such as farnesyl pyrophosphate. Furthermore, drugs that inhibit mevalonate biosynthesis blocked the in vivo action of oncogenic derivatives of human Ras protein in the Xenopus oocyte assay. The same drugs and mutations also prevented the posttranslational processing and secretion of yeast a-factor, a peptide that is farnesylated. Thus, the mevalonate requirement for Ras activation may indicate that attachment of a mevalonate-derived (isoprenoid) moiety to Ras proteins is necessary for membrane association and biological function. These observations establish a connection between the cholesterol biosynthetic pathway and transformation by the ras oncogene and offer a novel pharmacological approach to investigating, and possibly controlling, ras-mediated malignant transformations.

Enzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein.

The post-translational processing of the yeast a-mating pheromone precursor, Ras proteins, nuclear lamins, and some subunits of trimeric G proteins requires a set of complex modifications at their carboxyl termini. This processing includes three steps: prenylation of a cysteine residue, proteolytic processing, and carboxymethylation. In the yeast Saccharomyces cerevisiae, the product of the DPR1-RAM1 gene participates in this type of processing. Through the use of an in vitro assay with peptide substrates modeled after a presumptive a-mating pheromone precursor, it was discovered that mutations in DPR1-RAM1 cause a defect in the prenylation reaction. It was further shown that DPR1-RAM1 encodes an essential and limiting component of a protein prenyltransferase. These studies also implied a fixed order of the three processing steps shared by prenylated proteins: prenylation, proteolysis, then carboxymethylation. Because the yeast protein prenyltransferase could also prenylate human H-ras p21 precursor, the human DPR1-RAM1 analogue may be a useful target for anticancer chemotherapy.

[Myocardial perfusion scintigraphy 2007 in Germany--results of the query and current status]. / Myokardperfusionsszintigraphie 2007 in Deutschland--Ergebnisse der Erhebung und Standortbestimmung.

AIM: This third survey of the working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine in cooperation with the working group Nuclear Cardiology of the German Cardiac Society was to deliver information on the procedures and in particular on the development of myocardial perfusion scintigraphy (MPS) from 2005 to 2007. METHOD: 370 questionnaires (222 private practices (PP), 117 hospitals (HO), 31 university hospitals (UH)) were evaluated. RESULTS: MPS of 114,374 patients were reported, 83% were investigated with 99mTc-perfusion tracers. 76% [2006=74%] were performed in PP, 15% [2006=17%] in HO and 9% [2006=9%] in UH. Diabetics represented 21% of all MPS patients in 2007. Data of 215 institutions which participated all from 2005 to 2007 showed an increase in MPS of 2.3% (PP +6.8%, HO -4.5%, UH -18.2%). The type of stress was pharmacological in 27% [2006 = 27%]; 67% adenosine (of these 25% with exercise), 31% dipyridamole (of these 55% with exercise), and 2% dobutamine. Gated SPECT was performed in 47% [2006 = 42%] of all rest and in 44% [2006 = 39%] of all stress MPS. 61% [2006 = 83%] of all institutions did not apply perfusion scores. 20% [2006 = 24%] of the institutions reported changes in the use of MPS by competing methods. CONCLUSION: There is a small increase of MPS between 2005 and 2007 despite competing methods. Gated SPECT has experienced more acceptance, but is still underrepresented. As compared to the European average and general standards of MPS a considerable backlog accounts to pharmacological stress tests, gated SPECT and perfusion scores.

Control of alternative behavioral states by serotonin in Caenorhabditis elegans.

Serotonin has been implicated in the regulation of a wide range of brain functions involving alternative behavioral states, including the control of mood, aggression, sex, and sleep. Here, we report that in the nematode Caenorhabditis elegans, serotonin controls a switch between two distinct, on/off states of egg-laying behavior. Through quantitative analysis of the temporal pattern of egg-laying events, we determined that egg laying can be modeled as a novel random process, in which animals fluctuate between discrete behavioral states: an active state, during which eggs are laid in clusters, and an inactive state, during which eggs are retained. Single-cell ablation experiments indicate that two pairs of motor neurons, HSNL/HSNR and VC4/VC5, can induce the active phase by releasing serotonin. These neurons also release acetylcholine, which appears to trigger individual egg-laying events within the active phase. Genetic experiments suggest that determination of the behavioral states observed for C. elegans egg laying may be mediated through protein kinase C-dependent (PKC-dependent) modulation of voltage-gated calcium channels.

Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans.

Electrophysiology and optical indicators have been used in vertebrate systems to investigate excitable cell firing and calcium transients, but both techniques have been difficult to apply in organisms with powerful reverse genetics. To overcome this limitation, we expressed cameleon proteins, genetically encoded calcium indicators, in the pharyngeal muscle of the nematode worm Caenorhabditis elegans. In intact transgenic animals expressing cameleons, fluorescence ratio changes accompanied muscular contraction, verifying detection of calcium transients. By comparing the magnitude and duration of calcium influx in wild-type and mutant animals, we were able to determine the effects of calcium channel proteins on pharyngeal calcium transients. We also successfully used cameleons to detect electrically evoked calcium transients in individual C. elegans neurons. This technique therefore should have broad applications in analyzing the regulation of excitable cell activity in genetically tractable organisms.

[Myocardial perfusion scintigraphy 2006 in Germany. Results of the query and current status]. / Myokardperfusionsszintigraphie 2006 in Deutschland Ergebnisse der Erhebung und Standortbestimmung.

AIM: This second survey was to deliver further information on myocardial perfusion scintigraphy (MPS) in Germany in 2006. METHOD: 351 questionnaires were evaluated: 207 private practices (PP), 117 hospitals (HO), 27 from university hospitals (UH). RESULTS: MPS of 106 331 patients were reported, 85% were investigated with (99m)Tc-perfusion tracers. 74% [2005 = 72%] were performed in PP, 17% [2005 = 15%] in HO and 9% [2005 = 13%] in UH. PP, which participated in 2005 and 2006, demonstrated an increase by 3,9% (HO 0%, UH - 13,0%). The type of stress was pharmacological in 27% [2005 = 22%]; 54% adenosine (of these 29% with exercise), 37% dipyridamole (of these 56% with exercise), and 9% dobutamine. Gated SPECT was performed in 42% [2005 = 36%] of all rest- and in 39% [2005 = 32%] of all stress MPS. An attenuation correction was used by 69 [2005 = 78] institutions. 40% of all MPS were performed in patients suspected to have CAD. 24% of all institutions reported changes in the use of MPS by competing methods. CONCLUSION: There is a small increase of MPS between 2005 and 2006 despite competing methods. Gated SPECT has experienced more acceptance. Suspicion of CAD is an important indication of MPS. In order to tap the full potential of MPS a gated SPECT should be performed routinely.

Positive and negative transcriptional control by heme of genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae.

Responses of the yeast genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, HMG1 and HMG2, to in vivo changes in heme concentrations were investigated. Expression of the genes was determined by direct measurement of the mRNA transcribed from each gene, by direct assay of the enzyme activity encoded by each gene, and by measurement of the expression of lacZ fusions to the control regions of each gene. These studies indicated that expression of HMG1 was stimulated by heme, whereas expression of HMG2 was repressed by heme. The effect of heme on HMG1 expression was mediated by the HAP1 transcriptional regulator and was independent of HAP2. Thus, the genes encoding the 3-hydroxy-3-methylglutaryl coenzyme A reductase isozymes join a growing list of gene pairs that are regulated by heme in opposite ways.

Ran-binding protein 5 (RanBP5) is related to the nuclear transport factor importin-beta but interacts differently with RanBP1.

We report the identification and characterization of a novel 124-kDa Ran binding protein, RanBP5. This protein is related to importin-beta, the key mediator of nuclear localization signal (NLS)-dependent nuclear transport. RanBP5 was identified by two independent methods: it was isolated from HeLa cells by using its interaction with RanGTP in an overlay assay to monitor enrichment, and it was also found by the yeast two-hybrid selection method with RanBP1 as bait. RanBP5 binds to RanBP1 as part of a trimeric RanBP1-Ran-RanBP5 complex. Like importin-beta, RanBP5 strongly binds the GTP-bound form of Ran, stabilizing it against both intrinsic and RanGAP1-induced GTP hydrolysis and also against nucleotide exchange. The GAP resistance of the RanBP5-RanGTP complex can be relieved by RanBP1, which might reflect an in vivo role for RanBP1. RanBP5 is a predominantly cytoplasmic protein that can bind to nuclear pore complexes. We propose that RanBP5 is a mediator of a nucleocytoplasmic transport pathway that is distinct from the importin-alpha-dependent import of proteins with a classical NLS.