Institution
University of Kiel
Education•Kiel, Germany•
About: University of Kiel is a education organization based out in Kiel, Germany. It is known for research contribution in the topics: Population & Crystal structure. The organization has 27816 authors who have published 57114 publications receiving 2061802 citations. The organization is also known as: Christian Albrechts University & Christian-Albrechts-Universität zu Kiel.
Topics: Population, Crystal structure, Transplantation, Gene, Receptor
Papers published on a yearly basis
Papers
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TL;DR: The identification of a specific NF-κB promoter module activated in the inflammatory stress response of progressive DN has helped to characterize upstream pathways as potential targets for the treatment of progressive renal diseases such as DN.
Abstract: Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and a major risk factor for cardiovascular mortality in diabetic patients. To evaluate the multiple pathogenetic factors implicated in DN, unbiased mRNA expression screening of tubulointerstitial compartments of human renal biopsies was combined with hypothesis-driven pathway analysis. Expression fingerprints obtained from biopsies with histological diagnosis of DN ( n = 13) and from control subjects (pretransplant kidney donors [ n = 7] and minimal change disease [ n = 4]) allowed us to segregate the biopsies by disease state and stage by the specific expression signatures. Functional categorization showed regulation of genes linked to inflammation in progressive DN. Pathway mapping of nuclear factor-κB (NF-κB), a master transcriptional switch in inflammation, segregated progressive from mild DN and control subjects by showing upregulation of 54 of 138 known NF-κB targets. The promoter regions of regulated NF-κB targets were analyzed using ModelInspector, and the NF-κB module NFKB\_IRFF\_01 was found to be specifically enriched in progressive disease. Using this module, the induction of eight NFKB\_IRFF\_01–dependant genes was correctly predicted in progressive DN ( B2M , CCL5/RANTES , CXCL10/IP10 , EDN1 , HLA-A , HLA-B , IFNB1 , and VCAM1 ). The identification of a specific NF-κB promoter module activated in the inflammatory stress response of progressive DN has helped to characterize upstream pathways as potential targets for the treatment of progressive renal diseases such as DN.
380 citations
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TL;DR: This study highlights the need to understand more fully the rationale behind the continued support for continued research into congenital melanocytic naevi atypical malignant melanoma.
Abstract: Summary
Background The risk of malignant melanoma in congenital melanocytic naevi (CMN) is a matter of controversial and ongoing debate.
Objectives The purpose of this systematic review is to provide a careful and detailed summary of the published data, including several recently published studies.
Methods Articles on CMN (n = 1424) were retrieved from Medline, 1966–October 2005. Case reports and studies lacking relevant clinical information were excluded. Only systematic collections of cases were taken into consideration. Series with fewer than 20 patients or studies with a mean follow-up of <3 years were regarded as epidemiologically less significant.
Results Fourteen articles were finally chosen for further analysis. The studies varied significantly with respect to study design (source of cases; retrospective vs. prospective analysis), age of patients, follow-up time, and naevus characteristics. The frequency of melanomas ranged between 0·05% and 10·7% and was significantly higher in smaller studies (P < 0·0001). In a total of 6571 patients with CMN who were followed for a mean of 3·4–23·7 years, 46 patients (0·7%) developed 49 melanomas. The mean age at diagnosis of melanoma was 15·5 years (median 7). By comparison with age-adjusted data from the Surveillance, Epidemiology and End Results database, we calculated that patients with CMN carry an approximately 465-fold increased relative risk of developing melanoma during childhood and adolescence. Primary melanomas arose inside the naevi in 33 of 49 cases (67%). In seven cases (14%), metastatic melanoma with unknown primary was encountered; in four cases (8%) the melanoma developed at an extracutaneous site. The risk of developing melanoma and the rate of fatal courses were by far highest in CMN ≥40 cm in diameter.
Conclusions The overall risk of melanoma of 0·7% in all 14 studies was lower than expected. The higher incidence of melanomas in smaller studies indicates selection bias. The melanoma risk strongly depends on the size of CMN and is highest in those naevi traditionally designated as garment naevi. The median age of 7 years at diagnosis of melanoma points to a risk maximum in childhood and adolescence. Future studies on CMN should report: (i) diameter, percentage of body surface, and localization of the CMN; (ii) percentage of naevus area removed by excision or subject to dermabrasion or other superficial treatments; (iii) mean and median age at entry into the study; (iv) mean and median follow-up time; (v) details on each melanoma case; (vi) standardized morbidity ratio of melanoma; and (vii) percentage of neurocutaneous melanosis.
