Papers by Christian Seidl
International journal of molecular sciences, May 23, 2024
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Pediatric Research, Oct 1, 2005
The Journal of Clinical Endocrinology and Metabolism, Dec 1, 1997
Endocrine autoimmune disorders share susceptibility and resistance factors of the human leukocyte... more Endocrine autoimmune disorders share susceptibility and resistance factors of the human leukocyte antigen system on the short arm of chromosome 6, but other gene loci also contribute to predisposition and protection. Because the cytotoxic T lymphocyte antigen 4 (CTLA4) alanine-17 encoded by the CTLA4 gene on chromosome 2q33 confers susceptibility to Graves' disease, as well as to type 1 (insulin-dependent) diabetes mellitus , we investigated this dimorphism in the other endocrine autoimmune disorders: Hashimoto's thyroiditis and Addison's disease. We analyzed the CTLA4 exon 1 polymorphism (49 A/G) in 73 patients with Hashimoto's thyroiditis, 76 with Addison's disease, and 466 healthy controls. This dimorphism corresponds to an aminoacid exchange (Thr/Ala) in the leader peptide of the expressed protein. CTLA4 alleles were defined by PCR, single-strand conformational poly
Frontiers in Oncology, 2013
Allogeneic natural killer (NK) cells are used for adoptive immunotherapy after stem cell transpla... more Allogeneic natural killer (NK) cells are used for adoptive immunotherapy after stem cell transplantation. In order to overcome technical limitations in NK cell purification and activation, the following study investigates the impact of different variables on NK cell recovery, cytotoxicity, and T-cell depletion during good manufacturing practice (GMP)-grade NK cell selection. Forty NK cell products were derived from 54 unstimulated donor leukaphereses using immunomagnetic CD3 T-cell depletion, followed by a CD56 cell enrichment step. For T-cell depletion, either the depletion 2.1 program in single or double procedure (D2.1 1depl , n = 18; D2.1 2depl , n = 13) or the faster depletion 3.1 (D3.1, n = 9) was used on the Clini-MACS instrument. Seventeen purified NK cell products were activated in vitro by IL-2 for 12 days. The whole process resulted in a median number of 7.59 × 10 8 CD56 + CD3 − cells with both purity and viability of 94%, respectively. The T-cell depletion was significantly better using D2.1 1depl/2depl compared to D3.1 (log 4.6/log 4.9 vs. log 3.7; p < 0.01) and double procedure in two stages led always to residual T cells below 0.1%. In contrast D3.1 was superior to D2.1 1depl/2depl with regard to recovery of CD56 + CD3 − NK cells (68% vs. 41%/38%). Concomitant monocytes and especially IL-2 activation led to increased NK cell activity against malignant target cells compared to unstimulated NK cells, which correlated with both up-regulation of natural cytotoxicity receptors and intracellular signaling. Overall, wide variations in the NK cell expansion rate and the distribution of NK cell subpopulations were found. In conclusion, our results indicate that GMP-grade purification of NK cells might be improved by a sequential processing of T-cell depletion program D2.1 and D3.1. In addition NK cell expansion protocols need to be further optimized.
Gut, Nov 1, 1998
Background-Black tea is known to be a potent inhibitor of intestinal absorption of non-haem iron ... more Background-Black tea is known to be a potent inhibitor of intestinal absorption of non-haem iron at least in healthy subjects. Aims-To investigate this eVect in patients with genetic haemochromatosis, and, more importantly, the eVect of regular tea drinking on the accumulation of storage iron in these patients over one year. Patients-Investigations were carried out on 18 patients with clinically proven genetic haemochromatosis. For the study of storage iron accumulation, they were separated into a group instructed to drink a particularly tannin rich tea regularly with meals and a control group. Methods-Intestinal iron absorption from a test meal was measured using whole body counting. Body iron stores were evaluated quantitatively by exhaustive phlebotomy, using haemoglobin, saturation of serum iron binding capacity, and serum ferritin for the assessment of body iron status. Results-A significant reduction in iron absorption was observed when the test meal was accompanied by drinks of tea instead of water. In the tea drinking group, the increase in storage iron was reduced by about one third compared with that of the control group. Conclusions-Regular tea drinking with meals reduces the frequency of phlebotomies required in the management of patients with haemochromatosis.
