Publications by authors named "Andreas Schroeder"

30 Publications

  • Page 1 of 1

Avelumab and cetuximab as a therapeutic combination: An overview of scientific rationale and current clinical trials in cancer.

Cancer Treat Rev 2021 Jun 2;97:102172. Epub 2021 Mar 2.

Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

Treatment outcomes have improved with the advent of immune checkpoint inhibitors and small molecule inhibitors. However, many patients do not respond with single agents. Consequently, ongoing research is focused on the use of combination therapies to increase clinical efficacy by potential synergistic effects. Here, we outline ongoing trials and review the rationale and evidence for the combination of avelumab, an anti-programmed death ligand 1 (PD-L1) immunoglobulin G1 (IgG1) monoclonal antibody (mAb), with cetuximab, an anti-epidermal growth factor receptor (EGFR) IgG1 mAb. Avelumab is approved as a monotherapy for the treatment of Merkel cell carcinoma and urothelial carcinoma, and in combination with axitinib for renal cell carcinoma; cetuximab is approved in combination with chemotherapy for the treatment of squamous cell carcinoma of the head and neck (SCCHN) and RAS wild-type metastatic colorectal cancer, and in combination with radiation therapy for SCCHN. Avelumab binds to PD-L1 expressed on tumor cells and immune regulatory cells, thus blocking its interaction with programmed death 1 and reventing T-cell suppression; cetuximab inhibits the EGFR signaling pathway, inhibiting proliferation and inducing apoptosis. Both therapies have complementary mechanisms of action and may also activate the immune system to induce innate effector function through the binding of their Fc regions to natural killer (NK) cells. Furthermore, cetuximab combined with chemotherapy has been shown to induce immunogenic cell death and leads to an increase in tumor-infiltrating CD8+ T and NK cells, which should synergize with the immunostimulatory effects of avelumab. Prospective studies will investigate this combination and inform future treatment strategies.
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http://dx.doi.org/10.1016/j.ctrv.2021.102172DOI Listing
June 2021

Surface conditioning of additively manufactured titanium implants and its influence on materials properties and in vitro biocompatibility.

Mater Sci Eng C Mater Biol Appl 2021 Feb 15;119:111631. Epub 2020 Oct 15.

Carl Gustav Carus University Medical Center, Department of Orthodontics, TU Dresden, Dresden, Germany.

Customized osteosynthesis materials of titanium alloy can be generated by additive manufacturing replacing the complex adaptation to the patient individual anatomy, especially to the lower jaw bone which shows a highly individual surface area. After printing further conditioning is necessary to adjust surface roughness. The aim of the present study was to analyse the effect of different grinding and polishing procedures on sample surface and composition and in vitro biocompatibility. Ti-6Al-4V ELI samples printed by laser powder bed fusion (LPBF) were post-treated by multi-level procedures to adjust surface roughness using the surface conditioning technologies sandblasting, vibratory finishing, electro polishing or plasma polishing. Topography and chemical composition of the surfaces was analysed. Furthermore, the release of metal ions in contact to cell culture medium was quantified. Human osteoblasts as well as primary human gingiva cells (fibroblasts and epithelial cells) were cultivated in extracts or directly on the surfaces to analyse cytotoxicity, cell adhesion and cell proliferation. Surface roughness of the different materials after final polishing was in between 0.2 and 0.5 μm, which is in the same range as usually found for conventional titanium materials used in maxillofacial surgery. Furthermore, the wettability was comparable for all post-processing techniques. The chemical compositions of the finished surfaces showed a remarkable impact by the applied finishing technique. Extracts of the samples showed low cytotoxicity with exception of the plasma polished samples, which were shown to release significantly higher amounts of vanadium ions. Accordingly, cells showed good adhesion and proliferation on all samples except plasma polished specimens. Customized devices for midline osseodistraction were exemplarily printed with LPBF starting with patient's 3D data. Those devices can be considered for clinical use, since the printed and finished material meets the requirements of ISO 10993-5 for medical devices.
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http://dx.doi.org/10.1016/j.msec.2020.111631DOI Listing
February 2021

Estado nutricional de niños y niñas con parálisis cerebral que asisten a centros de rehabilitación.

Dev Med Child Neurol 2020 Oct 5. Epub 2020 Oct 5.

Instituto de Investigación en Ciencias de la Salud, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Cordoba, Argentina.

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http://dx.doi.org/10.1111/dmcn.14680DOI Listing
October 2020

Ultracold Electrons via Near-Threshold Photoemission from Single-Crystal Cu(100).

Phys Rev Lett 2020 Jul;125(5):054801

Lawrence Berkeley National Lab, Berkeley, California 94720, USA.

Achieving a low mean transverse energy or temperature of electrons emitted from the photocathode-based electron sources is critical to the development of next-generation and compact x-ray free electron lasers and ultrafast electron diffraction, spectroscopy, and microscopy experiments. In this Letter, we demonstrate a record low mean transverse energy of 5 meV from the cryo-cooled (100) surface of copper using near-threshold photoemission. Further, we also show that the electron energy spread obtained from such a surface is less than 11.5 meV, making it the smallest energy spread electron source known to date: more than an order of magnitude smaller than any existing photoemission, field emission, or thermionic emission based electron source. Our measurements also shed light on the physics of electron emission and show how the energy spread at few meV scale energies is limited by both the temperature and the vacuum density of states.
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http://dx.doi.org/10.1103/PhysRevLett.125.054801DOI Listing
July 2020

Childhood Arterial Ischaemic Stroke: Clinical Presentation, Risk Factors and Management.

