Filter and export

Publications

1004 Publications visible to you, out of a total of 1004
Differential effects of enriched environment at work on cognitive decline in old age.
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

OBJECTIVES: The aim of the present study was to investigate how different mentally demanding work conditions during the professional life-i.e., enriched environments at work-might influence the rate … of cognitive decline in old age. METHODS: Individuals (n = 1,054) of the Leipzig Longitudinal Study of the Aged, a representative population-based cohort study of individuals aged 75 years and older, underwent cognitive testing via the Mini-Mental State Examination (MMSE) in up to 6 measurement waves. Type and level of mentally demanding work conditions in the participants' former professional life were classified based on the O*NET job descriptor database. RESULTS: In multivariate mixed-model analyses (controlling for sociodemographic and health-related factors), a high level of mentally demanding work tasks stimulating verbal intelligence was significantly associated with a better cognitive functioning at baseline (on average 5 MMSE points higher) as well as a lower rate of cognitive decline (on average 2 MMSE points less) over the 8-year follow-up period compared with a low level. The rate of cognitive decline in old age was also significantly lower (on average 3 MMSE points less) in individuals who had a high level of mentally demanding work tasks stimulating executive functions than those who had a low level. CONCLUSIONS: The results suggest that a professional life enriched with work tasks stimulating verbal intelligence and executive functions may help to sustain a good cognitive functioning in old age (75+ years). The findings thus emphasize that today's challenging work conditions may also promote positive health effects.

Authors: F. S. Then, T. Luck, M. Luppa, H. H. Konig, M. C. Angermeyer, S. G. Riedel-Heller

Date Published: 26th May 2015

Publication Type: Not specified

Human Diseases: dementia

Activating ERBB2/HER2 mutations indicate susceptibility to pan-HER inhibitors in Lynch and Lynch-like colorectal cancer.
GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer

Abstract (Expand)

OBJECTIVE: Microsatellite instability (MSI) is detected in approximately 15% of all colorectal cancers (CRC) and virtually in all cases with Lynch syndrome. The MSI phenotype is caused by dysfunctional … mismatch repair (MMR) and leads to accumulation of DNA replication errors. Sporadic MSI CRC often harbours BRAF(V600E); however, no consistent data exist regarding targeted treatment approaches in BRAF(wt) MSI CRC. DESIGN: Mutations and quantitative MSI were analysed by deep sequencing in 196 formalin fixed paraffin embedded (FFPE) specimens comprising Lynch and Lynch-like CRCs from the German Hereditary Nonpolyposis Colorectal Cancer registry. Functional relevance of recurrent ERBB2/HER2 mutations was investigated in CRC cell lines using reversible and irreversible HER-targeting inhibitors, EGFR-directed antibody cetuximab, HER2-directed antibody trastuzumab and siRNA-mediated ERBB2/HER2 knockdown. RESULTS: Quantification of nucleotide loss in non-coding mononucleotide repeats distinguished microsatellite status with very high accuracy (area under curve=0.9998) and demonstrated progressive losses with deeper invasion of MMR-deficient colorectal neoplasms (p=0.008). Characterisation of BRAF(wt) MSI CRC revealed hot-spot mutations in well-known oncogenic drivers, including KRAS (38.7%), PIK3CA (36.5%), and ERBB2 (15.0%). L755S and V842I substitutions in ERBB2 were highly recurrent. Functional analyses in ERBB2-mutated MSI CRC cell lines revealed a differential response to HER-targeting compounds and superiority of irreversible pan-HER inhibitors. CONCLUSIONS: We developed a high-throughput deep sequencing approach for concomitant MSI and mutational analyses in FFPE specimens. We provided novel insights into clinically relevant alterations in MSI CRC and a rationale for targeting ERBB2/HER2 mutations in Lynch and Lynch-like CRC.

