Biomedical subjects

Francisco Romero

Publications and source records attributed to Francisco Romero.

12 recordsLinked to original sources

PubMed2006

Web-based adaptive training simulator system for cardiac life support.

OBJECTIVE: We introduce a web-based adaptive training simulator system to exercise cardiopulmonary resuscitation skills. Our purpose is to provide emergency physicians with an additional training tool for cardiac life support clinical cases, by integrating an adaptive learning environment with a web-based case simulator. METHODS AND MATERIALS: Adaptive systems reflect some features of the user in the user model and apply this model to adapt various visible aspects of the system to the user. Our system follows a stage-based learning model with several steps to personalize student learning. First, students learn the theory and content of life support and take computerized tests to evaluate their declarative knowledge of these areas. Second, they practice with clinical case examples and complete an exam at the appropriate level of difficulty to assess their practical knowledge. Finally, they train with additional clinical cases. RESULTS AND CONCLUSION: In order to evaluate the usefulness of the system, we used it in two traditional advanced life support courses at the Jaen Hospital in Spain, as an additional and complementary tool within the course. Results show that the use of adaptation techniques can improve student performance.

Advanced Cardiac Life Support↗

PubMed2006

Temporal profile of recanalization after intravenous tissue plasminogen activator: selecting patients for rescue reperfusion techniques.

BACKGROUND AND PURPOSE: Intravenous thrombolysis in stroke achieves arterial recanalization in approximately 50% of cases. Determining temporal profile of recanalization may address patient selection and potential benefits of further rescue reperfusion techniques. METHODS: We studied 179 consecutive intravenous tissue plasminogen activator (t-PA)-treated patients with intracranial artery occlusion. Continuous transcranial Doppler assessed recanalization (none-partial-complete) at 60 minutes (early), 120 minutes (delayed) after t-PA bolus, and 6 hours (late) from symptom onset. Outcomes were determined: National Institutes of Health Stroke Scale (NIHSS; 48-hour NIHSS) and 3-month modified Rankin Scale (mRS). RESULTS: On admission, 68% of patients presented proximal middle cerebral artery occlusion, median NIHSS 17. Early recanalization was complete for 30 patients (17%), partial for 50 (28%), and none for 99 (55%). Delayed recanalization was complete for 56 patients (31%), partial for 39 (22%), and none for 84 (47%). Although early flow improvement was observed in up to 45% of patients, only 19% of patients with persistent occlusion (11% of total) presented delayed recanalization (odds ratio [OR] delayed/early recanalization, 0.16; 95% CI, 0.085 to 0.304; P<0.001). Among patients with persistent occlusion at 2 hours, only 13 (7% of total) presented late flow improvement (OR late/early recanalization, 0.09; 95% CI, 0.043 to 0.196; P<0.001). The few patients with late recanalization presented comparable median 48-hour NIHSS to those with early/delayed recanalization (3 versus 4.5; P=0.9) and much lower than those with persistent occlusion after 6 hours (3 versus 15; P=0.005). At 3 months, the rate of mRS < or =2 was not statistically different between patients with early/delayed versus late recanalization (55% versus 86%; P=0.12) but was lower if occlusion persisted 6 hours after onset (22%; P<0.001). CONCLUSIONS: The majority of t-PA-induced recanalizations occur during the first hour after treatment. Recanalizations during the following hours are rare but still related to clinical improvement if achieved within 6 hours from onset. Rescue reperfusion techniques should be considered if flow improvement is not observed 60 minutes after t-PA bolus.

Adult↗

PubMed2006

Protein phosphatase 2A stabilizes human securin, whose phosphorylated forms are degraded via the SCF ubiquitin ligase.