Hamostaseologie 2020 Jun 23;40(2):165-173. Epub 2020 Apr 23.

Division of Paediatric Neurology and Developmental Medicine, Department of Paediatrics, LMU Munich, University Hospital, Dr. von Hauner Children's Hospital, Munich, Germany.

Childhood arterial ischaemic stroke (AIS) is a rare, but potentially life-threatening event which requires early diagnosis and adequate treatment. The reported significant time delay to childhood AIS diagnosis may be associated with low awareness, the more nonspecific clinical presentation as well as difficult clinical differentiation to more common "stroke mimics" and a less established "acute care structure" with delayed access to proper neuroimaging. Compared with adult stroke care, experiences with acute reperfusion therapies like thrombolysis and mechanical thrombectomy are promising but limited and not based on clinical trials. The etiological work-up is absolutely essential, as the child's individual risk profile determines acute management, secondary prevention, risk of recurrence and outcome. Follow-up care should be organized in a multidisciplinary setting covering all bio-psycho-social aspects to achieve the best integration of the child into its educational, later professional and social environments.
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http://dx.doi.org/10.1055/a-1113-0445DOI Listing
June 2020

Exposure and cognitive-behavioural therapy for chronic back pain: An RCT on treatment processes.

Eur J Pain 2019 03 4;23(3):526-538. Epub 2018 Nov 4.

Department of Clinical Psychology and Psychotherapy, Philipps-University Marburg, Marburg, Germany.

Background: To improve treatment outcomes, it is essential to understand the processes involved in therapeutic change. The aim of this study was to investigate the processes involved in treatment of individuals with chronic lower back pain (CLBP) and high fear-avoidance. Graded in vivo exposure (Exposure), a specific treatment, and cognitive-behavioural therapy (CBT), a general treatment, were compared.

Methods: Our study used data from a three-arm randomized controlled trial. The sample comprised 61 CLBP patients (pain duration >3 months; sufficient level of fear-avoidance). Assessments of session-by-session processes were done weekly for a maximum 14 weeks. The primary outcome, functional disability, was assessed at pre-treatment, post-treatment and 6-months follow-up. First, two-level models were used to test for treatment-related similarities and differences in the changes in session-by-session measures (i.e., common and unique treatment processes respectively). Second, we analysed treatment processes as predictors of treatment outcome.

Results: Contrary to our expectations, we found no evidence of unique treatment processes. Our results indicate that Exposure and CBT share some treatment processes. Specifically, patients reported a reduction in fear of movement and improvements in their ability to relax, to distract themselves, to manage their pain, to confront feared movements, to be active and to enjoy things despite their pain. Changes in fear of movement, relaxation, distraction, confrontation, activity and pain-related self-efficacy were also related to disability reduction.

Conclusions: Despite conceptual differences, Exposure and CBT may share common treatment processes. Future research needs to address, however, whether these processes need to be targeted directly or can be supported indirectly.

Significance: We identified several treatment processes (e.g., reduction of fear of movement, enhancement of self-efficacy), which were associated with disability reduction during the management of chronic pain and fear-avoidance. These processes appeared to be equally important for Exposure and CBT. Practitioners should optimize these processes to improve their patients' functioning.
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http://dx.doi.org/10.1002/ejp.1326DOI Listing
March 2019

Successful mechanical thrombectomy in a three-year-old boy with cardioembolic occlusion of both the basilar artery and the left middle cerebral artery.

Eur J Paediatr Neurol 2016 Nov 25;20(6):962-965. Epub 2016 Jul 25.

Department of Neuroradiology, Ludwig-Maximilians-University of Munich, Marchioninistr.15, 81377 Munich, Germany.

Background: Paediatric stroke is a potentially life-threatening emergency and requires immediate treatment to improve clinical outcome. In contrast to adult treatment recommendations, little is known about safety and efficacy of thrombolysis and mechanical thrombectomy in children.

Case Description And Conclusion: We report on a three-year-old boy with a cardioembolic intracranial two-vessel occlusion and successful therapy with thrombolysis and mechanical thrombectomy. Furthermore, this case emphasizes the need of standardized protocols for acute management of paediatric stroke.
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http://dx.doi.org/10.1016/j.ejpn.2016.07.014DOI Listing
November 2016

Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

Sci Rep 2016 Jan 5;6:18725. Epub 2016 Jan 5.

Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905.

Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.
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http://dx.doi.org/10.1038/srep18725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700525PMC
January 2016

Index of contrast sensitivity (ICS) in pseudophakic eyes with different intraocular lens designs.

Acta Ophthalmol 2015 May 27;93(3):e181-7. Epub 2014 Aug 27.

Institute of Experimental Ophthalmology, Saarland University, Homburg (Saar), Germany.

Purpose: To evaluate the index of contrast sensitivity (ICS) in eyes after cataract surgery with various intraocular lens designs and to compare with the area under log contrast sensitivity curve (AULCSF).

Methods: The study comprised 395 eyes of 198 patients in the age of 73.1 ± 7.86 years receiving 11 different aspheric IOL designs (aberration-free and correcting) and a spherical (IOL) as control group. Follow-up examination after bilateral cataract surgery was completed within 71 ± 21.4 days after second IOL implantation. Patients underwent complete examination and biometry before surgery. The follow-up examination included visual acuity, pupil diameter, residual spherical aberration and mesopic as well as photopic contrast sensitivity (CS) measured with the Optec 6500 Functional Vision Analyzer. From the contrast sensitivity, we calculated the ICS according to Haughom and Strand.

