A new generation of radiofluorinated pyrimidine-2,4,6-triones as MMP-targeted radiotracers for positron emission tomography.

Radiolabeled C-5-disubstituted pyrimidine-2,4,6-triones have recently been suggested by our group as a class of potent matrix metalloproteinase (MMP) targeted radiotracers that can noninvasively visualize activated MMPs by means of positron emission tomography (PET). MMPs belong to the zinc- and calcium-dependent endopeptidases which are involved in the proteolytic degradation of components of the extracellular matrix (ECM) but also are capable of processing and releasing bioactive molecules such as growth factors, proteinase inhibitors, and cytokines. Locally increased levels of activated MMPs modulate and contribute to the progression of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others.

A role for seipin in lipid droplet dynamics and inheritance in yeast.

Malfunctions of processes involved in cellular lipid storage and mobilization induce the pathogenesis of prevalent human diseases such as obesity, type 2 diabetes and atherosclerosis. Lipid droplets are the main lipid storage depots for neutral lipids in eukaryotic cells, and as such fulfil an essential function to balance cellular lipid metabolism and energy homeostasis. Despite significant progress in identifying key metabolic enzymes involved in lipid storage and their regulation in various model organisms, some fundamental questions as to the biogenesis, subcellular distribution and inheritance of lipid droplets are as yet unsolved.

The role for decorin in delayed-type hypersensitivity.

Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling, and cell growth. Because decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity [DTH]) in decorin-deficient (Dcn(-/-)) and wild-type mice. Dcn(-/-) mice showed a reduced ear swelling 24 h after oxazolone treatment with a concurrent attenuation of leukocyte infiltration.

Analysis of particle strain in stirred bioreactors by drop breakage investigations.

Understanding of particle strain and drop breakage is relevant for various technical applications. To analyze it, single drop experiments in a breakage cell and evolving drop size distributions in an agitated system are studied. The mechanisms for particle strain and drop breakage are assumed to be comparable for the investigated turbulent flow regime.

The association of education with body mass index and waist circumference in the EPIC-PANACEA study.

Background: To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Method: This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables.

The impact of social status inconsistency on cardiovascular risk factors, myocardial infarction and stroke in the EPIC-Heidelberg cohort.

Background: Social inequalities in cardiovascular diseases are well documented. Yet, the relation of social status inconsistency (having different ranks in two or more status indicators like education, occupational position or income) and medical conditions of heart or vessels is not clear. Status inconsistency (SI) is assumed to be stressful, and the association of psychosocial distress and health is well known.

Development and evaluation of endothelin-A receptor (radio)ligands for positron emission tomography.

The expression and function of endothelin (ET) receptors are abnormal in cardiovascular diseases, tumor progression, and tumor metastasis. A previously reported promising radioligand for positron emission tomography (PET) based on the non-peptide ET(A) receptor antagonist PD 156707 showed specific binding to target receptors in the myocardium but high accumulation in bile and intestine, probably because of its high lipophilicity. In this study we describe the synthesis of a series of fluorinated derivatives with hydrophilic building blocks.

The contribution of risk factors to the higher incidence of invasive and in situ breast cancers in women with higher levels of education in the European prospective investigation into cancer and nutrition.

The authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasive breast cancer. Reproductive history (age at first full-term pregnancy and parity), exposure to endogenous and exogenous hormones, height, and health behaviors were accounted for in the analyses.

Simultaneously accounting for population structure, genotype by environment interaction, and spatial variation in marker-trait associations in sugarcane.

Few association mapping studies have simultaneously accounted for population structure, genotype by environment interaction (GEI), and spatial variation. In this sugarcane association mapping study we tested models accounting for these factors and identified the impact that each model component had on the list of markers declared as being significantly associated with traits. About 480 genotypes were evaluated for cane yield and sugar content at three sites and scored with DArT markers.

Cellular organization of adult neurogenesis in the Common Marmoset.

Adult neurogenesis within the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricle (LV) has been most intensely studied within the brains of rodents such as mice and rats. However, little is known about the cell types and processes involved in adult neurogenesis within primates such as the common marmoset (Callithrix jacchus). Moreover, substantial differences seem to exist between the neurogenic niche of the LV between rodents and humans.

Eating out, weight and weight gain. A cross-sectional and prospective analysis in the context of the EPIC-PANACEA study.

Objective: The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Subjects: This study included a representative sample of 24,310 randomly selected EPIC participants.

Methods: Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000.

Isochronous assessment of cardiac metabolism and function in mice using hybrid PET/MRI.

Unlabelled: Recently, integrated small-animal PET/MRI prototypes that provide isochronous and coregistered datasets of morphology and function through the simultaneous acquisition of PET and MRI data have been developed. However, the need for MRI compatibility can constrain the technical design of the PET components and may lead to a lower sensitivity and lower spatial and temporal resolutions. The aim of this study was to evaluate the suitability of a prototype preclinical PET/MRI system for the simultaneous assessment of cardiac metabolism and function in mice.

