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Biomedical subjects

C Wüthrich

Publications and source records attributed to C Wüthrich.

8 recordsLinked to original sources
PubMed2004

Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury?

OBJECTIVE: To investigate glutathione and amino acids related to glutathione metabolism in patients with anorexia nervosa in order to test the hypothesis that these patients exhibit a deficiency of glutathione and therefore might be at an increased risk of developing toxic liver injury. DESIGN: Controlled observatory study and case report. SETTING: University Hospital. SUBJECTS: Subjects included 11 female patients with anorexia nervosa and 12 healthy female controls. INTERVENTIONS: Determination of fasting free and total glutathione, homocysteine, vitamins B(6) and B(12) and folic acid in plasma. RESULTS: A 14-y-old patient with a body mass index of 12.6 kg/m(2) presented with markedly elevated transaminases (ALAT >50 x upper limit of normal), and paracetamol was detected in her blood. Patients with anorexia nervosa exhibited lower circulating concentrations of free cysteine (8.9+/-1.5 vs 12.0+/-1.4 micromol/l) and free and total glutathione (5.0+/-1.3 vs 7.1+/-1.2 and 11.2+/-3.8 vs 16.2+/-5.0 micromol/l, respectively). The plasma concentrations of homocysteine (17.5+/-4.9 vs 12.0+/-3.8 micromol/l) and also of glycine (194+/-37 vs 143+/-41 micromol/l) and glutamine (422+/-51 vs 353+/-51 micromol/l) were significantly higher in patients with anorexia nervosa who were not deficient in folic acid, vitamin B(6) and B(12). CONCLUSIONS: Lower plasma concentrations of glutathione suggest lower intracellular concentrations of the tripeptide. Higher homocysteine, glycine and glutamine concentrations point to a decreased utilization of these amino acids for glutathione synthesis and an impairment of trans-sulfuration. Consequently, the capacity of patients with anorexia nervosa to detoxify electrophilic metabolites and reactive oxygen species via glutathione may be impaired.

Acetaminophen↗
PubMed2003

Productive infection of cerebellar granule cell neurons by JC virus in an HIV+ individual.

BACKGROUND: In the setting of severe immunosuppression, the polyomavirus JC (JCV) can cause a lytic infection of oligodendrocytes. This demyelinating disease of the CNS white matter (WM) is called progressive multifocal leukoencephalopathy (PML). JCV has a very narrow host-cell range and productive infection of neurons has never been demonstrated. Patient, methods, and results: An HIV-1-infected patient presented with signs of pyramidal tract and cerebellar dysfunction. Brain MRI revealed T2 hyperintensities in the WM of both frontal lobes and cerebellar atrophy. His disease progressed despite therapy and he died 6 months later. In addition to classic PML findings in the frontal lobe WM, autopsy revealed scattered foci of tissue destruction in the internal granule cell layer (IGCL) of the cerebellum. In these foci, enlarged granule cell neurons identified by the neuronal markers MAP-2 and NeuN reacted with antibodies specific for the polyomavirus VP1 capsid protein. Electron microscopy showed 40 nm viral particles, consistent with polyomaviruses, in these granule cell neurons. In addition, JCV DNA was detected by PCR after laser capture microdissection of cells from the areas of focal cell loss. Finally, in situ hybridization studies demonstrated that many granule cell neurons were infected with JCV but did not contain viral proteins. Sequence analysis of the JCV regulatory region from cerebellar virions showed a tandem repeat pattern also found in PML lesions of the frontal lobe WM. CONCLUSION: JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation.

BACKGROUND: Reliable recording of motor evoked potentials (MEPs) of the masseter muscle by transcranial magnetic stimulation (TMS) has proved more difficult than from facial or intrinsic hand muscles. Up to now it was unclear whether this difficulty was due to methodological and/or anatomical reasons. METHODS: The mechanism of pyramidal cell activation in masseter MEPs was investigated by using magnetic and electric transcranial stimulation. Analysing the effect of magnetic coil positioning and orientation over the scalp, and scrutinizing the masseter recording technique to avoid compound motor action potential (CMAP) contamination from facial muscles, an optimized method of masseter MEPs was developed. RESULTS: In particular, an antero-lateral inducing current orientation in the stimulating coil, approximately paralleling the central sulcus, proved clearly more effective for the masseter muscles than the postero-lateral orientation (P=0.005) found optimal for intrinsic hand muscles. The thus evoked masseter MEPs by transcranial magnetic stimulation (TMS) were found to be identical in shape, amplitude and latency as those evoked by transcranial electric stimulation (TES), evidencing a direct rather than trans-synaptic activation of the pyramidal cells. CONCLUSIONS: We conclude that in TMS evoked MEPs of masseter muscles, the direct stimulation of the pyramidal tract is more easily achieved than the trans-synaptic activation, which is in contrast to the intrinsic hand muscles. We hypothesize that the presynaptic projections to pyramidal cells of the masticatory muscles are less abundant than in hand muscles, and are therefore less accessible to trans-synaptic stimulation.

