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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 | Investigating cervical spinal cord structure using axial diffusion tensor imaging显示文摘 | Simon JH Geoffrey JM | 2002 | Neurolmage2002，16，1： | 1 |
| 3 | Investigating cervical spinal cord structure using axial diffusion tensor imaging显示文摘 | Claudia AM Simon JH Geoffrey JM | 2002 | NeuroImage2002，16，1： | 1 |
| 4 | Investigating cervical spinal cord structure using axial diffusion tensor imaging显示文摘 | Claudia AM Simon JH Geoffrey JM | 2002 | NeuroImage2002，16，1： | 1 |
| 5 | High-Sensitivity Cardiac Troponin in the Distinction of Acute Myocardial Infarction From Acute Cardiac Noncoronary Artery Disease显示文摘 | Philip Haaf Beatrice Drexler Tobias Reichlin Raphael Twerenbold Miriam Reiter Julia Meissner Nora Schaub Claudia Stelzig Michael Freese Amely Heinzelmann Christophe Meune Cathrin Balmelli Heike Freidank Katrin Winkler Kris Denhaerynck Willibald Hochholzer | 2012 | Circulation2012，，1： | 1 |
| 6 | Human α-Defensins HNPs 1,-2,and -3 in Renal Cell Carcinoma-influence on tumor cell proliferation显示文摘 | Claudia AM Jasmina ML Tatjana K | 2002 | AM J Pathol2002，160，4： | 1 |
| 7 | Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America显示文摘BACKGROUND There has been an increase in cases of inflammatory bowel disease(IBD)in recent years.There is also greater access and availability of immunosuppressive and biological agents,which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing.Tuberculosis(TB)remains a public health problem,and it has a high incidence in several countries.Therefore,knowledge of the risk of developing TB in patients with IBD is important.AIM To evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODS A standard questionnaire included demographic variables,clinical aspects of IBD disease,history of active TB during treatment,active TB characteristics and evolution,initial screening and results and time from the start of anti-tumor necrosis factor alpha(TNFα)to TB development.RESULTS Azathioprine,anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence.The TNFα blockers increased the relative risk of developing active TB compared to other treatments.All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB.After adjustment for sex,age,type of IBD and latent TB,anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment.Late TB,which was diagnosed 3 mo after the start of anti-TNFα,was the most frequent.CONCLUSION Treatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America.This risk was increased when anti-TNFα was combined with azathioprine.The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection. | Flora Maria Lorenzo Fortes Ney Boa Sorte Victor D Mariano Laila D Andrade Fernanda A Oliveira Monique CA Santos Claudia Ivanilda N dos Santos Catharina A Passos Mila P Pacheco Valdiana C Surlo Neogelia P de Almeida Jaciane AM Fontes Andrea M Pimentel Raquel Rocha Genoile Oliveira Santana | 2020 | World Journal of Gastroenterology2020，26，44： | 1 |
| 8 | Atypical visual orienting to eye gaze and arrow cues in children with high functioning Autism Spectrum Disorder显示文摘 | Johannes EA Claudia PA Hiske AM | | 0，，02： | 1 |
| 9 | The loss of PSP toxin production in a formerly toxic Alexandrium lusitanicum clone 显示文摘 | Claudia AM David K Susana F | 2003 | Toxicon2003，43，： | 1 |
| 10 | Triggering of sudden death from cardiac causes by vigorous exertion显示文摘 | Christine MA Murray AM Claudia UC | 2000 | N Engl J Med2000，343，： | 1 |
| 11 | Defective removal of ribonucleotides from DNA promotes systemic autoimmunity显示文摘 | Günther Claudia Kind Barbara Reijns Martin AM Berndt Nicole Martinez-Bueno Manuel Wolf Christine Tüngler Victoria Chara Osvaldo Lee Young Ae Hübner Norbert Bicknell Louise Blum Sophia Krug Claudia Schmidt Franziska Kretschmer Stefanie Koss | 2015 | Journal of Clinical Investigation2015，，1： | 1 |
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