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| 1 | Constitutive STAT3 phosphorylation and IL-6/IL-10 co-expression are associated with impaired T-cell function in tuberculosis patients显示文摘T-cells critically contribute to protection against Mycobacterium tuberculosis infection,and impaired T-cell responses can lead to disease progression.Pro-inflammatory and immunosuppressive cytokines affect T-cells,and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function.Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases.We characterized blood samples from tuberculosis patients(n=28)and healthy contacts(n=28)from Ghana for M.tuberculosis-specific T-cell responses,constitutive cytokine production,and SOCS3 and pSTAT3 expression.Lentiviral modulation of primary CD4+T-cells was performed to determine the effects of SOCS3 on T-cell functions.T-cells from tuberculosis patients expressed higher levels of IL-10 and IL-6 and lower levels of T helper type(TH)17 cytokines after M.tuberculosis-specific stimulation compared to healthy contacts.In addition,tuberculosis patients had higher IL-10 and IL-6 levels in the supernatants of non-stimulated immune cells and plasma samples compared to healthy contacts.Notably,aberrant cytokine expression was accompanied by high constitutive pSTAT3 levels and SOCS3 expression in T-cells.Multivariate analysis identified an IL-6/IL-10 co-expression-based principal component in tuberculosis patients that correlated with high pSTAT3 levels.SOCS3 contributed to a regulatory component,and tuberculosis patients with high SOCS3 expression showed decreased TH1 cytokine expression and impaired IL-2-induced STAT5 phosphorylation.SOCS3 over-expression in primary CD4+T-cells confirmed the SOCS3 inhibitory function on IL-2-induced STAT5 phosphorylation.We conclude that constitutive pSTAT3 and high SOCS3 expression are influential factors that indicate impaired T-cell functions in tuberculosis patients. | Kirstin Harling Ernest Adankwah Alptekin Güler Anthony Afum-Adjei Awuah Louis Adu-Amoah Ertan Mayatepek Ellis Owusu-Dabo Norman Nausch Marc Jacobsen | 2019 | Cellular & Molecular Immunology2019，16，3： | 15 |
| 2 | Therapy-refractory gastrointestinal motility disorder in a child with c-kit mutations显示文摘Constipation and fecal impaction are frequent and distressing complaints in pediatric gastroenterology. Especially in neurologically handicapped children, treatment of severe forms of slow-transit constipation (STC) can be difficult. In the majority of cases, STC is of unknown etiology. However, in recent years, there is growing evidence that interstitial cells of Cajal (ICCs), which serve as electrical pacemakers and generate spontaneous electrical slow waves in the gastrointestinal tract, might play an important role in the pathophysiology of STC. It remains unclear whether morphological ICC alterations seen in affected patients are based on congenital developmental anomalies, or whether they are a consequence of long-term constipation with secondary damage of the gastrointestinal nervous system. To the best of our knowledge, we present the first case of a patient with histological alterations in ICC morphology who displayed multiple alterations of c-kit at the level of mRNA. The protein encoded by c-kit is the receptor tyrosine kinase Kit (CD117), which is crucial for development and function of ICCs. Therefore, these findings provide a new explanation for congenital alterations of ICC development that result in gastrointestinal motility disorders. | Christian Breuer Jun Oh Gerhard J Molderings Michael Schemann Birgit Kuch Ertan Mayatepek Rüdiger Adam | 2010 | World Journal of Gastroenterology2010，16，34： | 7 |