Results: The median mesopic ICS was -144, -131 and -85, and the median photopic ICS was -289, -285 and -212 for the spherical, aberration-free and aberration-correcting IOL group, respectively. While we could not detect a significant difference between the aberration groups in some spatial frequencies, the ICS showed a significant difference between the aberration-correcting and the aberration-free or the spherical group, respectively. No significant difference was found between the aberration-free and the spherical group.

Conclusions: The ICS is a useful index for evaluation of overall CS and comparison of different patient groups. With aberration-correcting IOLs, ICS was statistically better than with aberration-free or spherical IOLs, whereas the latter two showed no significant difference.
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http://dx.doi.org/10.1111/aos.12538DOI Listing
May 2015

Patient-specific determinants of responsiveness to robot-enhanced treadmill therapy in children and adolescents with cerebral palsy.

Dev Med Child Neurol 2014 12 25;56(12):1172-1179. Epub 2014 Aug 25.

Department of Pediatric Neurology and Developmental Medicine, Hauner Children's Hospital, University of Munich, Munich, Germany.

Aim: The aim of the study was to evaluate patient-specific determinants of responsiveness to robot-enhanced repetitive treadmill therapy (ROBERT) in patients with early-developed movement disorders.

Method: Patients were treated over 12 sessions during a 3-week period. Gross Motor Function Measure-66 (GMFM-66) scores 1 day before ROBERT were compared with scores recorded 1 day after ROBERT. The association of GMFM-66 baseline score, age, sex, aetiology, and add-on botulinum toxin therapy to response to treatment was assessed.

Results: Eighty-three patients aged between 4 and 18 years (48 males, 35 females; mean age 10y 8mo, SD 6y 1mo; Gross Motor Function Classification System level I [n=12], II [n=21], III [n=35], IV [n=10], and V [n=1]) were each treated for a total of 7.2 (SD 1.9) treadmill walking hours. Aetiology was bilateral spastic cerebral palsy (BS-CP; n=69), unilateral CP (n=3), ataxic CP (n=3), hereditary spastic paraparesis (n=6), and genetic syndrome including spasticity (n=2). Meaningful improvements were observed in GMFM-66 (+2.5; 95% CI 2.0-3.0), GMFM-D (+5.2; 95% CI 3.6-6.8), and GMFM-E (+4.0; 95% CI 2.8-5.3). There was a high inter-individual variability in treatment response. After multivariable adjustment, the improvements in GMFM-66 and GMFM-E scores were positively associated with the GMFM-66 baseline score. The effect on GMFM-D improvement was inversely associated with age.

Interpretation: Gross motor abilities at baseline and age were identified as relevant determinants for the high degree of interpersonal variability in response to ROBERT.
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http://dx.doi.org/10.1111/dmcn.12564DOI Listing
December 2014

Self-reported neck pain is associated with migraine but not with tension-type headache in adolescents.

Cephalalgia 2014 Oct 19;34(11):895-903. Epub 2014 Feb 19.

Institute of Social Paediatrics and Adolescent Medicine, LMU Munich, Germany.

Aim: The aim of the present analysis is to confirm or refute the association of neck pain to migraine or tension-type headache and to assess whether this association is independent of other risk factors for headache.

Methods: Secondary school students were invited to complete a questionnaire on headache and lifestyle factors in a cross-sectional study. Neck pain was assessed via (a) a screening question concerning neck pain and (b) denoting affected areas in schematic drawings of the human body.

Results: Absolute increment in prevalence of headache with pain in the shoulder-neck region was between 7.5% and 9.6%. Gender, grade, stress and lifestyle factors were assessed as potential confounding factors. Nearly all factors were associated with shoulder-neck pain and most with headache. After adjustment for confounders, the association of neck pain with headache was almost completely confined to migraine (OR 2.39; 95% CI 1.48-3.85) and migraine + tension-type headache (OR 2.12; 95% CI 1.50-2.99), whereas the association with isolated tension-type headache was negligible (OR 1.22, 95% CI 0.87-1.69).

Conclusion: Neck pain is associated with migraine but not with tension-type headache. A possible link between migraine and neck pain may be the cervico-trigeminal convergence of neck and meningeal sensory afferents or a disturbed descending inhibition in migraine.
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http://dx.doi.org/10.1177/0333102414523338DOI Listing
October 2014

Reduced GM1 ganglioside in CFTR-deficient human airway cells results in decreased β1-integrin signaling and delayed wound repair.

Am J Physiol Cell Physiol 2014 May 5;306(9):C819-30. Epub 2014 Feb 5.

Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Mayo Clinic and Foundation, Rochester, Minnesota;

Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function reduces chloride secretion and increases sodium uptake, but it is not clear why CFTR mutation also results in progressive lung inflammation and infection. We previously demonstrated that CFTR-silenced airway cells migrate more slowly during wound repair than CFTR-expressing controls. In addition, CFTR-deficient cells and mouse models have been reported to have altered sphingolipid levels. Here, we investigated the hypothesis that reduced migration in CFTR-deficient airway epithelial cells results from altered sphingolipid composition. We used cell lines derived from a human airway epithelial cell line (Calu-3) stably transfected with CFTR short hairpin RNA (CFTR-silenced) or nontargeting short hairpin RNA (controls). Cell migration was measured by electric cell substrate impedance sensing (ECIS). Lipid analyses, addition of exogenous glycosphingolipids, and immunoblotting were performed. We found that levels of the glycosphingolipid, GM1 ganglioside, were ~60% lower in CFTR-silenced cells than in controls. CFTR-silenced cells exhibited reduced levels of activated β1-integrin, phosphorylated tyrosine 576 of focal adhesion kinase (pFAK), and phosphorylation of Crk-associated substrate (pCAS). Addition of GM1 (but not GM3) ganglioside to CFTR-silenced cells restored activated β1-integrin, pFAK, and pCAS to near control levels and partially restored (~40%) cell migration. Our results suggest that decreased GM1 in CFTR-silenced cells depresses β1-integrin signaling, which contributes to the delayed wound repair observed in these cells. These findings have implications for the pathology of cystic fibrosis, where altered sphingolipid levels in airway epithelial cells could result in a diminished capacity for wound repair after injury.
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http://dx.doi.org/10.1152/ajpcell.00168.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010808PMC
May 2014

Intrinsic electron beam emittance from metal photocathodes: the effect of the electron effective mass.

Phys Rev Lett 2013 Dec 4;111(23):237401. Epub 2013 Dec 4.

Department of Physics, University of Illinois at Chicago, 845 W. Taylor Street, Chicago, Illinois 60607-7059, USA.

A theoretical development of prior analyses, together with our solenoid scan measurements on eight planar metal photocathodes (Ag, Be, Cr, Cu, Mo, Sn, Ta, and W) and previous data on Mg [X. J. Wang, M. Babzien, R. Malone, and Z. Wu, in Proceedings of LINAC2002, Gyeongju, Korea, 2002 (Pohang Accelerator Laboratory, Pohang, Korea, 2002), pp. 142-144.] indicate that the transverse momentum (and hence intrinsic emittance) of an electron beam is fundamentally dependent on the electron effective mass in the metal.
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http://dx.doi.org/10.1103/PhysRevLett.111.237401DOI Listing
December 2013

Early infantile sensory-motor neuropathy with late onset respiratory distress.

Neuromuscul Disord 2014 Mar 1;24(3):269-71. Epub 2013 Dec 1.

Department of Paediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Germany.

Children with spinal muscular atrophy with respiratory distress (SMARD1) usually present within their first year of life, with respiratory failure due to diaphragmatic paralysis and progressive distal limb weakness. We present a child with a confirmed compound heterozygous IGHMBP2 mutation c.[676G>T];[2083A>T] in whom severe sensory-motor neuropathy preceded diaphragmatic paralysis by almost 3years. Autonomic system involvement with neurogenic bladder and urine retention were found at 3years. In summary, our patient highlights the broad spectrum of phenotypes observed in SMARD1. Currently, no prediction of phenotype according to genotype is possible, suggesting that yet unknown factors cause the observed phenotypic variation. Even in the absence of obvious diaphragmatic weakness, SMARD1 should be considered in severe infantile onset neuropathies. High throughput techniques, such as next generation sequencing, will possibly offer a useful approach in the heterogeneous group of inherited neuropathies.
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http://dx.doi.org/10.1016/j.nmd.2013.11.013DOI Listing
March 2014

Relief of autoinhibition enhances Vta1 activation of Vps4 via the Vps4 stimulatory element.

J Biol Chem 2013 Sep 23;288(36):26147-26156. Epub 2013 Jul 23.

From the Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.

The endosomal sorting complexes required for transport (ESCRTs) impact multiple cellular processes including multivesicular body sorting, abscission, and viral budding. The AAA-ATPase Vps4 is required for ESCRT function, and its full activity is dependent upon the co-factor Vta1. The Vta1 carboxyl-terminal Vta1 SBP1 Lip5 (VSL) domain stimulates Vps4 function by facilitating oligomerization of Vps4 into its active state. Here we report the identification of the Vps4 stimulatory element (VSE) within Vta1 that is required for additional stimulation of Vps4 activity in vitro and in vivo. VSE activity is autoinhibited in a manner dependent upon the unstructured linker region joining the amino-terminal microtubule interacting and trafficking domains and the carboxyl-terminal VSL domain. The VSE is also required for Vta1-mediated Vps4 stimulation by ESCRT-III subunits Vps60 and Did2. These results suggest that ESCRT-III binding to the Vta1 microtubule interacting and trafficking domains relieves linker region autoinhibition of the VSE to produce maximal activation of Vps4 during ESCRT function.
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http://dx.doi.org/10.1074/jbc.M113.494112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764817PMC
September 2013

Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis.

Biochem Biophys Res Commun 2013 May 10;434(3):466-72. Epub 2013 Apr 10.

Departments of Medicine, Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Background: Membrane protrusions play important roles in biological processes such as cell adhesion, wound healing, migration, and sensing of the external environment. Cell protrusions are a subtype of membrane microdomains composed of cholesterol and sphingolipids, and can be disrupted by cholesterol depletion. Prominins are pentaspan membrane proteins that bind cholesterol and localize to plasma membrane (PM) protrusions. Prominin-1 is of great interest as a marker for stem and cancer cells, while Prominin-2 (Prom2) is reportedly restricted to epithelial cells.

Aim: To characterize the effects of Prom-2 expression on PM microdomain organization.

