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Joan Gil

Publications and source records attributed to Joan Gil.

At least 19 recordsLinked to original sources
PubMed2006

Glycogen synthase kinase-3beta binds to E2F1 and regulates its transcriptional activity.

GSK3beta and E2F1 play an important role in the control of proliferation and apoptosis. Previous work has demonstrated that GSK3beta indirectly regulates E2F activity through modulation of cyclin D1 levels. In this work we show that GSK3beta phosphorylates human E2F1 in vitro at serine 403 and threonine 433, both residues localized at its transactivation domain. This phosphorylation was not detected in vivo. However, co-immunoprecipitation experiments do reveal in vivo binding of these proteins. Moreover, uninhibitable and catalitycally inactive GSK3beta forms inhibit the transcriptional activity of a fusion protein containing E2F1 transactivation domain. Both forms of GSK3beta inhibit E2F1 with similar efficiency. Interestingly the effect was independent of the mutation of serine 403 and threonine 433 to alanine. This suggests that this transcriptional modulation is independent of GSK3beta kinase activity and phosphorylation state of serine 403 and threonine 433. The re-targeting of these GSK3beta forms to the nucleus results in a higher capacity to regulate E2F1 transcriptional activity. Depletion of the levels of GSK3beta protein using siRNA activates E2F1 transcriptional activity. The data presented in this study offer a new mechanism of regulation of E2F1 by direct binding of GSK3beta to its transactivation domain.

Cell Line↗
PubMed2006

Regulation of Akt/PKB by phosphatidylinositol 3-kinase-dependent and -independent pathways in B-cell chronic lymphocytic leukemia cells: role of protein kinase C{beta}.

Apoptosis of B cell chronic lymphocytic leukemia (B-CLL) cells is regulated by the PI-3K-Akt pathway. In the present work, we have analyzed the mechanisms of Akt phosphorylation in B-CLL cells. Freshly isolated cells present basal Akt phosphorylation, which is PI-3K-dependent, as incubation with the PI-3K inhibitor LY294002 decreased Ser-473 and Thr-308 phosphorylation in most samples analyzed (seven out of 10). In three out of 10 cases, inhibition of protein kinase C (PKC) inhibited basal Akt phosphorylation. Stromal cell-derived factor-1alpha, IL-4, and B cell receptor activation induced PI-3K-dependent Akt phosphorylation. PMA induced the phosphorylation of Akt at Ser-473 and Thr-308 and the phosphorylation of Akt substrates, independently of PI-3K in B-CLL cells. In contrast, PKC-mediated phosphorylation of Akt was PI-3K-dependent in normal B cells. Finally, a specific inhibitor of PKCbeta blocked the phosphorylation and activation of Akt by PMA in B-CLL cells. Taken together, these results suggest a model in which Akt could be activated by two different pathways (PI-3K and PKCbeta) in B-CLL cells.

Apoptosis↗
PubMed2006

A biased median filtering algorithm for segmentation of intestinal cell gland images.

In this paper, we introduce a biased median filtering image segmentation algorithm for intestinal cell glands consisting of goblet cells. While segmentation of individual cells are generally based on the dissimilarities in intensities, textures, and shapes between cell regions and background, the proposed segmentation algorithm of intestine cell glands is based on the differences in cell distributions. The intestine cell glands consist of goblet cells that are distributed in the chain-organized patterns in contrast to the more randomly distributed nongoblet cells scattered in the bright background. Four biased median filters with long rectangular windows of identical dimension, but different orientations, are designed based on the shapes and distributions of cells. Each biased median filter identifies a part of gland segments in a particular direction. The complete gland regions are the combined responses of the four biased median filters. A postprocessing procedure is designed to reduce the defects that may occur when glands are located very close together and to narrow the gapping areas because of the thin distribution of goblet cells. Segmentation results of real intestinal cell gland images are provided to show the effectiveness of the proposed algorithm.

