Biomedical subjects
J Casanova
Publications and source records attributed to J Casanova.
Antimicrobial activity and chemical composition of the bark oil of Croton stellulifer, an endemic species from S. Tomé e Príncipe.
The composition and the antimicrobial activity of the bark oil of Croton stellulifer, an endemic and rare species of these islands (S. Tomé and Príncipe) are reported. Analysis was carried out by GC, GC/MS and 13C-NMR. The major constituents were alpha-phellandrene (15.4-18.6%), p-cymene (14.4-17.7%), linalool (12.0-12.6%) and alpha-pinene (8.1-9.1%). Kessane, a sesquiterpenoid oxide, not yet reported in the genus Croton, was identified by NMR. The essential oil of C. stellulifer was active against both bacterial and fungal strains, except Aspergillus niger.
The GAGA factor of Drosophila interacts with SAP18, a Sin3-associated polypeptide.
SAP18, a polypeptide associated with the Sin3-HDAC co-repressor complex, was identified in a yeast two-hybrid screen as capable of interacting with the Drosophila GAGA factor. The interaction was confirmed in vitro by glutathione S-transferase pull-down assays using recombinant proteins and crude SL2 nuclear extracts. The first 245 residues of GAGA, including the POZ domain, are necessary and sufficient to bind dSAP18. In polytene chromosomes, dSAP18 and GAGA co-localize at a few discrete sites and, in particular, at the bithorax complex where GAGA binds some silenced polycomb response elements. When the dSAP18 dose is reduced, flies heterozygous for the GAGA mutation Trl67 show the homeotic transformation of segment A6 into A5, indicating that GAGA-dSAP18 interaction contributes to the functional regulation of the iab-6 element of the bithorax complex. These results suggest that, through recruitment of the Sin3-HDAC complex, GAGA might contribute to the regulation of homeotic gene expression.
The 3-month clinical response to intravesical therapy as a predictive factor for progression in patients with high risk superficial bladder cancer.
PURPOSE: We analyzed the 3-month clinical response to intravesical therapy as a factor predictive of progression in patients with high risk superficial bladder cancer. MATERIAL AND METHODS: We evaluated 191 patients with high risk superficial bladder cancer, 111 with secondary or associated bladder carcinoma in situ and 80 with stage T1 grade 3 disease who were treated with intravesical therapy. We considered only clinically complete and no responses at the 3-month endoscopic study. To determine the predictive value of the 3-month clinical response we differentiated progression into superficial and invasive types. RESULTS: At a median followup of 73 months 91 patients (47.6%) had progression, which was superficial in 48 (25. 1%) and invasive in 43 (22.5%). Invasive progression was associated with significantly higher cause specific mortality than superficial progression (p = 0). In the latter cases cause specific mortality was higher than in those without progression (p = 0.001). Although cystectomy significantly decreased the cause specific mortality rate in patients with invasive progression (p = 0.0001), this rate was high at 46.3%. Univariate and multivariate analyses revealed that the 3-month clinical response was a significant predictive factor for progression. Moreover, stratifying this variable showed that this response was the only independent factor predictive of invasive progression in cases of no response with stage T1 grade 3 tumor, bladder carcinoma in situ, or prostate mucosa or duct involvement (p = 0). In our series 41 patients (21.5%) did not respond after intravesical therapy at the 3-month evaluation, including 29 with stage T1 grade 3 disease, bladder carcinoma in situ, or prostate mucosa or duct involvement. Progression in 24 of these 29 patients (82.3%) was classified as invasive in 21 (73.6%). CONCLUSIONS: Invasive progression threatens the cause specific survival of patients with high risk superficial bladder cancer even when cystectomy is performed. The 3-month clinical response was an excellent predictive factor for invasive progression. Early cystectomy should be considered when stage T1 grade 3 tumor, bladder carcinoma in situ, or prostate mucosa or duct involvement is present at the 3-month clinical evaluation.
EGF signalling regulates cell invagination as well as cell migration during formation of tracheal system in Drosophila.