Methods: Prom2-fluorescent protein was transfected in human skin fibroblasts (HSF) and Chinese hamster ovary (CHO) cells for PM raft and endocytic studies. Caveolae at PM were visualized using transmission electron microscopy. Cdc42 activation was measured and caveolin-1 knockdown was performed using siRNAs.

Results: Prom2 expression in HSF and CHO cells caused extensive Prom2-positive protrusions that co-localized with lipid raft markers. Prom2 expression significantly decreased caveolae at the PM, reduced caveolar endocytosis and increased caveolin-1 phosphorylation. Prom2 expression also inhibited Cdc42-dependent fluid phase endocytosis via decreased Cdc42 activation. Effects on endocytosis were reversed by addition of cholesterol. Knockdown of caveolin-1 by siRNA restored Cdc42 dependent fluid phase endocytosis in Prom2-expressing cells.

Conclusions: Prom2 protrusions primarily localize to lipid rafts and recruit cholesterol into protrusions and away from caveolae, leading to increased phosphorylation of caveolin-1, which inhibits Cdc42-dependent endocytosis. This study provides a new insight for the role for prominins in the regulation of PM lipid organization.
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http://dx.doi.org/10.1016/j.bbrc.2013.03.097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659420PMC
May 2013

Primary headache in children and adolescents: update on pharmacotherapy of migraine and tension-type headache.

Neuropediatrics 2013 Feb 9;44(1):3-19. Epub 2013 Jan 9.

Department of Paediatric Neurology and Developmental Medicine, Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.

Primary headache disorders are frequently encountered in the pediatric population. The therapeutic approach consists of a multimodal program, including lifestyle modification, psychotherapeutic intervention, pharmacotherapy, and complementary measures. This systematic review focuses on the pharmacotherapy of pediatric migraine and tension-type headache (TTH). In addition to the general treatment principles, the results of 33 clinical reports published on the topic since 2008 are outlined in detail. Furthermore, a tabular summary of previously investigated agents not studied since 2008 is given, as is an overview of promising pharmacologic approaches so far only evaluated in adults. A variety of pharmacologic options is available, but high-quality evidence is limited to single agents. At this time, approval is restricted to four triptans and flupirtine for the symptomatic treatment of pediatric acute migraine and TTH, respectively. No agent has been approved for the prevention of pediatric primary headaches. This review does not grade the drugs hierarchically because the complex profiles of many agents differ only slightly or even overlap. However, a detailed expert opinion is provided. On the basis of the outlined facts, the team of physician, patient, and parents has to decide on the most appropriate regimen for the individual situation in the sense of personalized medicine.
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http://dx.doi.org/10.1055/s-0032-1330856DOI Listing
February 2013

[Not Available].

MMW Fortschr Med 2011 Jan;153(Suppl 1):21-5

Boehringer Ingelheim GmbH & Co. KG Medical Affairs Germany, Binger Str. 173, 55218, Ingelheim am Rhein, Deutschland.

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http://dx.doi.org/10.1007/BF03367582DOI Listing
January 2011

Mirror movements in healthy humans across the lifespan: effects of development and ageing.

Dev Med Child Neurol 2010 Dec 11;52(12):1106-12. Epub 2010 Oct 11.

Institute of Clinical Radiology, Grosshadern Campus, Ludwig-Maximilians-University Munich, Germany.

Aim: mirror movements are a transient phenomenon during childhood, which decrease in intensity with motor development. An increasing inhibitory competence resulting in the ability of movement lateralization is thought to be the underlying mechanism. We aimed to quantify unintended mirror movements systematically across the lifespan and to investigate the influences of age, sex, handedness, and task frequency.

Method: a total of 236 participants (127 females, 109 males; 216 right-handed, 20 left-handed; age range 3-96y, median 25y 8mo) first performed four clinical routine tests while mirror movements were rated by the observer. They were then asked to hold a force transducer in each hand between the thumb and index finger and to perform oscillatory grip force changes in one hand, while the other hand had to prevent the force transducer from dropping.

Results: age showed a strong nonlinear effect on the mirror-movement ratio (the amplitude ratio of the mirror and active hand, adjusted by the respective maximum grip force). Initially, there was a steep decline in the mirror-movement ratio during childhood and adolescence, followed by a gradual rise during adulthood. Males had lower mirror-movement ratios than females. The high-frequency condition triggered lower mirror-movement ratios. No significant differences of mirror movements between dominant and non-dominant hand, or left- and right-handed participants, were found.

Interpretation: this study provides, for the first time to our knowledge, normative values of mirror movements across the lifespan that can aid differentiation between physiological and pathological mirror movements.
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http://dx.doi.org/10.1111/j.1469-8749.2010.03766.xDOI Listing
December 2010

Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress.

Cardiovasc Res 2010 Nov 18;88(2):360-6. Epub 2010 Jun 18.

Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.

Aims: Humanin (HN) is a 24-amino acid peptide that has been shown to have an anti-apoptotic function against neuronal cell death caused by Alzheimer's disease. Increased oxidative stress, one of the major factors contributing to this cell death, also plays an important role in the inflammatory process of atherosclerosis. The current study was designed to test the hypothesis that HN is expressed in the human vascular wall and may protect against oxidative stress.