Diabetes, Obesity and Metabolism, Feb 1, 2009
Aim-The region on chromosome 6p21 (IDDM1) confers the largest part of genetic susceptibility to t... more Aim-The region on chromosome 6p21 (IDDM1) confers the largest part of genetic susceptibility to type 1 diabetes (T1D) with particular human leucocyte antigen (HLA) alleles predisposing and others protecting from it. As T1D is primarily a "sporadic" disease, the pathophysiology must involve gene-environment interactions. We searched for indirect evidence for such major histocompatibility complex (MHC)-environment interactions by asking two questions: (i) can the degree of an HLA association vary over time periods? and (ii) if a prenatal event like an intrauterine infection-that might cluster in seasons-leads to differences of HLA associations in patients with particular birth months? Methods-We screened the Type 1 Diabetes Genetics Consortium (T1DGC) database (in addition our own database and the original UK, US and SCAND databases) for MHC DR-DQ and CTLA4 associations. First, we separated the groups of patients with onset of disease before 1980 in comparison with onset after 1980. Second, we analysed the data according to dates of birth (grouped in months). Not all patients' dates of birth or manifestation periods were available, leading to different group sizes. There were 282 patients analysed for manifestation periods and 329 for birth month. Results-The cohorts of manifestation before 1980 demonstrated a significantly lower frequency of DQ2/X (2 vs. 14.2%; p = 0.03). There was a trend for DQ8/x to be more frequent for manifestations before 1980 (34 vs. 21.6%; p < 0.10). Other alleles did not differ significantly. The months of birth were not evenly distributed. Significant deviations from the whole group were seen in August (DQ2/8 trough and DQx/x high), whereas birth in September was more frequent in DQ8/x or DQ8/8 carriers.
European Journal of Cardio-Thoracic Surgery, Oct 16, 2017
OBJECTIVES: Perioperative prophylaxis with cephalosporins reduces sternal wound infections (SWIs)... more OBJECTIVES: Perioperative prophylaxis with cephalosporins reduces sternal wound infections (SWIs) after cardiac surgery. However, more than 50% of coagulase-negative staphylococci, an important pathogen, are cephalosporin resistant. The aim of this study was to determine the impact of adjunctive vancomycin on SWIs in high-risk patients. METHODS: We conducted a pre-and postintervention study in an academic hospital. Preintervention (2010-2011), all patients received prophylaxis with 1.5 g of cefuroxime for 48 h. During the intervention period (2012-2013), high-risk patients additionally received 1 g of vancomycin. High-risk status was defined as body mass index < _18 or > _ 30 kg/m 2 , reoperation, renal failure, diabetes mellitus, chronic obstructive pulmonary disease or immunosuppressive medication. Time series analysis was performed to study SWI trends and logistic regression to determine the effect of adding vancomycin adjusting for high-risk status. RESULTS: A total of 3902 consecutive patients (n = 1915 preintervention and n = 1987 postintervention) were included, of which 1493 (38%) patients were high-risk patients. In the high-risk group, 61 of 711 (8.6%) patients had SWI before and 30 of 782 (3.8%) patients after the intervention. Focusing on deep SWI (DSWI), 33 of 711 (4.6%) patients had DSWI before and 13 of 782 (1.7%) patients afterwards; the absolute risk difference of 2.9% yielded a number-needed-to-treat of 34 to prevent 1 DSWI. Corrected for high-risk status, adding vancomycin significantly reduced the overall SWI rate (odds ratio 0.42, 95% confidence interval 0.26-0.67; P < 0.001) and the subset of DSWI (odds ratio 0.30, 95% confidence interval 0.14-0.62; P = 0.001). The rate of SWI in low-risk patients remained unchanged. CONCLUSIONS: Adding vancomycin to standard antibiotic prophylaxis in high-risk patients significantly reduced DSWI after cardiac surgery.
Journal of Translational Medicine, 2022
Background Safety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for... more Background Safety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being “warm glow”, hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally. Methods We enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire. Results Baseline physical and mental hea...
2018 IEEE 27th International Symposium on Industrial Electronics (ISIE), 2018
Optimizing energy usage is becoming an economic necessity for existing buildings. Non-invasive se... more Optimizing energy usage is becoming an economic necessity for existing buildings. Non-invasive sensors and sensor networks are key technologies for efficiently achieving this goal, since it is of utmost importance that existing hydraulic systems are not changed and the engineering effort for installation remains minimal. This paper presents a data-driven approach that should allow low-cost installation of sensors at arbitrary points of the building and then retrieve the structure of the hydraulic system from the recorded sensor values. The architecture as well as first preliminary results from field test buildings are presented.
