The transcription factor PAX4 acts as a survival gene in INS-1E insulinoma cells.

The paired/homeodomain transcription factor Pax4 is essential for islet beta-cell generation during pancreas development and their survival in adulthood. High Pax4 expression was reported in human insulinomas indicating that deregulation of the gene may be associated with tumorigenesis. We report that rat insulinoma INS-1E cells express 25-fold higher Pax4 mRNA levels than rat islets. In contrast to primary beta-cells, activin A but not betacellulin or glucose induced Pax4 mRNA levels indicating dissociation of Pax4 expression from insulinoma cell proliferation. Short hairpin RNA adenoviral constructs targeted to the paired domain or homeodomain (viPax4PD and viPax4HD) were generated. Pax4 mRNA levels were lowered by 73 and 50% in cells expressing either viPax4PD or viPax4HD. Transcript levels of the Pax4 target gene bcl-xl were reduced by 53 and 47%, whereas Pax6 and Pdx1 mRNA levels were unchanged. viPax4PD-infected cells displayed a twofold increase in spontaneous apoptosis and were more susceptible to cytokine-induced cell death. In contrast, proliferation was unaltered. RNA interference-mediated repression of insulin had no adverse effects on either Pax4 or Pdx1 expression as well as on cell replication or apoptosis. These results indicate that Pax4 is redundant for proliferation of insulinoma cells, whereas it is essential for survival through upregulation of the antiapoptotic gene bcl-xl.

[Drug addiction and personality disorder : reflection on treatment.]. / Toxicomanie et trouble de la personnalité : réflexion sur le traitement.

The experience of a treatment in cooccurring disorders of drug addiction and mental health has allowed to document the intervention with people presenting one or more personality disorders. This article describes the integrated program in which is inserted the trajectory of these people. The article highlights the complexity of their clinical portrait as well as the implications of the most current interventions in their treatment. It also underlines some critical moments of this clientele's path. Clinical vignettes are presented to better illustrate remarks. The authors' reflection leads to reconsidering conditions of the intervention. The avenue proposed is that of a differienciated, intermittent but continuous treatment. The possibility of a long term individual treatment for clients adopting this mode, is also considered. This range of possibilities would better respond to the specific chronicity of these two disorders.

Laser bronchoscopy.

Because the lung cancer epidemic shows no signs of abating, little doubt exists that the need for interventional bronchoscopists will persist for many years to come. The Nd:YAG laser and the rigid bronchoscope remain crucial weapons in the fight against lung cancer. With more than 4000 published interventions pertaining to it, this combination is ideal for treating central airways obstruction. The safety and efficacy of laser bronchoscopy has been well established, and the reported incidence of complications is impressively low. If complications were to arise, a skilled bronchoscopist can manage them easily by using the beneficial attributes of the rigid bronchoscope. Many complications can be avoided by implementing the established safety procedures and techniques. A solid understanding of laser physics and tissue interactions is a necessity to anyone performing laser surgery. The team approach, relying on communication among the bronchoscopist, anesthesiologist, laser technician, and nurses, leads to a safer and more successful procedure. It is important to remember, however, that this is typically a palliative procedure, and therefore the focus should be on alleviating symptoms and improving quality of life. Unfortunately, because not every patient is a candidate for laser bronchoscopy, there are specific characteristics of endobronchial lesions that make them more or less amenable to resection. Each year a promising new technology is being developed, such as argon plasma coagulation, cryotherapy, and endobronchial electrosurgery. Although it is unclear what role these technologies will have, prospective controlled studies must be done to help clarify this question. The future may lay in combining these various technologies along with Nd:YAG laser bronchoscopy to maximize the therapeutic, palliative, and possibly even curative effect. As the experience of the medical community with Nd:YAG laser bronchoscopy continues to grow and as more health-care professionals are made aware of its therapeutic capability, fewer patients with cancer will need to suffer and die from the complications of airway obstruction.

Interaction of beta-cyclodextrin with bile acids and their competition with vitamins A and D3 as determined by 1H-NMR spectrometry.

The interaction of beta-cyclodextrin (beta-CD) with four bile acids, cholic, taurocholic, chenodeoxycholic and lithocholic, was demonstrated by proton-NMR spectroscopy. Lithocholic and chenodeoxycholic acids exhibit a stronger affinity for beta-CD than cholic and taurocholic acids. The affinity of bile acids for beta-CD increases in relation to their hydrophobicity. The competition between these bile acids and the lipophilic vitamins A and D3 in the formation of beta-CD inclusion complexes was studied. These vitamins compete with cholic and taurocholic acids whereas they do not with lithocholic and chenodeoxycholic acids. In the latter case all of the beta-CD present was consumed by the bile acids with the vitamins remaining free in the medium. The affinity of vitamins A and D3 for beta-CD is lower than that of the bile acids. Therefore, when lithocholic or chenodeoxycholic acids are present, the formation of beta-CD inclusion complexes with the vitamins does not occur. The results of this study suggest that depletion of lipophilic vitamins will not occur upon ingestion of beta-CD, thus providing further support for the safety and suitability of beta-CD as an ingredient in foods and orally administered drugs.

Adoptive transfer of diabetes in BB rats induced by CD4 T lymphocytes.

Unseparated splenocytes (SPCs) or purified SPC subsets from diabetes-prone BB (BBdp) or diabetic BB (BBd) rats were activated in vitro with either phorbol myristate acetate (PMA) and ionomycin (I) or concanavalin A (ConA). Such activated SPCs were then injected intravenously into 30-day-old BBdp rats, and their capacity to induce adoptive transfer (AT) of diabetes was studied. The proliferative response in vitro of BBd unseparated SPCs or purified W3/13+ SPCs (i.e., T lymphocytes + large granular lymphocytes) to PMA + I far exceeded that of ConA, resulting in mean stimulation indices of 68 and 112 (PMA + I) and 1.9 and 30 (ConA). The incidence of AT was similar when equal numbers of unseparated SPCs from the same BBd donor were injected after activation by either PMA + I + interleukin 2 (PII) or ConA (57 vs. 50%, respectively); however, injection of PII-activated and macrophage-depleted W3/13+ SPCs from BBd animals resulted in a significantly higher incidence of AT (90%, P less than 0.05). As few as 0.5 x 10(6) PII-activated W3/13+ SPCs were sufficient to induce AT. Sixteen percent of recipients developed diabetes after injection of activated W3/13+ cells from 40-day-old BBdp donors. To determine which W3/13+ cells might mediate such transfer, purified and PII-preactivated CD4 T lymphocytes from BBd rats were injected, and they succeeded in AT in 44% of the recipients. Preactivated BBd B lymphocytes were unable to induce AT. Although a possible role for large granular lymphocytes cannot be excluded, the results demonstrate that in the BB rat, the beta-cell destruction can be induced by CD4 T lymphocytes.

Prolactin and the gut: a controversy.

Previous reports suggest that prolactin could be one of the factors controlling intestinal mucosal growth. Therefore plasma levels of prolactin have been measured at the time of jejunal biopsy performed for suspicion of celiac disease. One hundred eighty-seven biopsies from 166 children have been reviewed according to histology, age, diagnosis, and plasma prolactin. No difference in the plasma prolactin could be detected among a group of 117 normal biopsies (9.4 +/- 0.4 ng/ml, mean +/- SEM), 31 biopsies with partial atrophy of various degree (9.0 +/- 0.9 ng/ml), and 39 biopsies with flat mucosa (9.1 +/- 0.7 ng/ml), nor could we demonstrate an increase in prolactin according to age and diagnosis (celiac disease before and after treatment, cow's milk protein intolerance, isolated postenteritic syndrome, selective sugar intolerance, and functional gut problems). Prolactinlike material has been detected by immunoperoxidase in the jejunal mucosa. The intracellular granules are located in the infranuclear portion of isolated epithelial cells mainly in the crypts. This material could not be correlated with the corresponding prolactinemias, whatever the histological appearance of the mucosa. These results would suggest that plasma prolactin is not a marker of jejunal regeneration in children. The nature and function(s) of this prolactinlike material remain to be established.