Sister chromatid segregation is triggered at the metaphase-to-anaphase transition by the activation of the protease separase. For most of the cell cycle, separase activity is kept in check by its association with the inhibitory chaperone securin. Activation of separase occurs at anaphase onset, when securin is targeted for destruction by the anaphase-promoting complex or cyclosome E3 ubiquitin protein ligase. This results in the release of the cohesins from chromosomes, which in turn allows the segregation of sister chromatids to opposite spindle poles. Here we show that human securin (hSecurin) forms a complex with enzymatically active protein phosphatase 2A (PP2A) and that it is a substrate of the phosphatase, both in vitro and in vivo. Treatment of cells with okadaic acid, a potent inhibitor of PP2A, results in various hyperphosphorylated forms of hSecurin which are extremely unstable, due to the action of the Skp1/Cul1/F-box protein complex ubiquitin ligase. We propose that PP2A regulates hSecurin levels by counteracting its phosphorylation, which promotes its degradation. Misregulation of this process may lead to the formation of tumors, in which overproduction of hSecurin is often observed.

Animals↗

PubMed2004

In vivo immunomodulation by Mycoplasma fermentans membrane lipoprotein.

The immunomodulatory effects of Mycoplasma fermentans-derived membrane lipoprotein (LAMPf) in BALB/c mice were examined. When injected intraperitoneally into mice, LAMPf induced a transitory splenomegaly followed by a suppression of the spleen cell proliferation in response to concanavalin A, whereas responses to lipopolysaccharide and to LAMPf were unchanged. The intravenous injection of a large dose of LAMPf induced leukopenia and granulocyte-macrophage colony-stimulating factor (GM-CSF) activity in serum. A synthetic analogue of its N-terminal lipopeptide with ability to activate macrophages (MALP-2) was also able to induce GM-CSF in serum. Interestingly, GM-CSF induction by a low dose of MALP-2 was not associated with significant leukopenia. These data revealed that the in vitro moduline properties of mycoplasmal lipoproteins and lipopeptides correlate with interesting in vivo immunomodulatory effects.

Animals↗

PubMed2004

Securin is a target of the UV response pathway in mammalian cells.

All eukaryotic cells possess elaborate mechanisms to protect genome integrity and ensure survival after DNA damage, ceasing proliferation and granting time for DNA repair. Securin is an inhibitory protein that is bound to a protease called Separase to inhibit sister chromatid separation until the onset of anaphase. At the metaphase-to-anaphase transition, Securin is degraded by the anaphase-promoting complex or cyclosome, and Separase contributes to the release of cohesins from the chromosome, allowing for the segregation of sister chromatids to opposite spindle poles. Here we provide evidence that human Securin (hSecurin) has a novel role in cell cycle arrest after exposure to UV light or ionizing radiation. In fact, irradiation downregulated the level of hSecurin protein, accelerating its degradation via the proteasome and reducing hSecurin mRNA translation, but the presence of hSecurin is necessary for cell proliferation arrest following UV treatment. Moreover, an alteration of UV-induced hSecurin downregulation could lead directly to the accumulation of DNA damage and the subsequent development of malignant tumors.

Animals↗

PubMed2004

[Renal angiomyolipoma with arteriovenous fistula causing retroperitoneal hematoma. Case report].

OBJECTIVES: To report the case of a female patient with ultrasound diagnosis of great left retroperitoneal hematoma admitted to the hospital for diagnostic workup and treatment. METHODS: 39-year-old patient presenting with intense epigastric pain irradiated to both flanks. Hematuria was not present. CT scan and arteriography led to the diagnosis of angiomyolipoma with arteriovenous fistula and subcapsular hematoma. Selective embolization was carried out. CONCLUSIONS: Hamartomas account for 3% of kidney tumors in adults; they are composed of 3 mesodermal tissues, including blood vessels. The lack of elastic membrane in their arteries favours aneurysm development.

