Analysis of c-erb A RNA expression in the triiodothyronine-sensitive Ob 17 preadipocyte cell line.

The protooncogenes erb A alpha and beta encode, in the rat, three functional thyroid hormone receptors (erb A alpha 1, beta 1 and beta 2), and two isoforms (erb A alpha 2, alpha 3) that do not bind triiodothyronine (T3). We previously reported on a mouse preadipocyte cell line (Ob 17) which was found to be sensitive to thyroid hormones and retinoic acid. Using antibodies or cDNA probes, we reported that the c-erb A products are mainly of the alpha-type in these cells. We also showed that the thyroid hormone receptors/c-erb A products are down-regulated moderately by T3 and strongly by retinoic acid added to the culture medium. In this work, different c-erb A subtypes are identified in this mouse cell line. Using couples of oligonucleotides known to be specific of each rat c-erb A subtype, we could detect the presence of alpha 1, alpha 2 and beta 1-type transcripts. We also detected Rev transcripts of a Reverse erb A alpha gene present in the rat at the c-erb A alpha locus and that contains a region complementary to the c-erb A alpha 2-specific region. These transcripts were identified by PCR amplification from cell cDNAs and in Northern analyses using the corresponding PCR-designed c-erb A probes. All the detected transcripts were found to be down-regulated by retinoic acid.

[Nifedipine in the treatment of chronic cor pulmonale]. / Apport de la nifédipine dans le traitement du coeur pulmonaire chronique.

The effects of a single dose of nifedipine (20 mg sublingual) on the haemodynamics and parameters of tissue oxygenation were assessed by right heart catheterisation and oximetry of mixed arterial and venous blood in 24 patients with pulmonary hypertension secondary to severe chronic obstructive airways disease. The haemodynamic effects of 15 days' oral therapy (30 mg/day) were studied in 10 other patients. Significant improvement in right ventricular pump function (25 p. 100 increase in cardiac index. average reduction of 3 mmHg of right ventricular end diastolic pressure), and lowering of pulmonary hypertension (mean pulmonary artery pressures reduced by an average of 10 p. 100 and total pulmonary resistance by 25 p. 100) were observed after the single dose of nifedipine. This improvement was maintained after oral therapy for 15 days. The significant improvement of tissue oxygenation was reflected by an increase in oxygen transport (+ 24 p. 100), in the coefficient of delivered oxygen (+ 19 p. 100), in the oxygen partial pressure (+ 4 p. 100) and saturation (+ 3 p. 100) in the mixed venous blood. Arterial lactate concentrations fell by about 28 p. 100. In addition, a moderate fall in ppO2 and arterial saturation was observed due to a weak shunt effect which was more than compensated by the increase in cardiac output, and especially by the increase in the coefficient of relieved oxygen. These results show that nifedipine may be a valuable addition in the treatment of cor pulmonale secondary to chronic obstructive airways disease by improving right ventricular haemodynamics and pulmonary circulation and by increasing the quantity of oxygen delivered.

Two-week nifedipine treatment for pulmonary hypertension complicating chronic obstructive lung disease.

The effects of nifedipine on hemodynamics and blood gases were studied in 10 patients with pulmonary hypertension secondary to chronic obstructive lung disease. Two different sets of test data were recorded. The first set of readings was taken immediately before and during the initial hour after sublingual administration of 20 mg of nifedipine. The second set was taken after 2 weeks of therapy with 3 X 10 mg per day. After the acute sublingual dose, a significant decrease in pulmonary arterial pressure and pulmonary vascular resistance was recorded: 13% and 26% respectively. This decrease was accompanied by a 32% increase in cardiac output. Similar findings were recorded at the end of the 2-week therapy. Moreover, at this time, although blood gas tension had not been significantly altered, oxygen delivery was 35% higher. No adverse side effects were observed. This study suggests that nifedipine therapy can improve hemodynamics and tissue oxygenation in patients with pulmonary hypertension complicating chronic obstructive lung disease.