The Drosophila tracheal system is a network of epithelial tubes that arises from the tracheal placodes, lateral clusters of ectodermal cells in ten embryonic segments. The cells of each cluster invaginate and subsequent formation of the tracheal tree occurs by cell migration and fusion of tracheal branches, without cell division. The combined action of the Decapentaplegic (Dpp), Epidermal growth factor (EGF) and breathless/branchless pathways are thought to be responsible for the pattern of tracheal branches. We ask how these transduction pathways regulate cell migration and we analyse the consequences on cell behaviour of the Dpp and EGF pathways. We find that rhomboid (rho) mutant embryos display defects not only in tracheal cell migration but also in tracheal cell invagination unveiling a new role for EGF signalling in the formation of the tracheal system. These results indicate that the transduction pathways that control tracheal cell migration are active in different steps of tracheal formation, beginning at invagination. We discuss how the consecutive steps of tracheal morphogenesis might affect the final branching pattern.
Rapid screening for organochlorine and organophosphorus pesticides in milk using C18 and graphitized carbon black solid phase extraction cleanup.
A rapid, multiresidue, solid phase extraction (SPE) technique for the isolation and gas chromatographic determination of organochlorine and moderately polar organophosphorus pesticide residues in milk is described. Milk is sonicated with an acetonitrile-acetone-methanol mixture and centrifuged. The supernatant is subjected to a cleanup using both C18 and graphitized carbon black SPE columns. The pesticide residues are determined by gas chromatography with electron capture and flame photometric detection. The method required minimal volumes of solvent and resulted in the production of minimal volumes of hazardous waste.
Effectiveness of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer: short and long-term followup.
PURPOSE: We analyze the impact of a single mitomycin C instillation in patients with low risk superficial bladder cancer with short and long-term followup. MATERIALS AND METHODS: A total of 131 patients with low risk superficial bladder cancer were included in a prospective randomized controlled trial. All patients had a 3 cm or less single, papillary, primary or recurrent tumor and were disease-free for more than 1 year. Patients with muscular invasion, G3 tumor or bladder carcinoma in situ on pathological examination were excluded from study. The tumor was completely resected before patients were randomized into 2 arms of no further treatment (control group) and a single immediate instillation of 30 mg mitomycin C (mitomycin C group). Recurrences were considered early within the first 2 years of followup. RESULTS: At 24-month followup the recurrence-free interval was significantly increased, and recurrence, and recurrence and tumor per year rates were decreased in the mitomycin C compared to the control group. However, at long-term followup these differences were not statistically significant and the recurrence-free interval curves were parallel. A shorter hospital stay and catheterization period were noted in the mitomycin C group compared to the control group, which were not significant. Early recurrences were concentrated in the first year in the control but not in the mitomycin C group. A significant relationship between early and late recurrences was found in the mitomycin C but not in the control group. CONCLUSIONS: Our analysis confirms the positive effect of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer. This benefit is limited to early recurrence and is not maintained with long-term followup. Thus, this approach is an alternative to observation or endovesical chemotherapy. Our study also suggests that cell implantation as a mechanism of early recurrence can be controlled with a single mitomycin C instillation.
Role of the conserved C-terminal region of thyroid hormone receptor-alpha in ligand-dependent transcriptional activation.
The ligand binding domain (LBD) of thyroid hormone (T3) receptors contains subdomains that participate in transcriptional activation, hormone-relieved repression and dimerization. A sequence conserved within the nuclear receptor superfamily is found at positions 397-405 of the 408-amino acid chicken T3 receptor-alpha (cTR alpha) and is deleted in the related avian v-erbA. Since v-erbA exhibits compromised ligand binding and transcriptional activation, this conserved region may play a role in ligand-dependent transcriptional activation. Transfections reveal that cTR alpha(1-392) and site-directed mutants cTR alpha(L398R) and cTR alpha(F399E) are inactive, while cTR alpha(1-403) displays reduced ligand-dependent transcriptional activity. The loss of transcriptional activity in cTR alpha(1-392) is not caused by impaired DNA binding or receptor dimer formation. Proteolytic protection assays reveal that both transcriptionally active and inactive cTR alpha derivatives undergo T3-mediated conformational changes. Gal4 chimeras containing the final 16, 35 or 44 amino acids of cTR alpha indicate that the conserved C-terminal region does not function as an independent transactivation domain. Our results are consistent with a model in which ligand plays a structural role to position the conserved C-terminal regions of cTR alpha and related receptors in a transcriptionally active conformation.
Feasibility of transurethral resection for muscle infiltrating carcinoma of the bladder: long-term followup of a prospective study.