| 3 | 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 |
| 4 | Tetrahydrobiopterin responsiveness in phenylketonuria differs between patients with the same genotype显示文摘 | Lindner M Haas D Mayatepek E | 2001 | Mol Genet Metsb2001，73，1： | 1 |
| 5 | Sareosinaemia in a patient with severe progressive neurological damage and hypertrophic cardiomyopathy 显示文摘 | Meissner T Mayatepek E | 1997 | J Inherit Metab Dis1997，20，5： | 1 |
| 6 | Hereditary sensory andautonomic neuropathy with autonomic crises : A Turkish variant offamilial dysautonomia? 显示文摘 | Koy A Freynhagen R Mayatepek E | 2012 | J Child Neurol2012，27，2： | 1 |
| 7 | Mevalonate kinase deficiency: enlarging the clinical and biochemical spectrum 显示文摘 | Prietsch V Mayatepek E Krastel H | 2003 | Pediatrics2003，111，： | 1 |
| 8 | Macrocephaly as the initial manifestation of glutaryl-CoA-dehydrogenasedeficiency(glutaricaciduriatypeⅠ)显示文摘 | Trefz FK Hoffmann GF Mayatepek E | | 0，，11： | 1 |
| 9 | Wolman disease due to homozygosity for a novel truncated variant of lysosomal acid lipase(351 insA)associated with complete in situ acid lipase deficiency显示文摘 | Seedorf U Muntoni S Mayatepek E | | 0，，1： | 1 |
| 10 | Role of leukotrienes as indicators of the inflammatory demyelinating reaction in x-linked cerebral adrenoleukodystrophy显示文摘 | Mayatepek E Baumann M Meissner T | | 0，，10： | 1 |
| 11 | Benzydamine metabolism in vivo is impaired in patients with deficiency of flavin-containing monooxygenase 3显示文摘 | Mayatepek E Flock B Zschocke J | 2004 | Pharmacogenetics2004，14，11： | 1 |
| 12 | Fatal genetic defect causing Wolman disease显示文摘 | Mayatepek E Seedorf U Wiebusch H | | 0，，01： | 1 |
| 13 | Mevalonate kinase deficiency:enlarging the clinical and biochemical spectrum显示文摘 | Prietsch V Mayatepek E Krastel H | 2003 | Pediatrics2003，111，2： | 1 |
| 14 | Molecular genetics of type 1 glycogen storage disease 显示文摘 | Janecke AR Mayatepek E Utermann G | 2001 | Mol Genet Metab2001，73，： | 1 |
| 15 | Inborn errors of carbohydrate metabolism显示文摘 | Mayatepek E Hoffmann B Meissner T | 2010 | Best Pract Res Clin Gastroentero12010，24，5： | 1 |
| 16 | Sensitivity of electrospray-tandem mass spectrometry using the phenylalanine-tyrosine-ratio for differential diagnisis of hyperphenylalaninemia in neonates 显示文摘 | Schulze A Kohlmueller D Mayatepek E | 1999 | Clin Chim Acta1999，283，12： | 1 |
| 17 | Management and outcome in 75 individuals with long-chain fatty acid oxidation defects: results from a workshop显示文摘 | U. Spiekerkoetter M. Lindner R. Santer M. Grotzke M. R. Baumgartner H. Boehles A. Das C. Haase J. B. Hennermann D. Karall H. Klerk I. Knerr H. G. Koch B. Plecko W. R?schinger K. O. Schwab D. Scheible F. A. Wijburg J. Zschocke E. Mayatepek U. Wendel | 2009 | Journal of Inherited Metabolic Disease2009，，4： | 1 |
| 18 | Sensitivity of electrospray -tandem mass spectrometry using the Phenylalanine/tyrosine - ratio fordefferemtial diagnosis of hyperphenylalaninemia in neonates 显示文摘 | Schulze A Kohlmueller D Mayatepek E | 1999 | ClinChem Acta1999，283，： | 1 |
| 19 | Biochemical and molecular studies in mild flavin monoooxygenase 3 deficiency 显示文摘 | Zschocke J Mayatepek E | 2000 | J Inherit Metab Dis2000，23，4： | 1 |
| 20 | Benzydamine metabolism in vivo is im- paired in patients with deficiency of flavin-eontaining monooxy- genasc 3 显示文摘 | Mayatepek E Flock B | 2004 | Pharmacogenetics2004，14，11： | 1 |
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