Activation of the recombination activating gene 1 (RAG-1) transcript in bone marrow of senescent C57BL/6 mice by recombinant interleukin-7.

The level of the recombination activating gene 1 (RAG-1) mRNA in bone marrow cells decreases to a minimal level by the age of 10 months. Recominbant interleukin-7 (rIL-7) is a potent proliferative stimulus for B cell progenitors and upregulates RAG-1 expression in lymphocyte precursors. To investigate the stimulatory effect of rIL-7 on the expression of RAG-1 in old mice, we compared the level of RAG-1 message in short-term bone marrow cultures of cells from mice aged 1 month and 18 months. We found similar levels of RAG-1 mRNA in bone marrow cells of young mice before and after 24 hours of incubation. No RAG-1 mRNA was detected in bone marrow cell cultures prepared from old mice after 24 hours of incubation. However, when rIL-7 was added to the culture medium, RAG-1 mRNA was detected after 24 hours of incubation and its level was similar to that measured in cells from young mice. The expression of RAG-1 was dose-dependent, with 20 ng of rIL-7 per 10(6) old nucleated cells yielding the maximal response. Our results indicate that despite the low or no RAG-1 expression in bone marrow cultures of old mice, the potential to activate RAG-1 in B-cell precursors is still present, and immunoglobulin heavy chain (V(H)D(H)J(H)) rearrangement may be enhanced by rIL7.

Checkpoints in thymocytopoiesis in aging: expression of the recombination activating genes RAG-1 and RAG-2.

The study was designed to establish whether the ability to rearrange the T cell receptor (TCR) Vbeta genes is altered with age. We examined the expression of recombinase activating genes, RAG-1 and RAG-2, in the thymus of mice at different ages (2-24 months). A significant age-related decrease in RAG-1 and RAG-2 expression was observed in the thymocytes from the age of 12 months and over. To find out if this decrease is determined in the thymocyte progenitors or induced by the thymic microenvironment, we co-cultured lymphoid depleted fetal thymus (FT) explants with bone marrow cells, or immature thymocytes, from young and old mice. The developing thymocytes were examined at different time intervals during the first week of culture. Whereas cells derived from the immature thymocytes of the old donors failed to express RAG-1 and RAG-2, compared to the young, the bone marrow derived cells of both age groups did show this expression, and there was no difference in Vbeta rearrangement of the TCR. Our study indicates that T cell progenitors in the aging bone marrow retain the potential to give rise to T cells with TCR rearrangements, and the expression is determined by the thymic stroma.

Dibenzepin overdose causing pulmonary edema.

OBJECTIVE: To report a case of pulmonary edema due to dibenzepin overdose. CASE SUMMARY: A 39-year-old woman was hospitalized 24 hours after she ingested eight tablets of dibenzepin hydrochloride delayed-release 240 mg/tablet (approximately 35 mg/kg body weight). On admission the patient was confused, and physical examination revealed sinus tachycardia (HR 130 beats/min). Forty-five hours after ingestion of the dibenzepin she developed pulmonary edema and was treated with furosemide, morphine, and mechanical ventilation through an endotracheal tube for 48 hours. Repeated echocardiography revealed left ventricular dysfunction that resolved as the medical condition of the patient improved. Appropriate studies excluded pneumonia, pneumonitis, adult respiratory distress syndrome, myocardial infarction, and pulmonary emboli as contributing factors to this patient's condition. DISCUSSION: Tricyclic antidepressant overdose is known to cause cardiopulmonary complications, including pulmonary edema. To the best of our knowledge, this is the first reported case of pulmonary edema as a result of dibenzepin overdose. The most probable mechanism for this complication is depression of the left ventricular function. CONCLUSIONS: As with other tricyclic antidepressants, dibenzepin toxicity may cause pulmonary edema. Close patient monitoring is essential for at least 48-72 hours after the overdose.