379 citations
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TL;DR: In this paper, the major and trace element and Sr-Nd-Pb-O-C isotopic compositions are presented for carbonatites from the Cape Verde (Brava, Fogo, Sao Tiago, Maio and Sao Vicente) and Canary (Fuerteventura) Islands.
Abstract: Major and trace element and Sr–Nd–Pb–O–C isotopic compositions are presented for carbonatites from the Cape Verde (Brava, Fogo, Sao Tiago, Maio and Sao Vicente) and Canary (Fuerteventura) Islands. Carbonatites show pronounced enrichment in Ba, Th, REE, Sr and Pb in comparison to most silicate volcanic rocks and relative depletion in Ti, Zr, Hf, K and Rb. Calcio (calcitic)-carbonatites have primary (mantle-like) stable isotopic compositions and radiogenic isotopic compositions similar to HIMU-type ocean island basalts. Cape Verde carbonatites, however, have more radiogenic Pb isotope ratios (e.g. 206Pb/204Pb=19.3–20.4) than reported for silicate volcanic rocks from these islands (18.7–19.9; Gerlach et al. 1988; Kokfelt 1998). We interpret calcio-carbonatites to be derived from the melting of recycled carbonated oceanic crust (eclogite) with a recycling age of ~1.6 Ga. Because of the degree of recrystallization, replacement of calcite by secondary dolomite and elevated ∂13C and ∂18O, the major and trace element compositions of the magnesio (dolomitic)-carbonatites are likely to reflect secondary processes. Compared with Cape Verde calcio-carbonatites, the less radiogenic Nd and Pb isotopic ratios and the negative Δ7/4 of the magnesio-carbonatites (also observed in silicate volcanic rocks from the Canary and Cape Verde Islands) cannot be explained through secondary processes or through the assimilation of Cape Verde crust. These isotopic characteristics require the involvement of a mantle component that has thus far only been found in the Smoky Butte lamproites from Montana, which are believed to be derived from subcontinental lithospheric sources. Continental carbonatites show much greater variation in radiogenic isotopic composition than oceanic carbonatites, requiring a HIMU-like component similar to that observed in the oceanic carbonatites and enriched components. We interpret the enriched components to be Phanerozoic through Proterozoic marine carbonate (e.g. limestone) recycled through shallow, subcontinental–lithospheric–mantle and deep, lower-mantle sources.
378 citations
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QIMR Berghofer Medical Research Institute1, University Medical Center Groningen2, University of Kiel3, Charité4, Max Delbrück Center for Molecular Medicine5, University of California, San Francisco6, University of Amsterdam7, Karolinska Institutet8, University of Bristol9, Norwegian University of Science and Technology10, University of Melbourne11, Stanford University12, University of Michigan13, Greifswald University Hospital14, University of Greifswald15, Harry Perkins Institute of Medical Research16, University Hospital Bonn17, Ludwig Maximilian University of Munich18, Kaiser Permanente19, VU University Medical Center20, Karolinska University Hospital21, GlaxoSmithKline22
TL;DR: A genome-wide association study of a broad allergic disease phenotype that considers the presence of any one of these three diseases identified 136 independent risk variants, including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology.
Abstract: Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.
378 citations
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TL;DR: It can be expected that future diagnostic algorithms will include molecular parameters to detect early disease or guide therapies by predicting the individual course of disease.
378 citations
Authors
Showing all 28103 results
Name | H-index | Papers | Citations |
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Stefan Schreiber | 178 | 1233 | 138528 |
Jun Wang | 166 | 1093 | 141621 |
William J. Sandborn | 162 | 1317 | 108564 |
Jens Nielsen | 149 | 1752 | 104005 |
Tak W. Mak | 148 | 807 | 94871 |
Annette Peters | 138 | 1114 | 101640 |
Severine Vermeire | 134 | 1086 | 76352 |
Peter M. Rothwell | 134 | 779 | 67382 |
Dusan Bruncko | 132 | 1042 | 84709 |
Gideon Bella | 129 | 1301 | 87905 |
Dirk Schadendorf | 127 | 1017 | 105777 |
Neal L. Benowitz | 126 | 792 | 60658 |
Thomas Schwarz | 123 | 701 | 54560 |
Meletios A. Dimopoulos | 122 | 1371 | 71871 |
Christian Weber | 122 | 776 | 53842 |