PURPOSE: We analyzed the long-term results of radical transurethral resection for the treatment of a large series of patients with muscle infiltrating bladder cancer entered into a prospective study to determine progression predictive factors. MATERIALS AND METHODS: The study included 133 patients with invasive bladder cancer treated by radical transurethral resection who had negative biopsies of the muscle layer of the tumor bed. Followup was more than 5 years for all subjects and more than 10 years in 59 (44.4%). A comparative nonrandomized study was performed of a control group of 76 patients with invasive pathological stage pT2-3a, N0-3 bladder cancer treated by cystectomy. In those patients treated by radical transurethral resection univariate and multivariate analyses were performed to establish clinical progression predictive factors. RESULTS: At 5 and 10 years of followup cause specific survival rates were 80.5 and 74.5%, and bladder preservation rates were 82.7 and 79.6%, respectively. No significant difference was noted in terms of cause specific survival, with respect to the control group. The initial presence of associated bladder carcinoma in situ was the only independent progression predictive factor. CONCLUSIONS: For patients with invasive bladder cancer radical transurethral resection is justified when the tumor is clinically limited to the muscular layer and when all biopsies of the periphery and depth of the tumor bed show muscular tissue negative for tumor cells. Patients with initial associated bladder carcinoma in situ should not be excluded from this treatment but endovesical bacillus Calmette-Guerin immunotherapy should be administered and a closer followup is recommended.
Dissecting the mechanism of torso receptor activation.
Regulated activation of receptor tyrosine kinases depends both on the presence of the receptors at the cell surface and on the availability of their ligands. In Drosophila the torso (tor) tyrosine kinase receptor is distributed along the surface of the embryo but it is only activated at the poles by a diffusible extracellular ligand generated at each pole which is trapped by the receptor, thereby impeding further diffusion. However, it is not well understood how this signal is generated, although it is known to depend on the activity of many genes such as torso-like (tsl) and trunk (trk). To further investigate the mechanism involved in the local activation of the tor receptor we have altered the normal expression of the tsl protein by generating females in which the tsl gene is expressed in the oocyte under the control of the tor promoter rather than in the ovarian follicle cells. Analysis of the phenotypes generated by this hybrid gene and its interactions with mutations in other genes in the pathway has enabled us to further dissect the mechanism of tor receptor activation and to define more precisely the role of the different genes acting in this process.
[Partial pericardectomy using videothoracoscopy].
OBJECTIVE: The aim of this study is to assess the validity of videothoracoscopy in the treatment of chronic pericardial effusions. STUDY PATIENTS: We studied 13 consecutive patients with chronic pericardial effusions and an indication for surgical treatment. The patients, 10 female and 3 male, had a mean age of 48 years (21-72 years). Eleven patients had recurrent pericardial effusion and two patients had anterior mediastinal masses of unknown etiology and a large pericardial effusion. METHODS: A videothoracoscopy was performed in every patient, under general anesthesia with a double-lumen endotracheal tube. The thoracic cavity was inspected, the pericardial effusion was drained and a partial pericardectomy was performed. RESULTS: There was no postoperative mortality or morbidity. Average duration of postoperative thoracic drain and postoperative stay were, 1.2 and 2.4 days respectively. Follow-up ranged from 1 to 48 months (mean 23.3 months). One patient died due to progression of his malignant disease. There were no cases of recurrent pericardial effusions. CONCLUSIONS: Video assisted pericardectomy is a safe technique that should be considered in the treatment of chronic pericardial effusions.
Transesophageal echocardiography on the presurgical and postsurgical evaluation of a coronary arteriovenous fistula.
A 52-year-old man with a symptomatic condition-a huge left coronary artery fistula simulating a cor triatriatum sinister on transthoracic echocardiography-was referred to our center for surgery. Coronary angiography unequivocally established the diagnosis of a left coronary artery fistula and contrast opacification of the right atrium was observed. However, as a result of the size of the fistula, the entry site could not be defined with certainty. A transesophageal echocardiography (TEE) was then performed, and the opening site was clearly identified in the postero-lateral wall of the right atrium. After the surgical treatment transesophageal echocardiography was repeated, and it was confirmed that the surgical treatment had succeeded.
Descending necrotising mediastinitis--successful treatment using a radical approach.
Descending necrotising mediastinitis has been linked with significant morbidity and mortality. We report two recent cases and discuss the surgical management of this serious disease. Complete thoracic drainage was achieved through a median stemotomy, allowing a fast recovery.
ventral veinless, a POU domain transcription factor, regulates different transduction pathways required for tracheal branching in Drosophila.