Meat consumption and prospective weight change in participants of the EPIC-PANACEA study.

Background: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results.

Objective: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project.

Matrix-metalloproteinases as imaging targets for inflammatory activity in atherosclerotic plaques.

Cardiovascular events such as myocardial infarction or stroke resulting from atherosclerosis still account for the majority of deaths worldwide. New imaging approaches focusing on the visualization of inflammation in the vessel wall may emerge as tools for individualized risk assessment and prevention of events. Enzymes such as matrix-metalloproteinases (MMPs) are involved in several steps in plaque progression driving plaques into vulnerable, rupture-prone states.

Radiofluorinated pyrimidine-2,4,6-triones as molecular probes for noninvasive MMP-targeted imaging.

Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endopeptidases. Representing a subfamily of the metzincin superfamily, MMPs are involved in the proteolytic degradation of components of the extracellular matrix. Unregulated MMP expression, MMP dysregulation and locally increased MMP activity are common features of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others.

Autonomic modulation and antiarrhythmic therapy in a model of long QT syndrome type 3.

Aims: Clinical observations in patients with long QT syndrome carrying sodium channel mutations (LQT3) suggest that bradycardia caused by parasympathetic stimulation may provoke torsades de pointes (TdP). Beta-adrenoceptor blockers appear less effective in LQT3 than in other forms of the disease.

Methods And Results: We studied effects of autonomic modulation on arrhythmias in vivo and in vitro and quantified sympathetic innervation by autoradiography in heterozygous mice with a knock-in deletion (DeltaKPQ) in the Scn5a gene coding for the cardiac sodium channel and increased late sodium current (LQT3 mice).

Management of intramedullary spinal cord lesions: interdependence of the longitudinal extension of the lesion and the functional outcome.

To evaluate the impact of the longitudinal extension of intramedullary lesions on the neurological status and postoperative outcome. Forty-six patients operated in our Department between February 2004 and June 2007 have been included in this study. The patients were classified in two groups according to the longitudinal extension of the lesion over less than three vertebral segments (group A) and over exactly three or more vertebral segments (group B).

NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits.

To date, long-term consequences of septic encephalopathy on cerebral metabolism, cognition, learning, and memory capabilities and factors involved are poorly understood. In this study, we used a murine sepsis model to demonstrate that bacterial lipopolysaccharide (LPS) causes long-term cognitive deficits in mice. Two months after LPS treatment, wild-type mice committed more working and reference memory errors than controls.

Multimodal vessel visualization of mouse aorta PET/CT scans.

In this paper, we present a visualization system for the visual analysis of PET/CT scans of aortic arches of mice. The system has been designed in close collaboration between researchers from the areas of visualization and molecular imaging with the objective to get deeper insights into the structural and molecular processes which take place during plaque development. Understanding the development of plaques might lead to a better and earlier diagnosis of cardiovascular diseases, which are still the main cause of death in the western world.

Occupational exposures contribute to educational inequalities in lung cancer incidence among men: Evidence from the EPIC prospective cohort study.

The aim of this study is to investigate to what extent occupational exposures may explain socioeconomic inequalities in lung cancer incidence after adjusting for smoking and dietary factors. Analyses were based on a subsample of the European Prospective Investigation into Cancer and Nutrition (EPIC study), a prospective cohort. The analyses included 703 incident lung cancer cases among men in Denmark, the United Kingdom, Germany, Italy, Spain and Greece.

Molecular imaging of apoptosis in vivo with scintigraphic and optical biomarkers--a status report.

The balance between proliferation and programmed cell death--apoptosis--is essential for multicellular organisms which use apoptosis to regulate and maintain the number and type of their cells during embryogenesis, growth and homeostasis. Increased cell proliferation or enhanced cell loss can be caused by dysregulated apoptosis and are observed in various diseases: in clinical scenarios such as neurodegenerative disorders, myocardial infarction and stroke the rate of apoptosis is upregulated compared to the physiological situation, while in clinical scenarios such as cancer or autoimmune diseases which are connected with pathological proliferation, apoptosis is often downregulated. Therefore, non-invasive imaging of apoptosis is of great clinical interest as patients would clearly benefit from the diagnosis of cell loss post infarction or from monitoring apoptosis triggered by chemotherapy or radiation therapy of tumours.

Level of education and the risk of lymphoma in the European prospective investigation into cancer and nutrition.

Introduction: Lymphomas belong to the few cancer sites with increasing incidence over past decades, and only a few risk factors have been established. We explored the association between education and the incidence of lymphoma in the prospective EPIC study.

Materials And Methods: Within 3,567,410 person-years of follow-up, 1,319 lymphoma cases [1,253 non-Hodgkin lymphomas (NHL) and 66 Hodgkin lymphomas (HL)] were identified.