16th Congress of the International Society for Forensic Haemogenetics (Internationale Gesellschaft für forensische Hämogenetik e.V.), Santiago de Compostela, 12–16 September 1995, 1996
Short tandem repeat loci (STR) are polymorphic markers that can be used for human identification ... more Short tandem repeat loci (STR) are polymorphic markers that can be used for human identification in forensic or paternity casework. We have investigated the polymorphism of the STR locus D21S11 in a german population sample.
Professor Steven G. E. Marsh, Anthony Nolan Research Institute, Royal Free Hospital, Pond Street,... more Professor Steven G. E. Marsh, Anthony Nolan Research Institute, Royal Free Hospital, Pond Street, London NW3 2QG, UK.Tel: +44 20 7284 8321; Fax: +44 20 7284 8331; e-mail: [email protected]; URLs: www.hla.alleles.org, www.anthonynolan.org/HIG,www.ebi.ac.uk/imgt/hladoi: 10.1111/j.1399-0039.2010.01553.x
Aspects of Latin Papers from the Seventh International Colloquium on Latin Linguistics Jerusalem 1993 1996 Isbn 3 85124 659 4 Pags 99 118, 1996
Transplant International, 2016
Clinical relevance of ELISA- and single antigen bead assay (SAB)-detected pre-transplant HLA anti... more Clinical relevance of ELISA- and single antigen bead assay (SAB)-detected pre-transplant HLA antibodies (SAB-HLA-Ab) for kidney graft survival was evaluated retrospectively in 197 patients transplanted between 2002 and 2009 at the University Clinic Frankfurt. Having adjusted for re-transplantation and delayed graft function a significantly increased risk for death censored graft loss was found in patients with pre-transplant SAB-HLA-Ab (HR: 4.46; 95% Cl: 1.47 to 13.48; P=0.008). The risk for increased graft loss was also significant in patients with pre-transplant SAB-HLA-Ab but without SAB-detected donor specific Ab (SAB-DSA) (4.91; 95% CL of 1.43 - 16.991; P=0.012). ELISA was not sufficient to identify pre-transplant immunized patients with an increased risk for graft loss. In immunized patients, graft loss was predominantly present in patients who received transplants with a mismatch on the HLA-DR locus. In conclusion, even if our study is limited due to small sample size, the results show an increased risk for long-term graft loss in patients with pre-transplant SAB-HLA, even in the absence of DSA. SAB-HLA-Ab positive patients, being negative in ELISA or CDC assay, might profit from a well HLA-DR-matched graft and intensified immunosuppression. This article is protected by copyright. All rights reserved.
2008 8th IEEE Conference on Nanotechnology, 2008
Abstract-As a prototype towards a single photon source we present a quantum-dot-based device, whi... more Abstract-As a prototype towards a single photon source we present a quantum-dot-based device, which is tunable and fully electrically pumped.łBoth the electrical pumping process and the manipulation of the emission wavelength of the quantum dots are independently ...
