Publications by authors named "Thierfelder W"

Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and resistance to glucocorticoids in leukemia cells confers poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 patients newly diagnosed with ALL and found significantly higher expression of CASP1 (encoding caspase 1) and its activator NLRP3 in glucocorticoid-resistant leukemia cells, resulting from significantly lower somatic methylation of the CASP1 and NLRP3 promoters. Overexpression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished the glucocorticoid-induced transcriptional response and increased glucocorticoid resistance.

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Objectives: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, frequently associated with reduced bone mineral density. Serum 25-hydroxyvitamin D3 concentrations in NF1 adults are lower than in healthy controls in autumn respectively winter and are inversely correlated with the number of dermal neurofibromas. We investigated 25-hydroxyvitamin D3 levels in children and adults with neurofibromatosis type 1 in winter and summer and compared them to healthy controls to get more pathogenic insights in vitamin D3 metabolism in NF1 patients.

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Treatment-related toxicity can be life-threatening and is the primary cause of interruption or discontinuation of chemotherapy for acute lymphoblastic leukemia (ALL), leading to an increased risk of relapse. Mercaptopurine is an essential component of continuation therapy in all ALL treatment protocols worldwide. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) are known to have a marked effect on mercaptopurine metabolism and toxicity; however, some patients with wild-type TPMT develop toxicity during mercaptopurine treatment for reasons that are not well understood.

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DNA mismatch repair enzymes (for example, MSH2) maintain genomic integrity, and their deficiency predisposes to several human cancers and to drug resistance. We found that leukemia cells from a substantial proportion of children (∼11%) with newly diagnosed acute lymphoblastic leukemia have low or undetectable MSH2 protein levels, despite abundant wild-type MSH2 mRNA. Leukemia cells with low levels of MSH2 contained partial or complete somatic deletions of one to four genes that regulate MSH2 degradation (FRAP1 (also known as MTOR), HERC1, PRKCZ and PIK3C2B); we also found these deletions in individuals with adult acute lymphoblastic leukemia (16%) and sporadic colorectal cancer (13.

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The success of childhood vaccination against hepatitis B relies on persistence of immunity into adolescence and adulthood. In 2000, two hexavalent vaccines with a hepatitis B component (Hexavac, Infanrix hexa) were introduced in Germany. Hexavac was withdrawn in 2005 amidst concerns about its long-term hepatitis B protection.

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To inform current and future vaccination strategies, we describe the seroepidemiology of hepatitis B virus (HBV) infection in ten representative European countries using standardized serology that allowed international comparisons. Between 1996 and 2003, national serum banks were compiled by collecting residual sera or by community sampling; sera were then tested by each country using its preferred enzyme immunoassays and testing algorithm, and assay results were standardized. Information on current and past HBV vaccination programmes in each country was also collected.

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The European Sero-Epidemiology Network 2 (ESEN2) aimed to compare serological results of vaccine-preventable diseases across Europe. To ensure direct inter-country comparability of hepatitis A virus antibody (anti-HAV) measurements, a standardization panel of 150 sera was developed by a designated reference laboratory and tested by participating national laboratories using assays of choice; each country's results were subsequently regressed against those of the reference laboratory. Quantitatively, the assays were generally highly correlated (R2>0.

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Background: From May 2003 to May 2006, the Robert Koch Institute conducted the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Aim of this first nationwide interview and examination survey was to collect comprehensive data on the health status of children and adolescents aged 0 to 17 years.

Methods/design: Participants were enrolled in two steps: first, 167 study locations (sample points) were chosen; second, subjects were randomly selected from the official registers of local residents.

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Acute parvovirus B19 infection is a risk for pregnant women. After vertical transmission the infected fetus may develop hydrops fetalis. Since B19 infection occurs mainly during childhood, children represent a main source for virus transmission.

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Objective: To analyze vitamin D status based on serum 25-hydroxyvitamin D (25OHD) measurements, its determinants and health correlates in a representative sample of German adults.

Subjects: A total of 1763 men and 2267 women, 18- to 79-year old, who participated in the representative German National Health Interview and Examination Survey 1998 and the integrated German Nutrition Survey.

Results: The median vitamin D intake from both diet and supplements did not meet the recommended level of 5 microg/day, in either men (2.

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In the framework of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) a variety of biochemical parameters was determined in order to provide objective information on health status and particular health risks, in addition to parent interview data and anthropometric measurements. Overall 43 parameters covered three areas of particular public health interest: micronutrient deficiency, seroepidemiology of infectious diseases and immunization status, and risk indicators or risk factors for chronic non-communicable diseases. A review of available evidence regarding valid reference or cutoff values as well as the standardization of laboratory methods led to the categorization of these parameters into five classification categories.