Authors: M. Kloth, V. Ruesseler, C. Engel, K. Koenig, M. Peifer, E. Mariotti, H. Kuenstlinger, A. Florin, U. Rommerscheidt-Fuss, U. Koitzsch, C. Wodtke, F. Ueckeroth, S. Holzapfel, S. Aretz, P. Propping, M. Loeffler, S. Merkelbach-Bruse, M. Odenthal, N. Friedrichs, L. C. Heukamp, T. Zander, R. Buettner

Date Published: 24th May 2015

Publication Type: Not specified

Human Diseases: colorectal cancer

Long-term ovarian function in women treated with CHOP or CHOP plus etoposide for aggressive lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: Chemotherapy-associated ovarian damage comprises not only infertility, but also premature menopause. The latter has been reported as a consequence of alkylating chemotherapy for breast … cancer or Hodgkin's lymphoma. In this study, we assessed the long-term impact of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimens on ovarian function in patients with aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Long-term survivors after CHOP or CHOP plus etoposide (CHOEP) treatment within the Mabthera International Trial or the NHL-B1 trial of the German NHL Study Group were requested to respond to a questionnaire and to consent to blood sampling for hormone assessment. RESULTS: A total of 46 of 81 contacted patients with a median age of 32.5 years at the time of enrolment into the aforementioned clinical trials responded to the questionnaire. The median follow-up after completion of treatment was 14 years. Last menstrual bleeding occurred significantly earlier in patients compared with the general population (47 versus 51 years, P < 0.0001). In comparison to the distribution of menopausal symptoms in the general population, the percentage of women with moderate or severe menopausal symptoms was increased. In 23 patients who agreed to participate in laboratory analyses, anti-Muller hormone as a marker of ovarian reserve was decreased when compared with correspondent age groups of the general population. CONCLUSION: Although most female patients regain fertility after CHOP-like chemotherapy, late ovarian impairment occurs frequently. Therefore, awareness of such delayed side-effects at the time of counselling is of importance.

Authors: J. Meissner, D. Tichy, V. Katzke, T. Kuhn, S. Dietrich, T. Schmitt, M. Ziepert, E. Kuhnt, T. Rixecker, M. Zorn, M. Witzens-Harig, M. Pfreundschuh, A. D. Ho

Date Published: 13th May 2015

Publication Type: Not specified

Human Diseases: lymphoma

A recombined allele of the lipase gene CEL and its pseudogene CELP confers susceptibility to chronic pancreatitis
Genetical Statistics and Systems Biology

Abstract (Expand)

Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene. Mutations in CEL cause maturity-onset diabetes of the young as well as pancreatic exocrine dysfunction. Here we describe … a hybrid allele (CEL-HYB) originating from a crossover between CEL and its neighboring pseudogene, CELP. In a discovery series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1% (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5; 95% confidence interval (CI) = 5.1-46.9; P = 1.3 \times 10(-6) by two-tailed Fisher’s exact test). In three replication studies of nonalcoholic chronic pancreatitis, we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152) controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 \times 10(-11); formal meta-analysis). The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL-HYB in cellular models showed reduced lipolytic activity, impaired secretion, prominent intracellular accumulation and induced autophagy. These findings implicate a new pathway distinct from the protease-antiprotease system of pancreatic acinar cells in chronic pancreatitis.   Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene. Mutations in CEL cause maturity-onset diabetes of the young as well as pancreatic exocrine dysfunction. Here we describe a hybrid allele (CEL-HYB) originating from a crossover between CEL and its neighboring pseudogene, CELP. In a discovery series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1% (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5; 95% confidence interval (CI) = 5.1-46.9; P = 1.3 \times 10(-6) by two-tailed Fisher’s exact test). In three replication studies of nonalcoholic chronic pancreatitis, we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152) controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 \times 10(-11); formal meta-analysis). The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL-HYB in cellular models showed reduced lipolytic activity, impaired secretion, prominent intracellular accumulation and induced autophagy. These findings implicate a new pathway distinct from the protease-antiprotease system of pancreatic acinar cells in chronic pancreatitis.   Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene. Mutations in CEL cause maturity-onset diabetes of the young as well as pancreatic exocrine dysfunction. Here we describe a hybrid allele (CEL-HYB) originating from a crossover between CEL and its neighboring pseudogene, CELP. In a discovery series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1% (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5; 95% confidence interval (CI) = 5.1-46.9; P = 1.3 \times 10(-6) by two-tailed Fisher’s exact test). In three replication studies of nonalcoholic chronic pancreatitis, we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152) controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 \times 10(-11); formal meta-analysis). The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL-HYB in cellular models showed reduced lipolytic activity, impaired secretion, prominent intracellular accumulation and induced autophagy. These findings implicate a new pathway distinct from the protease-antiprotease system of pancreatic acinar cells in chronic pancreatitis.   Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene. Mutations in CEL cause maturity-onset diabetes of the young as well as pancreatic exocrine dysfunction. Here we describe a hybrid allele (CEL-HYB) originating from a crossover between CEL and its neighboring pseudogene, CELP. In a discovery series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1% (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5; 95% confidence interval (CI) = 5.1-46.9; P = 1.3 \times 10(-6) by two-tailed Fisher’s exact test). In three replication studies of nonalcoholic chronic pancreatitis, we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152) controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 \times 10(-11); formal meta-analysis). The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL-HYB in cellular models showed reduced lipolytic activity, impaired secretion, prominent intracellular accumulation and induced autophagy. These findings implicate a new pathway distinct from the protease-antiprotease system of pancreatic acinar cells in chronic pancreatitis. //  Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene. Mutations in CEL cause maturity-onset diabetes of the young as well as pancreatic exocrine dysfunction. Here we describe a hybrid allele (CEL-HYB) originating from a crossover between CEL and its neighboring pseudogene, CELP. In a discovery series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1% (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5; 95% confidence interval (CI) = 5.1-46.9; P = 1.3 \times 10(-6) by two-tailed Fisher’s exact test). In three replication studies of nonalcoholic chronic pancreatitis, we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152) controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 \times 10(-11); formal meta-analysis). The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL-HYB in cellular models showed reduced lipolytic activity, impaired secretion, prominent intracellular accumulation and induced autophagy. These findings implicate a new pathway distinct from the protease-antiprotease system of pancreatic acinar cells in chronic pancreatitis.

Authors: Karianne Fjeld, Frank Ulrich Weiss, Denise Lasher, Jonas Rosendahl, Jian-Min Chen, Bente B. Johansson, Holger Kirsten, Claudia Ruffert, Emmanuelle Masson, Solrun J. Steine, Peter Bugert, Miriam Cnop, Robert Grützmann, Julia Mayerle, Joachim Mössner, Monika Ringdal, Hans-Ulrich Schulz, Matthias Sendler, Peter Simon, Paweł Sztromwasser, Janniche Torsvik, Markus Scholz, Erling Tjora, Claude Férec, Heiko Witt, Markus M. Lerch, Pål R. Njølstad, Stefan Johansson, Anders Molven

Date Published: 1st May 2015

Publication Type: Journal article

Common genomic variation in the FER gene: useful to stratify patients with sepsis due to pneumonia?
LIFE - Leipzig Research Center for Civilization Diseases

Abstract

Not specified

Authors: F. Schoneweck, E. Kuhnt, M. Scholz, F. M. Brunkhorst, A. Scherag

Date Published: 30th Apr 2015

Publication Type: Not specified

Human Diseases: bacterial infectious disease, pneumonia

Age- and gender-specific norms for the German version of the Three-Factor Eating-Questionnaire (TFEQ).
LIFE Adult

Abstract (Expand)

