Biomedical subjects

Peter Van Osta

Publications and source records attributed to Peter Van Osta.

3 recordsLinked to original sources

PubMed2006

Cytomics and drug discovery.

Pharmaceutical companies try to develop new drugs that have a high success rate of reaching the market. However, current disease models lack a strong correlation to clinical reality, because of the underestimation of the complexity and variability of clinical disease processes. This leads to high attrition rates late in drug development and soaring costs. Improvement of disease models is an important issue to reduce the high attrition rates in drug development. Using cell-based disease models, which should take into account the molecular diversity of the human cytome, will improve the predictive value of drug discovery.

Biomedical Research↗

PubMed2006

Extracting quantitative information from tissue--an industrial perspective.

The focus of this article is to provide an overview of the current technologies for the pharmaceutical and biotech industry. Disease processes express themselves in the functional and structural disturbance of cellular systems. Cells and their metabolites constitute the building blocks of tissues and entire organisms. Studying the spatial and temporal phenotype of disease processes in tissues at the cellular level reveals a multitude of information about the progress and status of a disease. Detailed exploration of tissues by slide-based cytometry is an important source of information about disease processes. Technological and analytical advances allow us to shed a new light on tissues and to come to a better understanding of the complexity of disease processes. Dealing with complex multidimensional datasets from tissue samples requires an advanced approach to image processing and data management. The increase in computing power and the continuing research into imaging algorithms allow us to improve the exploration of the data content of tissues.

Animals↗

PubMed2002

In vitro studies of Flemish, Dutch, and wild-type beta-amyloid provide evidence for two-staged neurotoxicity.

Mutations in the beta-amyloid (Abeta) sequence of the amyloid precursor protein gene (APP) present with variable disease phenotypes. While patients with the Dutch APP mutation (E693Q) have predominantly hemorrhagic strokes, Flemish APP (A692G) patients develop both strokes and Alzheimer's disease (AD). To determine whether these diverse clinical and pathological presentations are due to mutant Abeta or APP, we studied the effect of Flemish, Dutch, and wild-type Abeta/APP on phosphorylation of specific tau epitopes observed in AD. No effect was observed in differentiated SH-SY5Y cells either stably expressing APP or treated with synthetic Abeta(12-42). However, we did observe a paradoxical temporal difference in the neurotoxic potential of mutant and wild-type Abeta. While long 24-h incubation at physiological levels of Abeta (2 microM) showed a higher amount of apoptosis for Dutch Abeta, a short 2-h incubation showed elevated apoptosis for Flemish and wild-type Abeta. The altered aggregating properties of Abeta, with Dutch Abeta aggregating faster and Flemish Abeta slower than wild type, elucidated a discrete two-phase Abeta neurotoxicity. We propose here that, at least in vitro, Abeta might be neurotoxic in an initial phase due to its soluble oligomeric or other early toxic Abeta intermediate(s), which is perhaps distinct from the late neurotoxicity incurred by aggregated larger assemblies of Abeta.

Alzheimer Disease↗