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Iodine is an essential trace element which is found in too low quantities in the soil in Germany. The resulting iodine deficiency in human beings is countered by iodine prophylaxis, essentially consisting of iodised table salt and the iodisation of agricultural animal feed. In iodine monitoring during the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), the thyroid volumes of all children and adolescents from six years of age were determined using sonography.

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In the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) from 2003-2006 information was collected on allergic diseases (asthma, atopic dermatitis, hay fever, allergic contact eczema) from a population-based sample of 17,641 0-to 17-year-olds, and blood samples were studied for specific IgE antibodies to 20 common allergens. The lifetime prevalence (LTP) of at least one atopic disease was 22.9 % (95 % CI: 22.

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Unlabelled: From May 2003 to May 2006, the Robert Koch Institute conducted the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Nationwide data collection in 167 cities and municipalities was carried out by 4 survey teams, each consisting of a physician, centre interviewer, examiner, medical laboratory technician, environmental interviewer. Regional and seasonal factors were excluded by systematised route planning.

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The aim of the European Sero-Epidemiology Network 2 was to coordinate and standardize the serological surveillance of vaccine-preventable diseases in Europe. In this study, the standardization of hepatitis B virus (HBV) results is described. The 15 participating national laboratories tested a unique panel of 172 sera established by the Greek reference centre for HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs) and/or to the HBV core antigen (anti-HBc) by assay methods of their choice.

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The aim of this study was to investigate the seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in representative samples of the total former East German (FEG) and total former West German (FWG) populations. Type-specific testing with the HSV-1 (gG1) and HSV-2 (gG2) indirect ELISA was performed on an age- and sex-stratified random subsample of 3,792 sera collected during the 1997-1998 German National Health Survey. Weighted seroprevalence estimates were calculated for the total FEG and FWG populations.

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Objectives: To describe the seroepidemiology of herpes simplex virus (HSV) types 1 and 2 in the general populations of eight European countries to better understand recent reported changes in disease epidemiology.

Methods: Belgium, Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV-2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera.

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Objective: To analyse the association of alcohol consumption and blood lipids, haemostatic factors, and homocysteine in German adults by gender and age groups.

Design: Cross-sectional population-based survey.

Setting: Data from the German National Health Interview and Examination Survey 1998, representative for age, gender, community size, and federal state.

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The murine cytokine thymic stromal lymphopoietin (TSLP) supports the development of B220+ IgM+ immature B cells and induces thymocyte proliferation in vitro. Human TSLP, by contrast, activates CD11c+ dendritic cells, but not B or T cells. Recent studies have demonstrated that the receptor for TSLP consists of a heterodimer of the interleukin 7 (IL-7) alpha chain and a novel protein that resembles the hematopoietic cytokine receptor common gamma chain.

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In the first quarter of 2003 a National Health Survey for Children and Adolescents will be started and carried out over a period of three years. In 11,300 children and adolescents between 6 and 18 years a comprehensive iodine monitoring will be realised. The volume of the thyroid gland will be determined sonographically, thyroid hormones and the urinary iodine excretion will be measured.

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Laboratory tests will be performed as part of the National Health Survey for Children and Adolescents to identify health risks and to determine the seroprevalence of disease markers. The parameters were selected from haematology, clinical chemistry, allergology, endocrinology and serology of infectious diseases as indicators of individual health risks, to validate information collected by means of the questionnaires and to identify age specific immunity gaps of vaccine-preventable diseases.

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The prevalence of serological parameters indicative of infection with hepatitis A, B and C was determined using sera collected from representative population samples in the former East German (new) federal states and the West German (old) federal states during the German National Health and Examination Survey in 1998. Sera were tested for antibodies to hepatitis A virus (HAV), to hepatitis B core antigen (HBc) and to hepatitis B surface antigen (HBsAg), hepatitis C Virus (HCV), as well as for the presence of HBsAg and HCV-RNA. The mean weighted prevalence of anti-HAV was 46.

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Background: One of the goals of the WHO is the worldwide eradication of poliomyelitis in the next years. A high level of population immunity protects against imported wild viruses from endemic areas.

Patients And Methods: The first German Health Survey, a representative study of the health status of the population (aged between 17 and 79 years) in unified Germany, was started in 1997.

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Within the framework of the German National Health interview and Examination Survey determinations of IgG-antibodies against the bacterium Helicobacter pylori in serum samples of study participants were conducted. The prevalence for the total population of Germany was 40%. No differences could be found between sexes.

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An optimal maternal folate status reduces the risk of neural tube defects in the offspring. In the German National Health Interview and Examination Survey, red cell folate and serum folate levels have been measured in 1,266 women aged between 18 and 40 years. Applying the dietary assessment software DISHES 98 made it possible to estimate the individual folate intake.

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