Algorithms↗
PubMed2006

MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-lived CD5(+) B lymphocytes. Several drugs currently used in the therapy of B-CLL act, at least partially, through activation of the p53 pathway. Recently, nongenotoxic small-molecule activators of p53, the nutlins, have been developed that inhibit p53-MDM2 binding. We have investigated the antitumor potential of nutlin-3 in B-CLL and find that it can activate the p53 pathway and effectively induce apoptosis in cells with wild-type p53, including cells with dysfunctional ataxia telangiectasia mutated, but not mutant p53. Nutlin-3 stabilized p53 and induced p53 target genes, including MDM2, p21(CIP1), PUMA, BAX, PIG3, and WIG1. Nutlin-3 synergized with the genotoxic drugs doxorubicin, chlorambucil, and fludarabine, but not with acadesine, which induces p53-independent apoptosis. Normal human T cells showed lower sensitivity to nutlin-3 than B-CLL cells and no synergism with the genotoxic drugs. These results suggest that MDM2 antagonists alone or in combination with chemotherapeutic drugs may offer a new treatment option for B-CLL.

Antigens, CD↗
PubMed2006

Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells.

OBJECTIVE: Antiapoptotic Bcl-2 is overexpressed in most cases of chronic lymphocytic leukemia (CLL). The inhibition of the antiapoptotic Bcl-2 proteins is an attractive strategy for either restoring normal apoptotic process in cancer cells or making these cells more susceptible to conventional chemotherapy. We studied the effect of Bcl-2 inhibitors on the viability of cells from CLL and other mature B-cell neoplasms. MATERIALS AND METHODS: We studied the cytotoxic effects of four nonpeptidic cell-permeable Bcl-2 inhibitors (HA14-1, antimycin A, GX15-003, and GX15-070) on B cells from patients with CLL, mantle cell lymphoma (MCL), and splenic marginal zone lymphoma (SMZL). Moreover, we analyzed the effect of these inhibitors in combination with fludarabine or chlorambucil. RESULTS: HA14-1 induced apoptosis with an EC50 lower than 50 microM in 26 of the 36 CLL samples analyzed. The mean EC50 for these sensitive patients was 23 +/- 2 microM. Antimycin A induced apoptosis in 13 of the 18 CLL samples analyzed. Both HA14-1 and antimycin A induced cytochrome c release from mitochondria and caspase-3 activation. Moreover, HA14-1 induced apoptosis in peripheral cells from MCL and SMZL. HA14-1 also induced apoptosis in CLL samples with alterations in p53 or ATM. Finally, GX compounds induced apoptosis in B cells from 9 of the 11 CLL samples tested. The combination of either HA14-1, antimycin A, or GX compounds with fludarabine or chlorambucil had additive cytotoxic effects on CLL cells. CONCLUSION: Bcl-2 inhibitors induce apoptosis in CLL cells ex vivo and could be used in CLL as monotherapy or given in combination with current chemotherapy.

Antimycin A↗
PubMed2006

Late recurrent pulmonary typical carcinoid tumor: case report and review of the literature.

Carcinoid tumors are uncommon pulmonary neoplasms. They are classified histologically as either atypical or typical. Atypical carcinoids are aggressive malignancies that require radical surgical resection and have a guarded prognosis with a propensity to metastasize and recur. Typical carcinoids are low-grade malignancies with relatively less metastatic or recurring potential and are usually treated with simple excision. Recurrence of a typical pulmonary carcinoid tumor more than a decade after initial resection is very rare. A patient with recurrence of a typical carcinoid tumor 11 years after resection of the primary lesion with one involved lymph node is reported here. Late recurrences are rare in both atypical and typical varieties, but are much more common in atypical carcinoids. The patient reported here represents the fifth case of recurrence of a typical carcinoid tumor more than ten years after resection. This suggests that, after resection of a typical carcinoid neoplasm, patients should be monitored carefully, especially if lymph node metastases are present at the time of surgery.

Aged, 80 and over↗
PubMed2006

Automatic image segmentation with linear clustering for quantification of neointimal formation after surgical vein grafting.

OBJECTIVE: To identify extracellular matrix deposition on combined Masson elastin stains from cross-sectional, fixed vein grafts. STUDY DESIGN: Source vectors from RGB components of color images are transformed into new vectors with most of the energy concentrated in fewer coefficients based on the eigenvalues and eigenvectors of their co-variance matrix so their dimension can be reduced for efficient computation and analysis. The vectors are distributed in a triangular shape in which most vectors are located in a long, narrow strip that can be approximated by a straight line while a separate group of vectors from collagen areas form a loose cluster away from the line. An iterative procedure has been developed for the representative vectors in the 2 centroids for linear and circular clusters. The linear centroid consists of all vectors in a straight line, and the centroid of the circular cluster is a single vector. Vector classification is based on the measure of its distance to each of the 2 centroids. RESULTS: The automatic segmentation of the collagen content pixels in green-blue matches the image background color. CONCLUSION: The procedure automatically quantifies and characterizes the neointimal deposition after surgical vein grafting in mice.