British Journal of Haematology - BRIT J HAEMATOL, 2000
The hepatitis C virus (HCV) has recently been implicated in the pathogenesis of several B-cell ly... more The hepatitis C virus (HCV) has recently been implicated in the pathogenesis of several B-cell lymphoproliferative disorders. In particular, anti-HCV antibodies and/or HCV RNA have been detected in most patients with type II mixed cryoglobulinaemia and in a large proportion of Italian patients with B-cell non-Hodgkin's lymphoma (NHL) (reviewed by Silvestri et al, 1996; Agnello, 1997; Ivanovski et al, 1998). Moreover, an asymptomatic monoclonal B-cell expansion has been demonstrated by molecular methods in < 20% of Italian patients with HCV-associated chronic liver disease (Franzin et al, 1995). The high prevalence of chronic HCV infection among patients with B-cell NHL has been observed primarily in Mediterranean countries, particularly in Italy (9±32%), where the prevalence of HCV carriers in the general population is quite high and ranges from 1% to 5 ́4%. A recent US study investigating predominantly Hispanic patients also showed a significantly higher prevalence of HCV infection in NHL patients (22%) than in age-matched controls (Zuckerman et al, 1997). However, other studies from the USA, Canada, Germany, the UK and France have not confirmed this association (reviewed by Germanidis et al, 1999). A possible explanation for this difference is the significantly lower prevalence of HCV infection in the general population of the latter countries. To test this last possibility, we investigated the prevalence of HCV infection in B-cell NHL patients from the Republic of Macedonia, which is characterized by a relatively high prevalence of HCV carriers within the general population (2 ́0%). We tested 112 consecutive patients with NHL (93 Macedonian and 19 Albanian) and a control group of 137 patients with other B-cell malignancies (38 with Hodgkin's disease, 43 with chronic lymphocytic leukaemia, nine with acute lymphoblastic leukaemia, 26 with multiple myeloma and one with WaldenstroÈm's macroglobulinaemia). The diagnosis was based on histological and immunohistochemical analysis of a lymph node and/or bone marrow biopsy according to the Revised European±American Classification (REAL) of lymphoid neoplasms. The serum samples were tested for antibodies to HCV by third-generation enzymelinked immunosorbent assay (ELISA) using commercially available kits and for HCV RNA by reverse transcriptase± polymerase chain reaction (RT±PCR) amplification of the 5 0 untranslated region of HCV. Table I summarizes the results for the different NHL subtypes and the controls. HCV infection was detected in only one patient with NHL (0 ́89%) and in one of the 137 patients with other B-cell malignancies (0 ́72%). Thus, our study demonstrates a low prevalence of HCV infection in patients with B-cell NHL from Macedonia and a lack of association between the two disorders. The comparable prevalence of HCV infection in the general population of Macedonia with that in Italy indicates that HCV infection requires additional environmental factors and/or a distinct genetic background to induce a malignant B-cell disorder. The same appears to be true for the benign HCV-associated B-cell lymphoproliferations, such as type II mixed cryoglobulinaemia, and the asymptomatic monoclonal B-cell expansions; both disorders were recently found to be significantly less prevalent in Japanese than in Italian patients with HCV-positive chronic liver disease (Pozzato et al, 1999). Therefore, it seems likely that HCV-associated lymphoproliferative disorders have a multifactorial aetiology, which includes additional, presently undetermined, genetic and environmental factors that may vary widely with geography.
Immunogenetics, 1992
HLA antigens, the major histocompatibility complex (MHC) antigens of humans, are required in disc... more HLA antigens, the major histocompatibility complex (MHC) antigens of humans, are required in discrimination by the immune system of foreign antigens from self (Unanue 1984; Bjorkman et al. 1987). The HLA class II antigens are polymorphic cell surface antigens composed of two transmembrane glycoproteins of M r 27000-29000 (/3 chain) and M r 33000-35000 (o~ chain) which associate soon after synthesis within the endoplasmic reticulum and are transported together to the surface (Kvist et al. 1982). Class II antigens are found primarily on B cells and macrophages, but are inducible in other cells by soluble factors such as interferon-3' (IFN3') and interleukin-4 (IL-4; Kaufman et al. 1984; Korman et al. 1985; Sette et al. 1987). These molecules act as restriction elements for presentation of foreign antigen to CD4-positive helper T cells and, at least in some cases, to cytotoxic T lymphocytes. In earlier studies, we showed that alternative splicing of HLA DQB1 transcripts generated distinct mRNAs which code for membrane bound and secreted DQB1 proteins (Briata et al. 1989). Furthermore, alternative splicing which deletes the transmembrane exon appeared to be associated with only a subset of DQB1 alleles. Though we have no direct evidence for their function, we suspect soluble class II molecules may contribute to the development and control of an immune response. Therefore, we set out to define more precisely allelic variation and tissue specificity in the generation of alternatively spliced DQB1 mRNAs (ATM), and to determine whether similar mRNAs for DRB transcripts could be found. For the analysis of alternative splicing, we developed an efficient and sensitive method to detect ATM and + TM mRNAs using cDNA made from total cytoplasmic RNA and amplified with specific primers using polymerase chain reaction (PCR; Mullis and Faloona 1987). HLA homozygous B lymphoblastoid cell lines