Methods And Results: HN expression in the vascular wall was detected by immunostaining in the endothelial cell layer of human internal mammary arteries (n = 5), atherosclerotic coronary arteries (n = 17), and sections of the greater saphenous vein (n = 3). HN mRNA was expressed in the human aortic endothelial cells (HAECs). Cytoprotective effects of HN against oxidative stress were tested in vitro in HAECs. Pre-treatment with 0.1 µM HN reduced oxidized LDL (Ox-LDL)-induced (i) formation of reactive oxygen species by 50%, (ii) apoptosis by ∼50% as determined by TUNEL staining, and (iii) formation of ceramide, a lipid second messenger involved in the apoptosis signalling cascade, by ∼20%.

Conclusion: The current study demonstrates for the first time the expression of HN in the endothelial cell layer of human blood vessels. Exogenous addition of HN to endothelial cell cultures was shown to be effective against Ox-LDL-induced apoptosis. These findings suggest that HN may play a role and may have a protective effect in early atherosclerosis in humans.
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http://dx.doi.org/10.1093/cvr/cvq191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952532PMC
November 2010

The Justy mutation identifies Gon4-like as a gene that is essential for B lymphopoiesis.

J Exp Med 2010 Jul 7;207(7):1359-67. Epub 2010 Jun 7.

Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.

A recessive mutation named Justy was found that abolishes B lymphopoiesis but does not impair other major aspects of hematopoiesis. Transplantation experiments showed that homozygosity for Justy prevented hematopoietic progenitors from generating B cells but did not affect the ability of bone marrow stroma to support B lymphopoiesis. In bone marrow from mutant mice, common lymphoid progenitors and pre-pro-B cells appeared normal, but cells at subsequent stages of B lymphopoiesis were dramatically reduced in number. Under culture conditions that promoted B lymphopoiesis, mutant pre-pro-B cells remained alive and began expressing the B cell marker CD19 but failed to proliferate. In contrast, these cells were able to generate myeloid or T/NK precursors. Genetic and molecular analysis demonstrated that Justy is a point mutation within the Gon4-like (Gon4l) gene, which encodes a protein with homology to transcriptional regulators. This mutation was found to disrupt Gon4l pre-mRNA splicing and dramatically reduce expression of wild-type Gon4l RNA and protein. Consistent with a role for Gon4l in transcriptional regulation, the levels of RNA encoding C/EBPalpha and PU.1 were abnormally high in mutant B cell progenitors. Our findings indicate that the Gon4l protein is required for B lymphopoiesis and may function to regulate gene expression during this process.
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http://dx.doi.org/10.1084/jem.20100147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901076PMC
July 2010

A serious refractive multifocal intraocular lens complication in Meniere's disease.

Optom Vis Sci 2010 Jun;87(6):448-9

Department of Ophthalmology, University of Saarland, Homburg/Saar, Germany.

Purpose: To report an unfortunate case of patient selection for multifocal intraocular lens (MIOL) implantation.

Methods: Interventional case report.

Results: A 69-year-old woman with bilateral corticonuclear cataract underwent uneventful phacoemulsification with diffractive MIOL implantation within 1 week. She reported no previous medical history. A few days later she had persisting dizziness and experienced extreme photic phenomena, which progressively deteriorated. After intensive conversation, we discovered that our patient had a medical history of Meniere's disease. Bilateral intraocular lens exchange surgery was performed. One week after monofocal intraocular lens implantation, the patient was satisfied with the final visual outcome and did not report any visual complaints.

Conclusions: Retinocortical processing of visual information is impaired in patients with peripheral vestibular disorders such as Meniere's disease. Therefore, these patients are probably not good candidates for MIOL implantation, which requires an intact sensory system with rigorous visuovestibular interaction.
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http://dx.doi.org/10.1097/OPX.0b013e3181d9f645DOI Listing
June 2010

Impact of fibronectin on surface properties of intraocular lenses.

Graefes Arch Clin Exp Ophthalmol 2009 Sep 4;247(9):1277-83. Epub 2009 Jul 4.

Department of Ophthalmology, University of Saarland Hospital, 66421 Homburg, Saar, Germany.

Purpose: Physical properties of intraocular lens (IOL) surfaces determine biocompatibility. IOL hydrophobicity of commercially available IOLs with and without fibronectin (FN) coating can be determined by surface contact angle (SCA) measurements. SCA data of IOLs may allow for a rational selection of an IOL type as a function of underlying eye disease.

Setting: University Hospital of Saarland, Homburg (Saar), Germany

Methods: Thirteen IOL types were tested. IOLs were made of poly(methyl methacrylate)(PMMA), acrylate, or silicone. Select IOLs were surface modified by the manufacturer with heparin or a polysaccharide coating. SCA values of IOLs, either uncoated or precoated with FN, were determined using the sessile water drop method.

Results: SCA values ranged from 61.3 to 116.1 degrees for unmodified IOLs, with PMMA IOLs being more hydrophilic (median SCA, 74.1 degrees ), silicone IOLs more hydrophobic (median SCA, 113.3 degrees ), and acrylate IOLs intermediate (median SCA, 86.6 degrees ). Upon FN coating, all genuine acrylate lenses became significantly more hydrophilic while this effect was either nonsignificant or opposite on some PMMA and silicon IOLs. Heparin or polysaccharide surface modification resulted in significantly reduced SCA values. On acrylate IOLs, SCA values did not correlate with the aqueous content of the material.

Conclusions: This study associates IOL materials, surface modifications, and the role of FN preadsorption with SCA values reflecting surface hydrophobicity versus hydrophilicity. It provides a rationale for specific IOL selection as a function of the clinical setting, and a basis for IOL development using tailored surface physicochemistry to enhance biocompatibility and to reduce susceptibility to implant infection.
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http://dx.doi.org/10.1007/s00417-009-1130-6DOI Listing
September 2009

DC photoelectron gun parameters for ultrafast electron microscopy.