Algorithms↗
PubMed2005

Respiratory failure secondary to organizing pneumonia in a patient with membranoproliferative glomerulonephritis and lung haemorrhage.

We report the case of a woman with membranoproliferative glomerulonephritis type I who presented with acute respiratory failure secondary to alveolar haemorrhage. The persistence of the respiratory failure, once the alveolar haemorrhage had ceased, was apparently due to diffuse alveolar damage in organization. The recognition of this proliferative reaction through the performance of transbronchial biopsy allowed the initiation of a correct treatment with which a favourable response was obtained.

Cryptogenic Organizing Pneumonia↗
PubMed2005

Obesity and the incidence of chronic diseases in Spain: a seemingly unrelated probit approach.

Western societies can reduce avoidable mortality and morbidity by better understanding the relationship between obesity and chronic disease. This paper examines the empirical association between obesity and the incidence of heart disease, diabetes, hypertension, and elevated cholesterol. We analyze a broadly representative Spanish dataset, the 1999 Survey on Disabilities, Impairments and Health Status, using a health production theoretical framework together with a seemingly unrelated probit model approach that controls for unobserved heterogeneity and endogeneity. Its findings provide evidence of a positive and significant, although specification-dependent, association between obesity and the prevalence of all chronic illness examined.

Adolescent↗
PubMed2005

Segmentation of microscopic images of small intestinal glands with directional 2-D filters.

We present an image segmentation algorithm for small intestinal glands consisting of goblet cells that are evenly distributed and arranged in parallel at the base. Making use of the properties of the chain distribution of the goblet cells, directional 2-dimensional (2-D) linear filters with different orientations were designed to enhance the rims of the intestinal glands. Segmentations are based on the combined responses of the multiple zero-phase directional 2-D linear filters. For comparisons, outputs of combined directional filters are shown along with those of the comparable nondirectional Gaussian filters. Segmentation results of small intestinal glands of both normal and cancer cases are provided.

Algorithms↗
PubMed2004

Characterization of ovarian nuclei with the parameter of power ratio.

The nucleoli and chromatin clumps of ovarian cells contain important features in discriminating malignant cells from normal ones. In geometric properties, the ovarian nucleoli and chromatin clumps appear as irregularly shaped dark spots in the nuclear images from specimens immunohistochemically stained with antibody to Mib-1. Malignant cells often have more active and larger nucleoli and chromatin clumps. However, estimating the size of the nucleoli or chromatin clumps is a difficult task since it is not easy to recognize and accurately separate the regions of nucleoli and chromatin clumps from the rest of the nuclei that are highly irregular and variant in contents and intensities. In this paper, we develop a method to derive a parameter called power ratio that is proportionally related to the size of nucleoli and chromatin clumps based on an ideal nuclear model without the region segmentation of nucleoli or chromatin clumps. Results of characterization of the parameter and comparison between malignant and normal cells are provided.

Algorithms↗
PubMed2004

Gibberellins repress photomorphogenesis in darkness.

Plants undergo two different developmental programs depending on whether they are growing in darkness (skotomorphogenesis) or in the presence of light (photomorphogenesis). It has been proposed that the latter is the default pathway followed by many plants after germination and before the seedling emerges from soil. The transition between the two pathways is tightly regulated. The conserved COP1-based complex is central in the light-dependent repression of photomorphogenesis in darkness. Besides this control, hormones such as brassinosteroids (BRs), cytokinins, auxins, or ethylene also have been shown to regulate, to different extents, this developmental switch. In the present work, we show that the hormone gibberellin (GA) widely participates in this regulation. Studies from Arabidopsis show that both chemical and genetic reductions of endogenous GA levels partially derepress photomorphogenesis in darkness. This is based both on morphological phenotypes, such as hypocotyl elongation and hook and cotyledon opening, and on molecular phenotypes, such as misregulation of the light-controlled genes CAB2 and RbcS. Genetic studies indicate that the GA signaling elements GAI and RGA participate in these responses. Our results also suggest that GA regulation of this response partially depends on BRs. This regulation seems to be conserved across species because lowering endogenous GA levels in pea (Pisum sativum) induces full de-etiolation in darkness, which is not reverted by BR application. Our results, therefore, attribute an important role for GAs in the establishment of etiolated growth and in repression of photomorphogenesis.

