[A woman with a tingling sensation in the hand].

A 57-year-old woman presented herself in the plastic surgery department's outpatient clinic at our hospital. She had been experiencing a tingling sensation of the first three digits of the left hand. Our first differential diagnosis was a classic carpal tunnel syndrome.

Analysis of Cre-mediated genetic deletion of in cardiomyocytes of young mice.

Administration of active growth differentiation factor 11 (GDF11) to aged mice can reduce cardiac hypertrophy, and low serum levels of GDF11 measured together with the related protein, myostatin (also known as GDF8), predict future morbidity and mortality in coronary heart patients. Using mice with a loxP-flanked ("floxed") allele of and -driven expression of Cre recombinase to delete in cardiomyocytes, we tested the hypothesis that cardiac-specific deficiency might lead to cardiac hypertrophy in young adulthood. We observed that targeted deletion of in cardiomyocytes does not cause cardiac hypertrophy but rather leads to left ventricular dilation when compared with control mice carrying only the or -floxed alleles, suggesting a possible etiology for dilated cardiomyopathy.

Targeting repulsive guidance molecule A to promote regeneration and neuroprotection in multiple sclerosis.

Repulsive guidance molecule A (RGMa) is a potent inhibitor of neuronal regeneration and a regulator of cell death, and it plays a role in multiple sclerosis (MS). In autopsy material from progressive MS patients, RGMa was found in active and chronic lesions, as well as in normal-appearing gray and white matter, and was expressed by cellular meningeal infiltrates. Levels of soluble RGMa in the cerebrospinal fluid were decreased in progressive MS patients successfully treated with intrathecal corticosteroid triamcinolone acetonide (TCA), showing functional improvements.

Establishment of a secondary screening assay for P/Q-type calcium channel blockers.

Development of calcium channel blockers is attractive, but has in the past been hampered by lack of high throughput electrophysiological technology. This limitation has been overcome by the implementation of automated patch clamp systems that allow identification of state-dependent compounds, which preferentially target pathologically overactive channels. We recently presented a fluorescence-based high-throughput screen for P/Q-type calcium channels followed by automated electrophysiology.

Development of disease-modifying treatment of schizophrenia.

Development of disease-modifying therapies requires an innovative approach to drug development where novel drugs are designed to target mechanisms of interest rather than to produce preclinical effects similar to those of currently used antipsychotics. Application of such novel strategy will undoubtedly require a very deep understanding of the disease biology that is just starting to emerge. Alternatively, one may let environmental experiences of the diseased individual guide the repair process and use drugs only to facilitate the effects of experience.