Human Immunology, 1999
Human endogenous retrovirus (HERV) long terminal repeat (LTR) elements contain regulatory sequenc... more Human endogenous retrovirus (HERV) long terminal repeat (LTR) elements contain regulatory sequences that can influence the expression of adjacent cellular genes, which may contribute to breakdowns of the immune function leading to autoimmune disease. Rheumatoid arthritis (RA) is associated with particular HLA-DR/DQ haplotypes that modulate the pathogenesis of this autoimmune disease. We have therefore studied a solitary LTR element (DQ-LTR3) of the HERV-K family at the HLA-DQB1 locus for a possible disease association among 228 RA patients and 311 unrelated blood donors. The DQ-LTR3 was significantly more frequent among patients (76% vs 33%, OR ϭ 5.07, p Ͻ 0.0001), with the majority of patients being heterozygous for the DQ-LTR3 (61% vs 22%, p Ͻ 0.0001). HLA-DRB1*04 positive patients did still differ for the presence of the DQ-LTR3 (88% vs 70%, OR ϭ 3.03, p Ͻ 0.001), with an increase of both DQ-LTR3 homozygous and heterozygous patients, when compared to DRB1*04 positive controls (p ϭ 0.0015). HLA-DR/DQ genotype analysis among HLA-DRB1*04 positive individuals revealed significantly more DQ-LTR3 homozygotes among HLA-DRB1*04-DQB1*03 homozygous patients (72% vs 27%, p ϭ 0.015), and the number of DQ-LTR3 homozygous (23% vs 19%) and heterozygous (66% vs 53%) individuals was also increased among HLA-DRB1*04 heterozygous patients (p ϭ 0.034). The presence of the DQ-LTR3 element increased both the relative risk and the positive predictive value for either DRB1*04-DQB1*03 positive/negative individuals when compared to the presence of HLA-DRB1*04-DQB1*03 alone. In conclusion, these data suggest that this DQ-LTR3 enhances susceptibility to RA.
Human Immunology, 2009
Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease. Although the precise mechanisms le... more Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease. Although the precise mechanisms leading to the destruction of islet  cells are unknown, diverse studies support a role of the CXCR3-binding chemokines. A combination of a case (n ϭ 447)-control (n ϭ 300) and family (n ϭ 221) analysis was performed to investigate the role of the CXCL9 (rs10336, rs3733236) and CXCL10 (rs3921, rs35795399 and rs8878) polymorphisms and their interaction with HLA high-risk haplotypes DQ2(DQA*0501-DQB*0201)-DQ8(DQA*0301-DQB*0302) in T1D. In addition, the mRNA expression of these genes and of the CXCR3 in peripheral blood mononuclear cells (PBMCs) of T1D patients was studied. In the family analysis, an overtransmission of the allele T and G of the polymorphisms rs35795399 and rs8878 in the whole group (p ϭ 0.0520 and p ϭ 0.0290, respectively) as well as in combination with the HLA-high risk haplotypes (p ϭ 0.0209 and 0.0340, respectively) were observed. In addition, the haplotype rs8878G-rs35795399T was more often transmitted from parents to affected offspring, whereas the haplotype rs8878A-rs35795399C was less often transmitted (p ϭ 0.0130 and p ϭ 0.0201, respectively). Nevertheless these associations did not remain significant after correction for multiple testing, and they could not be corroborated in the case-control analysis. Although we did not find an association of the CXCL9 and CXCL10 polymorphisms with type 1 diabetes in the German population, we cannot discard their role in other populations or other autoimmune diseases.
European Journal of Political Economy, 2004
Patrick Moyes, Christian Seidl and Tony Shorrocks have edited a volume that includes four fields ... more Patrick Moyes, Christian Seidl and Tony Shorrocks have edited a volume that includes four fields of investigation: theoretical research on inequality, experiments on distributional issues, statistical inference in research on inequality, and finally, poverty persistence and dynamics. The present review essay first summarizes the various papers and then offers a critical assessment.
Diabetologia, 2002
Type I (insulin-dependent) diabetes mellitus is a beta-cell selective immune-mediated disease wit... more Type I (insulin-dependent) diabetes mellitus is a beta-cell selective immune-mediated disease with a strong genetic background. Heritable susceptibility is conferred by at least 14 gene loci [1, 2], with the largest contribution from the human leukocyte antigen (HLA) region on chromosome 6, designated IDDM1 [3, 4]. This region contains several loci with a high degree of variability amongst which HLA DRB1, DQA1 and DQB1 have shown the strongest association with Type I diabetes [5]. Long terminal repeats (LTRs) are common retrovirus-related sequences spread throughout the hu-Diabetologia (2002) 45: 443±447
Uploads
Papers by Christian Seidl