Arabidopsis↗
PubMed2004

Extranodal follicular dendritic cell tumor of the tonsil: report of a diagnostic pitfall and literature review.

Follicular dendritic cell tumor (FDCT) usually arises in the dendritic reticulum cells of the lymph nodes. Extranodal cases are rare; only 24 cases have been reported in the head and neck region, and most are in the oropharynx. Nine cases of primary FDCT of the tonsil have been reported in English-language literature, to which we add the 10th case. This 77-year-old white woman presented with a tonsillar mass that was misdiagnosed as squamous cell carcinoma. She underwent neoadjuvant radiotherapy plus combined oropharyngeal and mandibular resection with radical neck dissection. Eight years later, she presented with dyspnea and was found to have a lung mass with hilar lymphadenopathy. A biopsy specimen was taken from the hilar lymph nodes, and histologic analysis yielded results similar to those found in the original tumor. Immunohistochemical analysis confirmed that FDCT was present at both sites. We wish to highlight this potential diagnostic pitfall because the treatment and prognosis for FDCT are vastly different from the treatment and prognosis for squamous cell carcinoma of the tonsil.

Aged↗
PubMed2004

Aspirin-induced apoptosis in jurkat cells is not mediated by peroxisome proliferator-activated receptor delta.

Nonsteroidal antiinflammatory drugs may induce apoptosis via inhibition of peroxisome proliferator-activated receptor delta (PPARdelta) activity. Here we analyze the role of PPARdelta in aspirin-induced apoptosis of Jurkat cells, which, together with other lymphoid cell lines, express PPARdelta mRNA. Aspirin increased PPARdelta mRNA levels in Jurkat cells, but decreased the activity of both PPARdelta and PPARalpha/gamma, assayed using the luciferase reporter constructs DRE and ACO, respectively. The DNA binding of PPARdelta was not affected by 10 mM aspirin, which induces apoptosis in Jurkat cells. Moreover, neither addition of a specific ligand of PPARdelta nor transient transfection of PPARdelta expression vectors protected Jurkat cells from aspirin-induced apoptosis. These results indicate that PPARdelta is not involved in aspirin-induced apoptosis. Therefore, the mechanism by which aspirin mediates cell death in Jurkat cells remains unknown.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Transcriptional and translational control of Mcl-1 during apoptosis.

Mcl-1 is an antiapoptotic member of the Bcl-2 family whose protein and mRNA have a short half-life. In this report, we studied the changes in Mcl-1 protein and mRNA expression induced by staurosporine and aspirin. Both drugs induced apoptosis in Jurkat cells and reduced the levels of Mcl-1 protein. The caspase inhibitor Z-VAD.fmk and the proteasome inhibitor MG132 partially protected Mcl-1 from decay, indicating that both caspase-dependent and proteasome pathways are involved during apoptosis. Staurosporine also reduced Mcl-1 mRNA levels and this reduction was mostly caspase-dependent. In addition, staurosporine reduced the transcriptional activity of the Mcl-1 promoter fused to a luciferase gene reporter more than actinomycin D, a general inhibitor of transcription. Thus, we conclude that staurosporine down-regulates Mcl-1 mRNA levels by inhibiting transcription in a caspase-dependent manner and reduces Mcl-1 protein levels by a caspase-independent post-transcriptional mechanism. In contrast aspirin, at doses and times that induced loss of viability and decay of Mcl-1 protein, had no effect on Mcl-1 mRNA levels. Aspirin rapidly inhibited de novo protein synthesis before caspase activation. Moreover, the translational factor eIF2alpha was transiently phosphorylated and therefore inhibited very soon after aspirin treatment. Aspirin also inhibited the luciferase reporter activity of several attached promoter constructs, but it did not affect the luciferase activity of a construct containing an internal ribosome entry site (IRES) in its mRNA 5(')UTR. We conclude that staurosporine inhibits transcription and translation, whereas aspirin only inhibits cap-dependent translation. Treatment with cycloheximide, at doses that inhibit protein synthesis without affecting cell viability, also induced Mcl-1 protein decay. Mcl-1 disappearance might be necessary but not sufficient for the induction of apoptosis by staurosporine and aspirin. A model for the control of Mcl-1 during drug-induced apoptosis is presented.

Apoptosis↗