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Biomedical subjects

M Miñano

Publications and source records attributed to M Miñano.

3 recordsLinked to original sources

Relation between exploratory activity and immune function in aged mice: a preliminary study.

Previous studies show that fast exploration of a T-shaped maze by mature mice may predict an above average longevity. Since the nervous and the immune systems work in a coordinated fashion, and it seems that these two homeostatic systems both influence organismic aging and suffer a senescent decline, we have performed a comparative study of the above behavioral parameter and different functions of three representative immune cells: lymphocytes, macrophages and natural killer (NK) cells obtained from old (76 +/- 1 weeks of age) female OF1-Swiss mice. At 70 weeks of age the mice were divided into a 'fast' and a 'slow' group, containing 100 and 0%, respectively, of animals able to explore the 50 cm-long first arm of the maze in 20 s or less. At 76 +/- 1 weeks of age the animals were sacrificed, the peritoneal cell suspensions were obtained and the immune organs (axillary nodes, spleen and thymus) were isolated. The following leukocyte functions were studied in peritoneal macrophages: adherence to substrate, mobility (spontaneous and chemotaxis), ingestion of particles and superoxide anion production whereas mobility, lymphoproliferative response to the mitogen Con A and NK activity were studied in the immune-organ leukocyte suspensions. The results show that the aged fast mice have better immune functions than the aged slow mice.

Aging

Effects of endotoxic shock in several functions of murine peritoneal macrophages.

Gram negative sepsis and septic shock continue to be a major medical problem, with a complex physiopathology and it is associated with high mortality. Although secretion of cytokines such as tumor necrosis factor-alpha by macrophages is the principal host mediator of septic shock, other characteristic functions of macrophages implicated in their phagocytic capacity have not been studied in the process of endotoxic shock. In the present study we have used an intraperitoneal injection of E. coli lipopolysaccharide (LPS) (100 mg/kg) in order to obtain an endotoxic shock model in adult female BALB/c mice. Peritoneal cell suspensions were obtained at several times (2, 4, 12 or 24 h) after injection and the following functions were studied on the peritoneal macrophages: adherence to substrate, mobility (spontaneous and directed or chemotaxis), ingestion of particles and superoxide anion production. The results showed a stimulation of adherence, ingestion and superoxide production as well as a decrease of chemotaxis in the animals injected with LPS. These effects changed with time after LPS injection. Thus, the increase of adherence and the decrease of mobility were higher during the first hours, whereas the increase in ingestion and superoxide production turned larger with time.

Animals

Retinoic acid posttranscriptionally up-regulates proteolipid protein gene expression in C6 glioma cells.

The proteolipid protein (PLP) gene codes for the major central nervous system myelin protein. We have studied the effects of different agents on the expression of the PLP gene in C6 glioma cells. Retinoic acid (RA), but not dexamethasone, estradiol, insulin, growth hormone, or vitamin D3, had a drastic effect, increasing 10-20-fold the level of PLP mRNA. Concomitantly, RA also induced the appearance of the corresponding immunoreactive protein. The increase in PLP RNA level showed a slow kinetics and was blocked by cycloheximide, suggesting a posttranscriptional regulation by RA. Nuclear run-on assays confirmed that the rate of PLP gene transcription was unchanged by RA. In contrast, we found that retinoic acid augmented PLP mRNA stability, causing a substantial increase in its half-life. RA action was independent of cell density, serum, or PDGF but was partially inhibited by bFGF. On the other hand, thyroid hormone caused a moderate increase in PLP mRNA levels in C6 cells but only when the low numbers of thyroid receptors in these cells were increased by retrovirally mediated expression of an exogenous c-erbA/TR alpha-1 gene. Our results indicate that RA specifically up-regulates PLP expression in glioma C6 cells at a posttranscriptional level by increasing PLP RNA half-life.

Animals