Microsc Microanal 2009 Aug;15(4):298-313

Department of Physics (M/C 273), University of Illinois at Chicago, 845 W. Taylor Street, Chicago, IL 60607-7059, USA.

We present a characterization of the performance of an ultrashort laser pulse driven DC photoelectron gun based on the thermionic emission gun design of Togawa et al. [Togawa, K., Shintake, T., Inagaki, T., Onoe, K. & Tanaka, T. (2007). Phys Rev Spec Top-AC 10, 020703]. The gun design intrinsically provides adequate optical access and accommodates the generation of approximately 1 mm2 electron beams while contributing negligible divergent effects at the anode aperture. Both single-photon (with up to 20,000 electrons/pulse) and two-photon photoemission are observed from Ta and Cu(100) photocathodes driven by the harmonics (approximately 4 ps pulses at 261 nm and approximately 200 fs pulses at 532 nm, respectively) of a high-power femtosecond Yb:KGW laser. The results, including the dependence of the photoemission efficiency on the polarization state of the drive laser radiation, are consistent with expectations. The implications of these observations and other physical limitations for the development of a dynamic transmission electron microscope with sub-1 nm.ps space-time resolution are discussed.
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http://dx.doi.org/10.1017/S1431927609090266DOI Listing
August 2009

High-power, femtosecond, thermal-lens-shaped Yb:KGW oscillator.

Opt Express 2008 Jun;16(12):8629-40

Department of Physics (m/c 273), University of Illinois at Chicago, 845 W. Taylor Street (rm. 2236), Chicago, IL 60607-7059, USA.

Thermal lens shaping for astigmatism compensation is extended to a high-power, diode-pumped, Yb:KGW laser by employing a gain crystal geometry designed for efficient polarized pumping. The 63MHz oscillator is soliton mode-locked with the aid of a saturable Bragg reflector to yield 250fs (347fs) pulses at an output power of 3.5W (5W). Frequency doubling of the 250fs pulses with an intrinsic efficiency >60% provides 1.65W of average green power.
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http://dx.doi.org/10.1364/oe.16.008629DOI Listing
June 2008

Influence of fibronectin on the adherence of Staphylococcus epidermidis to coated and uncoated intraocular lenses.

J Cataract Refract Surg 2008 Mar;34(3):497-504

Department and Hospital of Ophthalmology, University of Saarland Hospital, Homburg/Saar, Germany.

Purpose: To determine the effect of the modification of intraocular lens (IOL) surface properties on the adhesion of Staphylococcus epidermidis caused by fibronectin (FN) as the predominant proadhesive glycoprotein of the eye's initial foreign body reaction.

Setting: University of Saarland, Homburg/Saar, Germany.

Methods: Eleven IOL types were tested. The IOLs were of poly(methyl methacrylate), acrylate, or silicone. Some were surface modified with heparin or polysaccharide coating. The IOLs, unadsorbed or preadsorbed with fibronectin (FN), were incubated with [(3)H]-thymidine-labeled S epidermidis Rp62a, and the amount of adherent microorganisms was determined.

Results: Attachment of S epidermidis adhesion to various types of IOLs, both unadsorbed and FN precoated, varied significantly. The attachment to highly adhesive IOLs was almost 4-fold greater than that to low-adhesive IOLs. Attachment to FN precoated IOLs was generally enhanced compared with attachment to unadsorbed IOLs. Heparin surface modification resulted in no or a modest reduction in bacterial adhesion compared with unmodified IOLs. Bacterial adhesion was highly statistically significantly less on IOLs with polysaccharide surface modification.

Conclusions: There was significant variability in S epidermidis adhesion to IOLs as a function of design, material, surface modification, and FN preadsorption. Application of the findings may foster new developments to further reduce the major complication in cataract surgery, infective endophthalmitis.
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http://dx.doi.org/10.1016/j.jcrs.2007.10.042DOI Listing
March 2008

High-resolution, flat-field, plane-grating, f/10 spectrograph with off-axis parabolic mirrors.

Appl Opt 2007 Jun;46(16):3095-101

Department of Physics (M/C 273), University of Illinois at Chicago, Chicago, Illinois 60607-7059, USA.

A high-resolution, flat-field, plane-grating, f/10 spectrometer based on the novel design proposed by Gil and Simon [Appl. Opt. 22, 152 (1983)] is demonstrated. The spectrometer design employs off-axis parabolic collimation and camera mirrors in a configuration that eliminates spherical aberrations and minimizes astigmatism, coma, and field curvature in the image plane. In accordance with theoretical analysis, the performance of this spectrometer achieves a high spatial resolution over the large detection area, which is shown to be limited only by the quality of its optics and their proper alignment within the spatial resolution of a 13 microm x 13 microm pixelated CCD detector. With a 1500 lines/mm grating in first order, the measured spectral resolving power of lambda/Dlambda = 2.5(+/-0.5) x 10(4) allows the clear resolution of the violet Ar(I) doublet at 419.07 and 419.10 nm.
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http://dx.doi.org/10.1364/ao.46.003095DOI Listing
June 2007

The RIN: an RNA integrity number for assigning integrity values to RNA measurements.

BMC Mol Biol 2006 Jan 31;7. Epub 2006 Jan 31.

