Key role of ATF3 in p53-dependent DR5 induction upon DNA damage of human colon cancer cells.

Stress response gene ATF3 is one of the p53 target genes and has a tumor suppressor role in cancer. However, the biological role of p53-ATF3 pathway is not well understood. Death receptor 5 (DR5) is a death domain-containing transmembrane receptor that triggers cell death upon binding to its ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and a combination of TRAIL and agents that increase the expression of DR5 is expected as a novel anticancer therapy. In this report, we demonstrate that ATF3 is required for efficient DR5 induction upon DNA damage by camptothecin (CPT) in colorectal cancer cells. In the absence of ATF3, induction of DR5 messenger RNA and protein is remarkably abrogated, and this is associated with reduced cell death by TRAIL and CPT. By contrast, exogenous expression of ATF3 causes more rapid and elevated expression of DR5, resulting in enhanced sensitivity to apoptotic cell death by TRAIL/CPT. Reporter assay and DNA affinity precipitation assay demonstrate that at least three ATF/CRE motifs at the proximal promoter of the human DR5 gene are involved in the activation of DNA damage-induced DR5 gene transcription. Furthermore, ATF3 is shown to interact with p53 to form a complex on the DR5 gene by Re-chromatin immunoprecipitation assay. Taken together, our results provide a novel insight into the role of ATF3 as an essential co-transcription factor for p53 upon DNA damage, and this may represent a useful biomarker for TRAIL-based anticancer therapy.

[AML(M7) associated with t(16;21)(p11;q22) showing relapse after unrelated bone marrow transplantation and disappearance of TLS/FUS-ERG mRNA].

A 3-year-old boy with poorly prognostic acute megakaryoblastic leukemia (AML M7) showing t(16;21)(p11;q22) karyotype underwent unrelated bone marrow transplantation (U-BMT) during his first hematological remission. The conditioning regimen consisted of BU, VP-16 and L-PAM. Engraftment was smooth, but the patient developed grade I acute GVHD. During hematological remission before U-BMT, the TLS/FUS-ERG chimeric transcript of t(16;21)(p11;q22) was consistently detectable as minimal residual disease (MRD) by RT-PCR. However, after U-BMT it soon became undetectable. There was no detectable MRD until 7 months after U-BMT, but bone marrow relapse occurred 10 months after U-BMT. We consider that U-BMT is a promising treatment for t(16;21)(p11;q22) AML. However, an intensified conditioning regimen or modification of GVHD prophylaxis is needed.

[Excitatory effect of noradrenaline on rat airway parasympathetic ganglion neurons].

The effects of noradrenaline (NAd) on neurons acutely isolated from airway parasympathetic ganglia of rats were investigated by use of the nystatin perforaded-patch recording mode. Under current-clamp conditions, an application of 10(-6) M NAd onto the ganglion neurons evoked a depolarization which was accompanied by regenerating repetitive action potentials. NAd concentration-dependently induced inward current with decreasing membrane conductance when a ganglion neuron was held at a holding potential of -40 mV. The half-maximum effective concentration (EC50) of NAd was 1.7 x 10(-7) M, and the response was mimicked by an alpha 1-adrenoceptor agonist cirazoline and was inhibited by WB-4101, an alpha 1A-adrenoceptor antagonist. Oxymetazoline, a partial agonist for an alpha 1A-adrenoceptor, also evoked the inward current with an EC50 of 3.5 x 10(-8) M. The maximum current induced by oxymetazoline (10(-6) M) was 44% of that induced by NAd. NAd also inhibited the amplitude of M-current deactivation induced by hyperpolarizing step from a VH of -25 mV to -50 mV with an EC50 of 2.0 x 10(-4) M. These results suggest that NAd directly depolarizes the airway parasympathetic ganglion neurons of rats associated with an inhibition of M-current through the alpha 1A-adrenoceptors.

Suicide and suicide attempts in general hospital psychiatry: clinical and statistical study.

Thirty-six psychiatric patients with completed suicide, 162 with attempted suicide and 154 patients referred for suicidal behavior, four of whom died, were investigated and classified according to the ICD-10. Thirty-six patients with completed suicide among 9085 new psychiatric patients (1969-92) gave a suicide rate of 82.6/100 000 per year. Schizoaffective and depressive disorder in psychiatric patients with completed suicide and schizophrenia, depressive disorder and adjustment disorders in patients with attempted suicide were significantly more frequent than in 312 controls. Intrafamilial conflicts, divorce or loss of love and death or severe disease of family member were the most common precipitants. Loneliness from living alone in males, losing a spouse and intrafamilial conflicts within a large family of three generations in females were supposed to be risk factors. A high referral rate of 48% in attempted suicide indicated the important role of consultation-liaison psychiatry in emergency medicine.

Psychogeriatric patients in a general hospital: role of geropsychiatric consultation.

A total of 505 elderly patients aged 65 and over, seen at the Department of Psychiatry of Tosei General Hospital, were investigated retrospectively and classified according to the DSM-III-R criteria. The increase in the number of psychogeriatric patients over the last two decades was statistically significant. Organic mental disorders were most frequent (51%), followed by mood disorders (22%), sleep disorders (7%), somatoform disorders (6%), anxiety disorders (5%) and others. A high referral rate (42%) and a high incidence of various concurrent physical disorders (52%) were observed, and the role of geropsychiatric consultation in a general hospital was evaluated and discussed.