Cell migration is an important step in a variety of developmental processes in many multicellular organisms. A particularly appropriate model to address the study of cell migration is the tracheal system of Drosophila, whose formation occurs by migration and fusion from clusters of ectodermal cells specified in each side of ten embryonic segments. Morphogenesis of the tracheal tree requires the activity of many genes, among them breathless (btl) and ventral veinless (vvl) whose mutations abolish tracheal cell migration. Activation of the btl receptor by branchless (bnl), its putative ligand, exerts an instructive role in the process of guiding tracheal cell migration. vvl has been shown to be required for the maintenance of btl expression during tracheal tree formation. Here we show that, in addition, vvl is independently required for the specific expression in the tracheal cells of thick veins (tkv) and rhomboid (rho), two genes whose mutations disrupt only particular branches of the tracheal system. Indeed, we show that expression in the tracheal cells of an activated form of tkv, the putative decapentaplegic (dpp) receptor, is able to induce shifts in their migration, asserting the role of the dpp pathway in establishing the branching pattern of the tracheal tree. In addition, by ubiquitous expression of the btl and tkv genes in vvl mutant embryos we show that both genes contribute to vvl function. These results indicate that through activation of its target genes, vvl makes the tracheal cells competent to further signalling and suggest that the btl transduction pathway could collaborate with other transduction pathways also regulated by vvl to specify the tracheal branching pattern.
Synthesis and characterization of metal(II)-8-quinolinsulfonamidato (sa-) complexes (M = Co, Ni, Cu, and Zn). Crystal structure of [Zn(sa)2(NH3)]NH3 complex. Carbonic anhydrase inhibitory properties.
A new sulfonamide, 8-quinolinsulfonamide(Hsa), has been prepared and examined as a chelating agent towards metal(II) ions. The spectroscopic properties of the M(II) sulfonamidato complexes has been studied. The inhibitory properties of the ligand and the synthesised complexes were tested. The crystal structure of the [Zn(sa)2(NH3)].NH3 complex was determined by single-crystal X-ray diffraction. Crystal data of the zinc(II) complex: a = 16.217(4)A, b = 8.041(1)A, c = 15.606(4)A, beta = 95.75(1) degrees, Z = 4, and V = 2024.6(7)A3. The refinement of the structure based on 6047 reflections attained to R = 0.049 and Rw = 0.052. The zinc(II) ion is surrounded by four N atoms of two sulfonamidato ligands and one N atom of an ammonia molecule in an trigonal bipyramid arrangement.
[Videothoracoscopy in the surgical treatment of pneumothorax: report of 46 cases].
We report our 3-years experience with video-thoracoscopy for pneumothorax. Forty-six endoscopies (34 men, 12 women; mean age 27 +/- 9 years) were performed. Patients were under general anesthesia and intubation was selective. The conventional approach was used, with 3 incisions through which the camera and endoscopic instruments were inserted. Results were good in 39 (84.7%) patients. Pneumothorax recurred in 4 (8.7%) patients during the 3 years of follow-up. Thoracotomy was performed in 3 patients, because of lack of lung expansion in 1, persistent leak in another and encapsulated empyema in the third. Mean hospital stay after surgery was 7.3 days. Video-thoracoscopy can be considered a good therapeutic alternative to thoracotomy in the surgical treatment of patients with pneumothorax.
Intrapericardial paraganglioma.
We describe the case of an intrapericardial pheochromocytoma located in the anterior surface of the heart and spreading over the pulmonary trunk. Under cardiopulmonary bypass (CPB) the tumor was removed. "En bloc" resection of the anterior wall of the right ventricular infundibulum and the pulmonary trunk was performed, with implantation of a fresh aortic homograft in the pulmonary position to avoid free pulmonary regurgitation.
Variation in the number of activated torso receptors correlates with differential gene expression.
Activation of receptor tyrosine kinases triggers many developmental decisions, yet we do not understand how activation of a single receptor can be transduced into different cell responses. The torso pathway in Drosophila provides a model to address this issue since it generates more than one response in the embryo. The torso receptor tyrosine kinase is activated at the embryonic poles under the control of trunk, a protein with similarities to several types of extracellular growth factors. Activation of torso is responsible for the development of a variety of structures, whose appearance can be correlated with activation of at least two different genes along the terminal region. In this study we have analyzed mutations in torso and trunk that express low levels of the respective proteins. We show that different amounts of torso or trunk molecules correlate with the expression of different zygotic genes, implicating changes in the number of activated torso molecules as one of the mechanisms defining differential gene expression. We suggest that variation in the number of activated receptors at the cell surface is a general mechanism that leads to differential gene expression and thus the generation of different cell responses.