Background/aims-Hepatocellular carcinoma (HCC) is a common malignant tumour worldwide, and its diVerential diagnosis from benign lesions of the liver is often diYcult yet of great clinical importance. In the present study, we analysed whether glypican-3 is useful in diVerentiating between benign and malignant liver diseases and whether it influences the growth behaviour of HCC. Conclusions-These findings suggest that glypican-3, in many cases, has the potential to diVerentiate between benign and malignant liver diseases. (Gut 2001;48:558-564)
Methods-Northern
The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons. Neural transcript expression of only one gene, encoding the Npas4 transcription factor, was >twofold altered (downregulated) in MET mice; strikingly, similar Npas4 downregulation occurred in the prefrontal cortex of human patients with schizophrenia. Finally, therapeutic actions of typical (haloperidol) and atypical (clozapine) antipsychotics in MET mice mimicked effects in human schizophrenia patients. Our data support the validity of MET mice as a model for schizophrenia, and uncover methionine metabolism as a potential preventive and/or therapeutic target.
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