University of Düsseldorf

About: University of Düsseldorf is a education organization based out in Düsseldorf, Germany. It is known for research contribution in the topics: Population & Diabetes mellitus. The organization has 25225 authors who have published 49155 publications receiving 1946434 citations.

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

Abstract: Histamine is a developmentally highly conserved autacoid found in most vertebrate tissues. Its physiological functions are mediated by four 7-transmembrane G protein–coupled receptors (H1R, H2R, H3R, H4R) that are all targets of pharmacological intervention. The receptors display molecular heterogeneity and constitutive activity. H1R antagonists are long known antiallergic and sedating drugs, whereas the H2R was identified in the 1970s and led to the development of H2R-antagonists that revolutionized stomach ulcer treatment. The crystal structure of ligand-bound H1R has rendered it possible to design new ligands with novel properties. The H3R is an autoreceptor and heteroreceptor providing negative feedback on histaminergic and inhibition on other neurons. A block of these actions promotes waking. The H4R occurs on immuncompetent cells and the development of anti-inflammatory drugs is anticipated.

AD dementia risk in late MCI, in early MCI, and in subjective memory impairment

Abstract: Objective To compare the risk of developing Alzheimer's disease (AD) dementia in late mild cognitive impairment (LMCI), early MCI (EMCI), and subjective memory impairment (SMI) with normal test performance. Methods The baseline sample (n = 2892) of the prospective cohort study in nondemented individuals (German Study on Aging, Cognition and Dementia in Primary Care Patients) was divided into LMCI, EMCI, SMI, and control subjects by delayed recall performance. These groups were subdivided by the presence of self-reported concerns associated with experienced memory impairment. AD dementia risk was assessed over 6 years. Results Across all groups, risk of AD dementia was greatest in LMCI. In those with self-reported concerns regarding their memory impairment, SMI and EMCI were associated with a similarly increased risk of AD dementia. In those subgroups without concerns, SMI was not associated with increased risk of AD dementia, but EMCI remained an at-risk condition. Conclusions SMI and EMCI with self-reported concerns were associated with the same risk of AD dementia, suggesting that pre-LMCI risk conditions should be extended to SMI with concerns.

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

Abstract: The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases.