X-Munich : cas pràctic

Berneda S.A. és una “pime” familiar catalana no cotitzada que es va fundar l’any 1939. També coneguda per ser l’empresa posseïdora de la marca X-Munich, destaca per la seva capacitat d’autofinançament.Al llarg de la seva història Berneda S.A. ha sabut guanyar-se el mercat en diverses etapes i, tot i haver viscut períodes de menys facturació, des de l’any 2007 ha gaudit d’un boom de les seves vendes al mercat espanyol. Part d’aquest creixement del volum de vendes i ingressos està relacionat també amb la seva capacitat exportadors: actualment les seves sabatilles esportives es comercialitzen, entre d’altres, a Itàlia, Holanda, Japó, Gran Bretanya i Portugal.Berneda S.A. ha aprofitat el seu avantatge competitiu, la diferenciació, per a oferir al mercat un producte diferent i posicionar-se com a una marca de referencia en el sector.

Retinal ischemia-induced apoptosis is associated with alteration in Bax and Bcl-x(L) expression rather than modifications in Bak and Bcl-2.

PURPOSE: Apoptosis is known to play a key role in cell death after retinal ischemia. However, little is known about the kinetics of the signaling pathways involved and their contribution to this process. The aim of this study was to determine whether changes in the expression of molecules in the mitochondrial apoptotic pathway might explain the progression of retinal damage following ischemia/reperfusion. METHODS: Retinal ischemia was induced by elevating intraocular pressure in the vitreous cavity to 150 mmHg for a period of 60 min. At time 0, 3 h (early phase), and 24 h (late phase) after reperfusion, the retinas were harvested and modifications in the expression of Bax, Bak, Bcl-2, and Bcl-x(L) as well as caspase-3 and -7, were examined by qPCR and, in some cases, by western blot. RESULTS: qPCR analysis performed at the early phase after ischemia revealed a time dependent decrease in Bax, Bak, and Bcl-x(L) and no alteration in Bcl-2 mRNA expression in response to retinal ischemia. At the protein level, proapoptotic Bax and Bak were not modulated while Bcl-2 and Bcl-x(L) were significantly upregulated. At this stage, the Bax per Bcl-2 and Bax:Bcl-x(L) ratios were not modified. At the late phase of recovery, Bax and Bcl-x(L) mRNAs were downregulated while Bak was increased. Increased Bax:Bcl-2 and Bax:Bcl-x(L) ratios at both the mRNA and protein levels were observed 24 h after the ischemic insult. Analysis of caspases associated with mitochondria-mediated apoptosis revealed a specific increase in the expression of caspase-3 in the ischemic retinas 24 h after reperfusion, and a decrease in the expression of caspase-7. CONCLUSIONS: This study revealed that Bcl-2-related family members were differently regulated in the early and late phases after an ischemic insult. We showed that the Bax:Bcl-2 and Bax:Bcl-x(L) balances were not affected in the initial phases, but the Bax:Bcl-x(L) ratio shifted toward apoptosis during the late phase of recovery. This shift was reinforced by caspase-3 upregulation.

A novel interferon-gamma regulated human melanoma-associated antigen, gp33-38, defined by monoclonal antibody Me14-D12. II. Molecular cloning of a genomic probe.

The human Me14-D12 antigen is a cell surface glycoprotein regulated by interferon-gamma (IFN-gamma) on tumor cell lines of neuroectodermal origin. It consists of two non-convalently linked subunits with apparent mol. wt sizes of 33,000 and 38,000. Here we describe the molecular cloning of a genomic probe for the Me14-D12 gene using the gene transfer approach. Mouse Ltk- cells were stably cotransfected with human genomic DNA and the Herpes Simplex virus thymidine kinase (TK) gene. Primary and secondary transfectants expressing the Me14-D12 antigen were isolated after selection in HAT medium by repeated sorting on a fluorescence activated cell sorter (FACS). A recombinant phage harboring a 14.3 kb insert of human DNA was isolated from a genomic library made from a positive secondary transfectant cell line. A specific probe derived from the phage DNA insert allowed the identification of two mRNAs of 3.5 kb and 2.2 kb in primary and secondary L cell transfectants, as well as in human melanoma cell lines expressing the Me14-D12 antigen. The regulation of Me14-D12 antigen by INF-gamma was retained in the L cell transfectants and could be detected both at the level of protein and mRNA expression.

Long-term, multilineage hematopoiesis occurs in the combined absence of beta-catenin and gamma-catenin

The canonical Wnt signaling pathway plays key roles in stem-cell maintenance, progenitor cell expansion, and lineage decisions. Transcriptional responses induced by Wnt depend on the association of either beta-catenin or gamma-catenin with lymphoid enhancer factor/T cell factor transcription factors. Here we show that hematopoiesis, including thymopoiesis, is normal in the combined absence of beta- and gamma-catenin. Double-deficient hematopoietic stem cells maintain long-term repopulation capacity and multilineage differentiation potential. Unexpectedly, 2 independent ex vivo reporter gene assays show that Wnt signal transmission is maintained in double-deficient hematopoietic stem cells, thymocytes, or peripheral T cells. In contrast, Wnt signaling is strongly reduced in thymocytes lacking TCF-1 or in nonhematopoietic cells devoid of beta-catenin. These data provide the first evidence that hematopoietic cells can transduce canonical Wnt signals in the combined absence of beta- and gamma-catenin

Gamma Knife radiosurgery in benign skull base tumors after planned subtotal resection: preliminary results in combined approaches

Aim: The management of large lesions of the skull base, such as vestibular schwanommas (VS), meningiomas (MEN) or pituitary adenomas (PA), is challenging, with microsurgery remaining the main treatment option. Planned subtotal resection is now being increasingly considered to reduce the risk of neurological deficits following complete resection. The residual part of the tumor can then be treated with Gamma Knife Radiosurgery (GKR) to achieve long-term growth control. Methods: This case series documents early results with planned subtotal resection followed by GKR in Lausanne University Hospital, between July 2010 and March 2012. There were 24 patients who underwent surgery, with 22 having already undergone GKR and 2 waiting for GKR. We analyzed clinical symptoms for all patients, as well as audiograms, ophthalmological and endocrinological tests, when indicated. Results: Nine patients had VS surgery (mean diameter 35 mm; range 30-44.5) through a retrosigmoid approach. There were no post-operative facial nerve deficits. Of the 3 patients whom had useful hearing pre-operatively, this improved in 2 and remained stable in 1. Four patients with clinoid MEN (mean diameter 26.5 mm; range 17-42) underwent subtotal resection of the tumor, and the component in the cavernous sinus was later treated with GKR. The visual status remained stable in 3 patients and one had complete visual recovery. 4 patients underwent subtotal resection of petro-clival MEN (mean diameter 36 mm; range 32-42): 3 had House-Brackmann (HB) grade 2 facial function that recovered completely; one continues to have HB grade 4 facial deficit following surgery. Of the 7 patients with PA (mean diameter 34.5 mm; range 20-54.5), 2 had acromegaly, the others were non functional PA. Six patients underwent trans-sphenoidal surgery, while one patient had a transcavernous sinus resection of the tumor (with prior staged trans-sphenoidal surgery). Visual status improved in 3 patients while the others remained stable. Two patients had transient diabetes insipidus following surgery. Up to now, no additional deficit or worsening has been reported after GKR. Conclusions: Our data suggest that planned subtotal resection has an excellent clinical outcome with respect to preservation of cranial nerves, and other neurological functions, and a good possibility of recovery of many of the pre-operative cranial nerve dysfunctions. The results in terms of tumor control following GKR need further long-term evaluation.

Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice.

This study demonstrates that endogenously produced interferon gamma (IFN-gamma) forms the basis of a tumor surveillance system that controls development of both chemically induced and spontaneously arising tumors in mice. Compared with wild-type mice, mice lacking sensitivity to either IFN-gamma (i.e., IFN-gamma receptor-deficient mice) or all IFN family members (i.e., Stat1-deficient mice) developed tumors more rapidly and with greater frequency when challenged with different doses of the chemical carcinogen methylcholanthrene. In addition, IFN-gamma-insensitive mice developed tumors more rapidly than wild-type mice when bred onto a background deficient in the p53 tumor-suppressor gene. IFN-gamma-insensitive p53(-/-) mice also developed a broader spectrum of tumors compared with mice lacking p53 alone. Using tumor cells derived from methylcholanthrene-treated IFN-gamma-insensitive mice, we found IFN-gamma's actions to be mediated at least partly through its direct effects on the tumor cell leading to enhanced tumor cell immunogenicity. The importance and generality of this system is evidenced by the finding that certain types of human tumors become selectively unresponsive to IFN-gamma. Thus, IFN-gamma forms the basis of an extrinsic tumor-suppressor mechanism in immunocompetent hosts.