Agilent Technologies, Hewlett-Packard-Strasse 8, 76337 Waldbronn, Germany.

Background: The integrity of RNA molecules is of paramount importance for experiments that try to reflect the snapshot of gene expression at the moment of RNA extraction. Until recently, there has been no reliable standard for estimating the integrity of RNA samples and the ratio of 28S:18S ribosomal RNA, the common measure for this purpose, has been shown to be inconsistent. The advent of microcapillary electrophoretic RNA separation provides the basis for an automated high-throughput approach, in order to estimate the integrity of RNA samples in an unambiguous way.

Methods: A method is introduced that automatically selects features from signal measurements and constructs regression models based on a Bayesian learning technique. Feature spaces of different dimensionality are compared in the Bayesian framework, which allows selecting a final feature combination corresponding to models with high posterior probability.

Results: This approach is applied to a large collection of electrophoretic RNA measurements recorded with an Agilent 2100 bioanalyzer to extract an algorithm that describes RNA integrity. The resulting algorithm is a user-independent, automated and reliable procedure for standardization of RNA quality control that allows the calculation of an RNA integrity number (RIN).

Conclusion: Our results show the importance of taking characteristics of several regions of the recorded electropherogram into account in order to get a robust and reliable prediction of RNA integrity, especially if compared to traditional methods.
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http://dx.doi.org/10.1186/1471-2199-7-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413964PMC
January 2006

Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces.

Nucleic Acids Res 2005 Mar 30;33(6):e56. Epub 2005 Mar 30.

Array s/IMAGE, Genexpress, Functional Genomics and Systems Biology for Health LGN-UMR 7091, CNRS and Pierre and Marie Curie University of Paris 6, 7, rue Guy Môquet, 94801 Villejuif, France.

While it is universally accepted that intact RNA constitutes the best representation of the steady-state of transcription, there is no gold standard to define RNA quality prior to gene expression analysis. In this report, we evaluated the reliability of conventional methods for RNA quality assessment including UV spectroscopy and 28S:18S area ratios, and demonstrated their inconsistency. We then used two new freely available classifiers, the Degradometer and RIN systems, to produce user-independent RNA quality metrics, based on analysis of microcapillary electrophoresis traces. Both provided highly informative and valuable data and the results were found highly correlated, while the RIN system gave more reliable data. The relevance of the RNA quality metrics for assessment of gene expression differences was tested by Q-PCR, revealing a significant decline of the relative expression of genes in RNA samples of disparate quality, while samples of similar, even poor integrity were found highly comparable. We discuss the consequences of these observations to minimize artifactual detection of false positive and negative differential expression due to RNA integrity differences, and propose a scheme for the development of a standard operational procedure, with optional registration of RNA integrity metrics in public repositories of gene expression data.
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http://dx.doi.org/10.1093/nar/gni054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1072807PMC
March 2005

Determination of albuminuria in the urine of diabetics for prevention and control of diabetic nephropathy.

GMS Health Technol Assess 2005 Nov 2;1:Doc04. Epub 2005 Nov 2.

Verbund Katholischer Kliniken Düsseldorf gGmbH, Düsseldorf, Deutschland.

The Issue: Diabetes has become the main cause of endstage renal disease. The costs for the treatment of diabetic patients with endstage renal disease have increased in the last years and have become a relevant economic topic of the health service. The first unspecific predictor of a diabetic nephropathy is an albuminuria. The screening for diabetic nephropathy uses microalbuminuria as a proof.

Objectives: What significance does the determination of albuminuria have on the precaution and course-control of the diabetic nephropathy?a) in type 1 diabetic patientsb) in type 2 diabetic patientsWhich is an appropriate time to determine the albuminuria for the purpose of precaution and course-control of the diabetic nephropathy?a) in type 1 diabetic patientsb) in type 2 diabetic patientsWhich method of testing is most effective concerning economic and medical aspects?

Methods: Published literature from 1998 up to 2004 was identified by searching in the most important databases. Most of the guidelines were found by hand searching in the internet.

Results: Of 2,792 citation titles and abstracts examined, 274 articles were retrieved for full-text review. Five metaanalyses and reviews, one review about clearing of guidelines (regarding 18 international guidelines) and four guidelines met the inclusion criteria for screening for microalbuminuria and type 1 diabetes. Seven metaanalyses, one HTA report, one review about clearing of guidelines (regarding 17 international guidelines), and seven guidelines met the inclusion criteria for screening for microalbuminuria and type 2 diabetes. At the moment, the determination of albuminuria still has a great significance because it is recommended in most published literature and guidelines. The time to determine the albuminuria depends on the age of the patients and their type of diabetes. Type 2 diabetic patients should start the determination when the diabetes is diagnosed whereas the determination is recommended five years later when type 1 diabetic patients are concerned. Most guidelines recommend a screening for microalbuminuria every year.

Discussion And Conclusion: All guidelines and most of the literature recommend this screening. However, these recommendations are only based on expert consensus. The specificity of this screening is rather low. False positive tests in type 2 diabetic patients will cause psychological problems. A positive test leads to the recommendation to achieve "normal blood pressure" and "normoglycaemia" - but this applies to each diabetic patient. Based on these facts, the screening for albuminuria in type 1 or type 2 diabetes patients cannot be recommended as long as benefit has not been demonstrated by large, clinical, controlled trials. Without an evidence of the benefit, this screening cannot be economic.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011320PMC
November 2005