Action Potentials↗
PubMed2000

[Children of mentally ill parents. Research perspectives exemplified by children of depressed parents].

Children of psychiatrically ill parents represent a risk group that has received growing attention during the last years. The risk for this group to develop a psychiatric illness is markedly increased due to genetic and psychosocial factors. The development of effective preventive concepts requires a thorough knowledge of the psychosocial factors. In this paper, deficits and problems of research in psychosocial transmission mechanism are discussed taking the example of children of depressive parents. Conclusions from this exemplary considerations may serve as guidelines for future research. The authors suggest that the focus be rather placed on coping strategies and developmental psychopathology. Further, research criteria are formulated that refer to theoretical models as well as to study design.

Adult↗
PubMed1991

The porcine tumor necrosis factor-encoding genes: sequence and comparative analysis.

We have cloned and sequenced a 10.22-kb fragment of the genomic locus of the porcine tumor necrosis factor-encoding genes, TNF-alpha and TNF-beta. A liver genomic DNA library, partially digested with Sau3AI, was cloned into the phage lambda EMBL4 and screened with a porcine TNF-alpha cDNA probe. Analysis showed that both the TNF-alpha and TNF-beta genes were present on the cloned fragment. In addition, the cloned fragment contained about 2 kb of repetitive sequences 5' to the TNF-beta gene. The TNF genes are arranged in a tandem repeat, as is the case for the human, mouse and rabbit TNF genes. The comparison of both genes with their human homologues displayed a considerable degree of conservation (80%), suggesting an equal evolution rate.

Animals↗
PubMed1984

Human blood platelet secretion: optical multichannel analyzer measurements using acriflavine as a release indicator.

Blood platelets preloaded with the fluorescent amine acriflavine release the trapped fluorophore after stimulation with thrombin or the divalent cation ionophore A23187. Release was detected by an increase in acriflavine fluorescence, which is otherwise strongly quenched in the platelet, by using an optical multichannel analyzer to monitor the spectral and temporal reaction parameters. The secretion of [14C]serotonin and acriflavine is well correlated, suggesting that acriflavine, like serotonin and the closely related fluorescent drugs mepacrine and acridine orange, is accumulated in and released from platelet dense bodies. Acriflavine secretion at 37 degrees C in the absence of external calcium is characterized by a short delay, followed by a rapid biphasic increase in fluorescence that implies at least a three-stage secretory process. For saturating levels of thrombin the delay was 1.5 s and release was 90% complete within 6-7 s. The delay could not be shortened by prestimulation under conditions that induce shape changes but not release, i.e., with ADP, arachidonic acid, or low levels of thrombin or A23187. Acriflavine secretion induced by A23187 was similar but less effective; the reaction was slower, the yield was smaller, and, in contrast to thrombin, the longer lag period could be significantly shortened by prestimulation.

Acriflavine↗
PubMed1981

A permeability change of myelin membrane vesicles towards cations is induced by MgATP but not by phosphorylation of myelin basic proteins.

The existence of an endogenous protein kinase activity and protein phosphatase activity in myelin membrane from mammalian brain has now been well established. We found that under all conditions tested the myelin basic protein is almost the only substrate of the endogenous protein kinase in myelin of bovine brain. The protein kinase activity is stimulated by Ca2+ in the micromolar range. Optimal activity is reached at a free Ca2+ concentration of about 2 microM. Myelin membrane vesicles were prepared and then shown to be sealed by a light-scattering technique. After preloading with 45Ca2+, 86Rb+, or 22Na+, the self-diffusion (passive outflux) of these ions from myelin membrane vesicles was measured. Ionophores induced a rapid, concentration-dependent outflux of 80--90% of the cations, indicating that only a small fraction of the trapped ions was membrane bound. There was no difference in the diffusion rates of the three cations whether phosphorylated (about 1 mol phosphate per myelin basic protein) or non-phosphorylated vesicles were tested. In contrast, a small but significant decrease in permeability for Rb+ and Na+ was measured, when the vesicles were pretreated with ATP and Mg2+.

Adenosine Triphosphate↗