Hereditary spherocytosis (HS), a common human inherited haemolytic anaemia, is associated with partial deficiency of different erythrocyte membrane proteins. In a subset of dominant HS, a partial membrane expression deficiency of band 3, the erythrocyte anion exchanger (AE1), have previously been characterized, and several mutations in the band 3 gene have been found: amino acid substitutions at conserved positions in the membrane domain, nonsense and frameshift mutations. In HS patients bearing missense mutations, the mutated transcript was present, whereas only the normal transcript was found in HS patients with frameshift mutations. In the former group, the membrane expression deficiency of band 3 was significantly more important than that observed in the latter group of HS patients with frameshift mutations, suggesting that missense mutations may have a dominant negative effect. In the present study, transient and stable transfections of K562 and COS-7 cells were used to demonstrate, by immunoblots of cell lysates and immunofluorescence studies, that the band 3 membrane domain bearing the R490C mutation (band 3Bicetrel) is not targeted to the plasma membrane and is retained in the endoplasmic reticulum. Transient cotransfections of K562 cells with plasmid coding for the normal membrane domain of band 3, together with increasing amounts of plasmid coding for the mutated R490C membrane domain, demonstrated that the band 3 mutant polypeptide exerts a dominant negative effect on the plasma membrane targeting of the normal band 3.

Animals↗

PubMedDate not supplied

A randomized controlled trial of cognitive therapy versus intensive behavior therapy in obsessive compulsive disorder.

BACKGROUND: The study was designed to compare cognitive therapy (CT) with intensive behavior therapy (BT) in obsessive-compulsive disorder (OCD) and to study their change process. METHODS: Sixty-five outpatients with DSM-4 OCD were randomized into 2 groups for 16 weeks of individual treatment in 3 centers. Group 1 received 20 sessions of CT. Group 2 received a BT program of 20 h in two phases: 4 weeks of intensive treatment (16 h), and 12 weeks of maintenance sessions (4 h). No medication was prescribed. RESULTS: Sixty-two patients were evaluated at week 4, 60 at week 16 (post-test), 53 at week 26 and 48 at week 52 (follow-up). The response rate was similar in the 2 groups. The Beck Depression Inventory (BDI) was significantly more improved by CT (p = 0.001) at week 16. The baseline BDI and Obsessive Thoughts Checklist scores predicted a therapeutic response in CT, while the baseline BDI score predicted a response in BT. At week 16, only the changes in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a scale measuring the interpretation of intrusive thoughts correlated in CT, while the changes in Y-BOCS, BDI, and interpretation of intrusive thoughts correlated in BT. Improvement was retained at follow-up without a between-group difference. The intent-to-treat analysis (last observation carried forward) found no between-group differences on obsessions, rituals and depression. CONCLUSIONS: CT and BT were equally effective on OCD, but at post-test CT had specific effects on depression which were stronger than those of BT. Pathways to improvement may be different in CT and BT. The outcomes are discussed in the light of an effect size analysis.

Adult↗

PubMedDate not supplied

Anomalous origin of all coronary arteries from the pulmonary trunk.

The origin of both coronary arteries from the pulmonary artery is a rare cardiac malformation. We report a baby who presented with an echocardiographically diagnosed perimembranous ventricular septal defect and normal left ventricular (LV) function. Later on the boy developed failure to thrive and increasing tachypnea. At the age of 5 weeks the ECG showed that LV strain and echocardiographic LV function had worsened (FS 18%). Echocardiography and heart catheterization showed that all coronary arteries originated from the pulmonary trunk. Intraoperative inspection revealed a single ostium for the right and left coronary artery in the nonfacing sinus of the pulmonary trunk. A tube was constructed connecting the coronary artery to the ascending aorta. Coronary perfusion was sufficient and the sinus rhythm was restored. However, in the early postoperative period there was a sudden deterioration of cardiac output followed by cardiac arrest. Reanimation was not successful.

Abnormalities, Multiple↗