The 'Fragebogen zum Essverhalten' (FEV) is the German version of the Three-factor-Eating-Questionnaire (TFEQ). This questionnaire covers three domains of eating behaviour ('cognitive … restraint', 'disinhibition' and 'hunger') as well as common problems (e.g. craving for sweets). So far, there is a lack of normative data of the FEV especially for the middle-aged and older population. Aim of this study therefore was to provide age- and gender-specific norms of the FEV for the general population aged 40-79 years. We studied 3144 participants of the ongoing large community-based Leipzig Research Center for Civilization Diseases (LIFE) Health Care Study. We provided age- (four age groups: 40-49, 50-59, 60-69, and 70-79 years) and gender-specific percentile ranks and T-scores for the three domains of the FEV as well as age- and gender-specific frequencies of the common problems in eating behaviour. Females scored significantly higher than males in all three domains of the FEV (p < 0.001). Older individuals showed significantly higher mean scores than the younger ones in the domain of cognitive restraint, but lower mean scores in disinhibition and hunger (p < 0.001). 45.1% of the males and 69.9% of the females reported specific problems in eating. The main problem in both genders was craving for sweets (38.6%). Eating in response to stress was mostly reported in younger individuals. The present study offers current normative data for the FEV in the middle-aged and older general population that can be applied in clinical and non-clinical settings. Information on eating behaviour can be helpful in understanding body weight modulation, and thus, may help to improve interventive and preventive programmes for overweight, obesity, and eating disorders.

Authors: A. Loffler, T. Luck, F. S. Then, M. Luppa, C. Sikorski, P. Kovacs, A. Tonjes, Y. Bottcher, J. Breitfeld, A. Horstmann, M. Loffler, C. Engel, J. Thiery, M. Stumvoll, S. G. Riedel-Heller

Date Published: 19th Apr 2015

Publication Type: Not specified

Human Diseases: obesity, eating disorder

DNA methylation array analyses identified breast cancer-associated HYAL2 methylation in peripheral blood
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Breast cancer (BC) is the leading cause of cancer-related mortality in women worldwide. Changes in DNA methylation in peripheral blood could be associated with malignancy at early stage. However, the … BC-associated DNA methylation signatures in peripheral blood were largely unknown. Here, we performed a genome-wide methylation screening and identified a BC-associated differentially methylated CpG site cg27091787 in the hyaluronoglucosaminidase 2 gene (HYAL2) (discovery round with 72 BC case and 24 controls: p = 2.61 \times 10(-9) adjusted for cell-type proportions). The substantially decreased methylation of cg27091787 in BC cases was confirmed in two validation rounds (first validation round with 338 BC case and 507 controls: p \textless 0.0001; second validation round with 189 BC case and 189 controls: p \textless 0.0001). In addition to cg27091787, the decreased methylation of a 650-bp CpG island shore of HYAL2 was also associated with increased risk of BC. Moreover, the expression and methylation of HYAL2 were inversely correlated with a p-value of 0.006. To note, the BC-associated decreased HYAL2 methylation was replicated in the T-cell fraction (p = 0.034). The cg27091787 methylation level enabled a powerful discrimination of early-stage BC cases (stages 0 and I) from healthy controls [area under curve (AUC) = 0.89], and was robust for the detection of BC in younger women as well (age \textless 50, AUC = 0.87). Our study reveals a strong association between decreased HYAL2 methylation in peripheral blood and BC, and provides a promising blood-based marker for the detection of early BC.

Authors: Rongxi Yang, Katrin Pfütze, Manuela Zucknick, Christian Sutter, Barbara Wappenschmidt, Frederik Marme, Bin Qu, Katarina Cuk, Christoph Engel, Sarah Schott, Andreas Schneeweiss, Hermann Brenner, Rainer Claus, Christoph Plass, Peter Bugert, Markus Hoth, Christof Sohn, Rita Schmutzler, Claus R. Bartram, Barbara Burwinkel

Date Published: 15th Apr 2015

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Navigate

Health Atlas - Local Data Hub/Leipzig

The Health Atlas - Local Data Hub/Leipzig is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields.

Registered Repository

re3data.org Badge
Powered by
 (v.1.13.0-master)
Health Atlas | Funding and Programmes | Credits | Terms & Conditions | Privacy Policy | Imprint
Copyright © 2008 - 2021 The University of Manchester and HITS gGmbH
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

By continuing to use this site you agree to the use of cookies