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| 1 | Partial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation显示文摘AIM To investigate the relation of two different mutations to the outcome of partial external biliary diversion(PEBD)in severe bile salt export pump(BSEP) deficiency.METHODS Mutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney(HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatographytandem mass spectrometry. Wild-type and mutant BSEP transport of [~3H]-labeled taurocholate(TC) and taurochenodeoxycholate(TCDC) was assessed by vesicular transport assays.RESULTS A girl(at 2 mo) presented with pruritus, jaundice and elevated serum bile salts(BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919 del and the nonsense mutation p.R1235 X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy(age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032 R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives(< 5%). The patients' native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919 del and p.G1032 R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild-type BSEP transporter per minute, respectively.CONCLUSION In summary, our findings suggest that residual function of BSEP as well as substrate specificity influence the therapeutic effectiveness of PEBD in progressive familial intrahepatic cholestasis type 2(PFIC-2). | Philipp Ellinger Jan Stindt Carola Droge Katharina Sattler Claudia Stross Stefanie Kluge Diran Herebian Sander HJ Smits Martin Burdelski Sebastian Schulz-Jürgensen Antje Ballauff Jan Schulte am Esch Ertan Mayatepek Dieter Haussinger Ralf Kubitz Lutz Schmitt | 2017 | World Journal of Gastroenterology2017，23，29： | 4 |
| 2 | The constituent equation of piezoelectric bi- morphs显示文摘 | SMITS Jan G DALKE Susan I COONEY Thomas K | 1991 | Sensors and Actuator A1991，28，1： | 2 |
| 3 | Reproducible Long-term Disc Degeneration in a Large Animal Model显示文摘 | Roel J. W. Hoogendoorn Marco N. Helder Robert Jan Kroeze Ruud A. Bank Theo H. Smit Paul I. J. M. Wuisman | 2008 | Spine2008，，9： | 1 |
| 4 | Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European study on glycogen storage disease type I (ESGSD I)显示文摘 | Jan Peter Rake Gepke Visser Philippe Labrune James V. Leonard Kurt Ullrich G. Peter A. Smit | 2002 | European Journal of Pediatrics2002，，1： | 1 |
| 5 | The constituent equations of piezoelectric bimorphs 显示文摘 | Smits Jan G Dalke Susan I Thomas Cooney | 1991 | Sensors and Actuators A1991，28，： | 1 |
| 6 | Easy and Rapid Purification of Highly Active Nisin显示文摘 | André Abts Antonino Mavaro Jan Stindt Patrick J. Bakkes Sabine Metzger Arnold J. M. Driessen Sander H. J. Smits Lutz Schmitt Piero Andrea Temussi | 2011 | International Journal of Peptides2011，，： | 1 |
| 7 | Optimized bacterial production of nonglycosylated human transferrin and its half-molecules显示文摘 | Maarten H. de Smit Peter Hoefkens Gerard de Jong Jan van Duin Peter H. van Knippenberg Hendrik G. van Eijk | 1995 | International Journal of Biochemistry and Cell Biology1995，，8： | 1 |
| 8 | The Association Between Hearing Status and Psychosocial Health Before the Age of 70 Years: Results From an Internet-Based National Survey on Hearing显示文摘 | Janneke Nachtegaal Jan H. Smit Cas Smits Pieter D. Bezemer Johannes H. M. van Beek Joost M. Festen Sophia E. Kramer | 2009 | Ear and Hearing2009，，3： | 1 |
| 9 | Microbes from Raw Milk for Fermented Dairy Products显示文摘 | JAN T M W EMAN H E A HUGENHOLTZ J SMIT G | 2002 | Int Dairy J2002，12，： | 1 |
| 10 | Glycogen storage disease type Ia: recent experience with mutation analysis, a summary of mutations reported in the literature and a newly developed diagnostic flowchart显示文摘 | Jan Peter Rake Annelies M. ten Berge Gepke Visser Edwin Verlind Klary E. Niezen-Koning Charles H. C. M. Buys G. Peter A. Smit Hans Scheffer | 2000 | European Journal of Pediatrics2000，，5： | 1 |
| 11 | The constituent equation of piezoelectric bimor phs显示文摘 | SMITS JAN G SUSAN I Dalke Thomas K Cooney | 1991 | Sensors and Actuator1991，，28： | 1 |
| 12 | Near‐infrared fluorescence‐guided resection of colorectal liver metastases显示文摘 | Joost R. van der Vorst Boudewijn E. Schaafsma Merlijn Hutteman Floris P. R. Verbeek Gerrit‐Jan Liefers Henk H. Hartgrink Vincent T. H. B. M. Smit Clemens W. G. M. L?wik Cornelis J. H. van de Velde John V. Frangioni Alexander L. Vahrmeijer | 2013 | Cancer2013，，18： | 1 |
| 13 | Dyna micadmitta nce matrix of piezoelectriccantil ever bimor phs 显示文摘 | SMITS JAN G Arthur Ballato | 1994 | Journal of microelectromechanical system1994，3，3： | 1 |
| 14 | Intellectual ,Property Rights and Standardization:The Case of GSM 显示文摘 | Rudi Bekkers Bart Verspagen Jan Smits | 2002 | Telecommunications Policy2002，，26： | 1 |
| 15 | The constituent equations of piezoelectric heterogeneous bimorphs 显示文摘 | Smits Jan G Choi Wai-shing | 1991 | IEEE Trans Ultrason Ferroelectr Freq Control1991，38，3： | 1 |
| 16 | Intellectual Property Rights and Standardization:The Case of GSM显示文摘 | Rudi Bekkers Bart Verspagen Jan Smits | 2002 | Telecommunications Policy2002，，26： | 1 |
| 17 | Dynamicadmittance matrix of piezoelectriccantil ever bimor- phs显示文摘 | SMITS Jan G BALLATO Arthur | 1994 | Journal of Microelectromechanical System1994，3，3： | 1 |
| 18 | The bacterial surface layer provides protection against antimicrobial peptides显示文摘 | Fuente-Nú?ez C D Mertens Jan Smit J | | 0，，： | 1 |
| 19 | The constituent equations of piezoelectric bimorphs显示文摘 | Susan I Dalke Thomas IL Cooney | 1991 | Sensors and Actuators A1991，28，： | 1 |
| 20 | The constituent equations of piezoelectric bimorphs显示文摘 | JAN G SMITS SUSAN I DALKE | 1991 | Sensors and Actuators A1991，28，1： | 1 |
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