University of Basel

About: University of Basel is a education organization based out in Basel, Basel-Stadt, Switzerland. It is known for research contribution in the topics: Population & Transplantation. The organization has 25084 authors who have published 52975 publications receiving 2388002 citations. The organization is also known as: Universität Basel & Basel University.

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy

Abstract: Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.

Novel mechanisms and functions of complement

Abstract: Progress at the beginning of the 21st century transformed the perception of complement from that of a blood-based antimicrobial system to that of a global regulator of immunity and tissue homeostasis. More recent years have witnessed remarkable advances in structure-function insights and understanding of the mechanisms and locations of complement activation, which have added new layers of complexity to the biology of complement. This complexity is readily reflected by the multifaceted and contextual involvement of complement-driven networks in a wide range of inflammatory and neurodegenerative disorders and cancer. This Review provides an updated view of new and previously unanticipated functions of complement and how these affect immunity and disease pathogenesis.

Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis.

Abstract: BACKGROUND: It was investigated whether the European Group for Blood and Marrow Transplantation risk score, previously established for chronic myeloid leukemia, could be used to predict outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological disease in general. METHODS: Age of patient, disease stage, time interval from diagnosis to transplant, donor type, and donor-recipient sex combination were used to establish a score from 0 to 7 points. Its validity was tested in 56,505 patients, 33,113 (58%) male, 23,392 female, median age 33 years (range, 0.5-77 years), with an allogeneic HSCT for a hematological disorder between 1980 and 2005. RESULTS: Survival probability at 5 years decreased from 71% (95% confidence interval [CI], 69%-73%) for risk score 0 for the whole cohort (75%, 95% CI, 72%-78% for the most recent time cohort) to 24% (95% CI, 21%-27% for risk score 6 and 7; 25%, 95% CI, 22%-29% most recent cohort). Transplant-related mortality increased from 15% (95% CI, 14%-17%) for risk score 0 (11%, 95% CI, 9%-13%, most recent cohort) to 47% with risk score 6 and 7 (95% CI, 44%-50%) for the whole cohort (45%, 95% CI, 42%-48%, most recent cohort). The risk score was predictive in all disease categories, over all time periods, and was not altered by transplant techniques. CONCLUSIONS: Five well-defined pretransplant patient and donor characteristics give a reasonable risk estimate of allogeneic HSCT. This risk score can provide a basis for the decision between transplant and nontransplant strategies.

Brain aging and neurodegeneration: from a mitochondrial point of view.

Abstract: Aging is defined as a progressive time-related accumulation of changes responsible for or at least involved in the increased susceptibility to disease and death. The brain seems to be particularly sensitive to the aging process since the appearance of neurodegenerative diseases, including Alzheimer's disease, is exponential with the increasing age. Mitochondria were placed at the center of the 'free-radical theory of aging', because these paramount organelles are not only the main producers of energy in the cells, but also to main source of reactive oxygen species. Thus, in this review, we aim to look at brain aging processes from a mitochondrial point of view by asking: (i) What happens to brain mitochondrial bioenergetics and dynamics during aging? (ii) Why is the brain so sensitive to the age-related mitochondrial impairments? (iii) Is there a sex difference in the age-induced mitochondrial dysfunction? Understanding mitochondrial physiology in the context of brain aging may help identify therapeutic targets against neurodegeneration. This article is part of a series "Beyond Amyloid".

Prognostic relevance of gene amplifications and coamplifications in breast cancer.

Abstract: Multiple different oncogenes have been described previously to be amplified in breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability. As such, presence of one or several gene amplifications may have prognostic significance. To assess the prognostic importance of amplifications and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow-up information. Fluorescence in situ hybridizations revealed amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and EGFR in 0.8% of the tumors. All gene amplifications were significantly associated with high grade. HER2 (P < 0.001) and MYC amplification (P < 0.001) were also linked to shortened survival. In case of HER2, this was independent of grade, pT, and pN categories. MYC amplification was almost 3 times more frequent in medullary cancer (15.9%), than in the histologic subtype with the second highest frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated with estrogen receptor/progesterone receptor negativity (P < 0.001) whereas CCND1 amplification was linked to estrogen receptor/progesterone receptor positivity (P < 0.001). Coamplifications were more prevalent than expected based on the individual frequencies. Coamplifications of one or several other oncogenes occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than tumors with only one of these amplifications. Furthermore, a gradual decrease of survival was observed with increasing number of amplifications. In conclusion, these data support a major prognostic impact of genomic instability as determined by a broad gene amplification survey in breast cancer.