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Biomedical subjects

U Schweizer

Publications and source records attributed to U Schweizer.

8 recordsLinked to original sources
PubMed2004

Selenium and selenoproteins in mammals: extraordinary, essential, enigmatic.

Selenium (Se), once known only for its potential toxicity, is now well established as an essential trace element for mammals. Insufficient Se intake predisposes to and manifests in a variety of diseases. Recent studies have proven that it is the synthesis of selenocysteine (Sec)-containing proteins, designated selenoproteins, which represents an essential prerequisite for regular development and a long and healthy life. New transgenic mouse models analysing those selenoproteins with proven enzymatic functions displayed particular phenotypes and highlighted essential Se-dependent processes in development, growth or against specific challenges. While there is a growing molecular understanding of and general agreement on the importance of sufficiently high Se intake and undisturbed selenoprotein biosynthesis, many of the recently identified selenoproteins are still uncharacterised, and the effects and consequences of supra-physiological Se dosages are not biochemically understood. With the recent definition of the human and mouse selenoproteomes and a growing number of available tools, the Se field is now geared for a great leap forward. Se biology has already broadened our knowledge about the genetic code and about protein translation. It now holds great promises also for a better understanding of some key aspects of cancer, inflammation, fertility and prevention of age-associated diseases.

Animals↗
PubMed2000

Developmental motoneuron cell death and neurotrophic factors.

During the development of higher vertebrates, motoneurons are generated in excess. In the lumbar spinal cord of the developing rat, about 6000 motoneurons are present at embryonic day 14. These neurons grow out axons which make contact with their target tissue, the skeletal muscle, and about 50% of the motoneurons are lost during a critical period from embryonic day 14 until postnatal day 3. This process, which is called physiological motoneuron cell death, has been the focus of research aiming to identify neurotrophic factors which regulate motoneuron survival during this developmental period. Motoneuron cell death can also be observed in vitro when the motoneurons are isolated from the embryonic avian or rodent spinal cord. These isolated motoneurons and other types of primary neurons have been a useful tool for studying basic mechanisms underlying neuronal degeneration during development and under pathophysiological conditions in neurodegenerative disorders. Accumulating evidence from such studies suggests that some specific requirements of motoneurons for survival and proper function may change during development. The focus of this review is a synopsis of recent data on such specific mechanisms.

Animals↗
PubMed1999

Photocrosslinking locates a binding site for the large subunit of human replication protein A to the damaged strand of cisplatin-modified DNA.

The repair proteins XPA, XPC and replication protein A (RPA) have been implicated in the primary recognition of damaged DNA sites during nucleotide excision repair. Detailed structural information on the binding of these proteins to DNA lesions is however lacking. We have studied the binding of human RPA (hRPA) and hRPA-XPA-complexes to model oligonucleo-tides containing a single 1, 3-d(GTG)-cisplatin-modification by photocrosslinking and electrophoretic mobility shift experiments. The 70 kDa subunit of hRPA can be crosslinked with high efficiency to cisplatin-modified DNA probes carrying 5-iodo-2"-deoxyuridin (5-IdU) as crosslinking chromophore. High efficiency crosslinking is dependent on the presence of the DNA lesion and occurs preferentially at its 5"-side. Examination of the crosslinking efficiency in dependence on the position of the 5-IdU chromophore indicates a specific positioning of hRPA with respect to the platination site. When hRPA and XPA are both present mainly hRPA is crosslinked to the DNA. Our mobility shift experiments directly show the formation of a stable ternary complex of hRPA, XPA and the damaged DNA. The affinity of the XPA-hRPA complex to the damaged DNA is increased by more than one order of magnitude as compared to hRPA alone.

Antibodies, Monoclonal↗
PubMed1999

TNF-alpha pretreatment prevents subsequent activation of cultured brain cells with TNF-alpha and hypoxia via ceramide.

We have developed a cellular model in which cultured astrocytes and brain capillary endothelial cells preconditioned with tumor necrosis factor-alpha (TNF-alpha) fail to upregulate intercellular adhesion molecule-1 (ICAM-1) protein (80% inhibition) and mRNA (30% inhibition) when challenged with TNF-alpha or exposed to hypoxia. Inasmuch as ceramide is known to mediate some of the effects of TNF-alpha, its levels were measured at various times after the TNF-alpha preconditioning. We present evidence for the first time that, in normal brain cells, TNF-alpha pretreatment causes a biphasic increase of ceramide levels: an early peak at 15-20 min, when ceramide levels increased 1.9-fold in astrocytes and 2.7-fold in rat brain capillary endothelial cells, and a delayed 2- to 3-fold ceramide increase that occurs 18-24 h after addition of TNF-alpha. The following findings indicate that the delayed ceramide accumulation results in cell unresponsiveness to TNF-alpha: 1) coincident timing of the ceramide peak and the tolerance period, 2) mimicking of preconditioning by addition of exogenous ceramide, and 3) attenuation of preconditioning by fumonisin B1, an inhibitor of ceramide synthesis. In contrast to observations in transformed cell lines, the delayed ceramide increase was transient and did not induce apoptosis in brain cells.

Animals↗
PubMed1996

Endogenous fertility and the Henry George Theorem.

"Models of endogenous demographic change deal with population size as an additional object of the welfare analysis. In these models the overlapping-generations (OLG) model serves as the basic framework. In club theory, too, population size is treated as an endogenous variable. In local public goods (LPG) models, the so-called Henry George Theorem, which requires local public expenditures to be financed by a 100% tax on aggregate land rent, is known as a (first-order) condition for club efficiency. The present paper establishes and exploits an isomorphism between steady states of the OLG model and allocations of the LPG model. The paper revisits Samuelson's fallacy concerning his goldenest golden rule and it explores institutional arrangements that sustain the optimum growth of population."

Demography↗
PubMed1991

Cell volume is a major determinant of proteolysis control in liver.

Hepatic proteolysis is inhibited by insulin, amino acids and hypoosmotic cell swelling and is stimulated by glucagon. These effectors simultaneously modulate cell volume in the intact liver, as shown by measurements of the intracellular water space. A close relationship exists between the effect on proteolysis and the accompanying cell volume change, regardless of whether hepatic proteolysis was modified by insulin, glucagon, cyclic AMP, glutamine, glycine, barium of hypoosmotic exposure. It is suggested that cell volume changes exerted by hormones and amino acids play a crucial role in the regulation of hepatic proteolysis.

Animals↗
PubMed1986

Spatial dynamics and metropolitan change.

"This special issue presents contributions to a collaborative effort to analyze 'the dynamics of metropolitan processes and policies'....[It] contains four papers which focus on industrial change and economic restructuring; two papers deal with population relocation and migration processes; one paper contains a study of economic cycles in space and one paper treats the assessment of urban investment and urban renewal projects." The geographic focus is on the developed countries.

Demography↗