Calcyon stimulates neuregulin 1 maturation and signaling.

Neuregulin1 (NRG1) is a single transmembrane protein that plays a critical role in neural development and synaptic plasticity. Both NRG1 and its receptor, ErbB4, are well-established risk genes of schizophrenia. The NRG1 ecto-domain (ED) binds and activates ErbB4 following proteolytic cleavage of pro-NRG1 precursor protein. Although several studies have addressed the function of NRG1 in brain, very little is known about the cleavage and shedding mechanism. Here we show that the neuronal vesicular protein calcyon is a potent activator and key determinant of NRG1 ED cleavage and shedding. Calcyon stimulates clathrin-mediated endocytosis and endosomal targeting; and its levels are elevated in postmortem brains of schizophrenics. Overexpression of calcyon stimulates NRG1 cleavage and signaling in vivo, and as a result, GABA transmission is enhanced in calcyon overexpressing mice. Conversely, NRG1 cleavage, ErbB4 activity and GABA transmission are decreased in calcyon null mice. Moreover, stimulation of NRG1 cleavage by calcyon was recapitulated in HEK 293 cells suggesting the mechanism involved is cell-autonomous. Finally, studies with site-specific mutants in calcyon and inhibitors for the major sheddases indicate that the stimulatory effects of calcyon on NRG1 cleavage and shedding depend on clathrin-mediated endocytosis, ß-secretase 1, and interaction with clathrin adaptor proteins. Together these results identify a novel mechanism for NRG1 cleavage and shedding.

The assessment of the cardiac compensatory function of elderly people with coronary artery disease by quantitive dobutamine stress echocardiography.

OBJECTIVE: The aim of the study is to investigate the cardiac compensatory function change in senior people with Coronary Artery Disease (CAD) by Quantitive Dobutamine Stress Echocardiography (DSE) and Tissue Doppler Imaging (TDI). PATIENTS AND METHODS: All of the 98 senior people (age >60) who were suspected to have CAD received the examination of DSE and TDI. The mean systolic peak velocity (Sa), early diastolic peak velocity (Ea) and late diastolic peak velocity (Aa) of mitral annulus were measured in a different dose of dobutamine stress. Besides, the coronary angiography (CAG) was done within 2 weeks for the 98 senior people. RESULTS: In the basic status, the mean Sa, Ea and Aa were not significantly different between the patients from the normal group and CAD group. However, under a 20 µg/kg·min dose of dobutamine stress, significant differences of mean Sa and Ea between two groups were observed. For the mean Aa, a significant difference could be observed with the dose of 40 µg/kg·min. CONCLUSIONS: Both the cardiac systolic and diastolic compensatory function were lower in the CAD group than the normal group, which is detectable in the 20 µg/kg·min dose of dobutamine stress status. In other words, Quantitive Dobutamine Stress Echocardiography is a safe, efficient, non-invasive diagnostic method. It can reflect the compensatory cardiac function of the patients with CAD.

[Immune status of oral lichen planus and squamous cell cancer patients-T subgroup cells evaluation in PBL]

The levels of T-subgroup cells for 30 oral lichen planus(LP) and 25 cancers are reported.15 health are constracted.The results are as follows:Health OKT value T(3) 62.8+/-1.81,T(4) 44.4+/-7.34,T(8) 25.5+/-0.71,T(4)/T(8) 1.79+/-0.13;OLP OKT value:T(3) 53.2+/-1.92,T(4) 40.2+/-1.9, T(8)38.61+/-2.2, T(4)/T(8) 1.10+/-0.07,Cancer value 52.9+/-1.9,40.2+/-2.3,36.4+/-2.05,1.17+/-0.09. Both group of patients were compared with health.The level of OKT(3) OKT(4)/OKT(8) was decreased significantly(0.001),but OKT(8) qA increased significantly(0.001).This shows that T cell immune function is decreased in the oral LP and cancer patients.