Adult↗

PubMed2003

The effect of FITA mutations on the symbiotic properties of Sinorhizobium fredii varies in a chromosomal-background-dependent manner.

nodD1 of Sinorhizobium fredii HH103, which is identical to that of S. fredii USDA257 and USDA191, repressed its own expression. Spontaneous flavonoid-independent transcription activation (FITA) mutants of S. fredii HH103 M (=HH103 RifR pSym::Tn 5-Mob) showing constitutive expression of nod genes were isolated. No differences were found among soybean cultivar Williams plants inoculated with FITA mutants SVQ250 or SVQ253 or with the parental strain HH103M. Soybean plants inoculated with mutant SVQ255 formed more nodules, and those inoculated with mutant SVQ251 had symptoms of nitrogen starvation. Sequence analyses showed that all of the FITA mutants carried a point mutation in their nodD1 coding region. Mutants SVQ251 and SVQ253 carried the same mutation, but only the former was symbiotically impaired, which indicated the presence of an additional mutation elsewhere in the genome of mutant SVQ251. Mutants SVQ251 and SVQ255 were outcompeted by the parental strain for nodulation of soybean cultivar Williams. The symbiotic plasmids of mutants SVQ251 and SVQ255 (pSym251 and pSym255, respectively) and that (pSymHH103M) of the parental strain were transferred to pSym-cured derivatives of S. fredii USDA192 and USDA193 (USDA192C and USDA193C, respectively). Soybean responses to inoculation with S. fredii USDA192C and USDA193C transconjugants carrying pSym251 and pSymHH103M were not significantly different, whereas more nodules were formed after inoculation with transconjugants carrying pSym255. Only transconjugant USDA192C(pSym255) produced a significant increase in soybean dry weight.

Bacterial Proteins↗

PubMed2003

Immunomodulation by Yersinia enterocolitica: comparison of live and heat-killed bacteria.

This study compared the immunomodulating properties of viable and killed Yersinia enterocolitica O9 in BALB/c mice. At 10 days after infection by the intragastric route, ex vivo assays showed a suppression of spleen cell proliferation in response to Salmonella lipopolysaccharide, concanavalin A and heat-killed yersiniae. Mice infected with Y. enterocolitica O9 for 10 days resisted the challenge with a lethal dose of Listeria monocytogenes. In contrast, intravenous administration of heat-killed yersiniae did not modify the ability of spleen cells to proliferate in response to lipopolysaccharide or concanavalin A, and proliferation in response to killed yersiniae was significantly increased. By 3 days after administration of a single dose of heat-killed yersiniae, the resistance of mice to L. monocytogenes challenge was significantly increased. Our findings show profound differences in immunomodulation by viable and heat-killed yersiniae, but suggest that killed yersiniae retain interesting immunomodulating properties.

Animals↗

PubMed2003

IB-00208, a new cytotoxic polycyclic xanthone produced by a marine-derived Actinomadura. I. Isolation of the strain, taxonomy and biological activites.

A new compound, IB-00208, has been isolated from the fermentation broth of an actinomycete isolated from a marine environment. The strain was identified as Actinomadura sp. by its chemical and phylogenetic characteristics. The compound shows cytotoxic activity on tumor cell lines and bactericidal activity against gram-positive bacteria.

Actinomycetales↗

PubMed2002

Expression of hpttg proto-oncogene in lymphoid neoplasias.

Pituitary tumor-transforming gene (pttg) is a distinct proto-oncogene which is expressed in certain normal tissues with high proliferation rate and in a variety of tumors. PTTG is the vertebrate analog of yeast securins Pds1 and Cut2 with a key role in the regulation of sister chromatid separation during mitosis. Impairment of PTTG regulated functions is expected to lead to chromosomal instability and aneuploidy. Human pttg (hpttg) is abundantly expressed in Jurkat T lymphoblastic lymphoma cells but not in normal peripheral blood leukocytes. To obtain additional data on the potential role of hpttg in lymphomagenesis we selected 150 cases of lymphoid tumors for the assessment of hpttg expression in tumor tissues. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissues revealed hPTTG in 38.8% of B-cell lymphomas, 70.2% of T-cell lymphomas, and 73.1% of Hodgkin's lymphomas. Among B-cell lymphomas, the most frequently immunostained tumors were plasma cell tumors, diffuse large cell lymphomas, and follicle center cell lymphomas. In Hodgkin's disease, immunoreactivity was mainly noted in Reed-Sternberg cells. In conclusion, the frequent overexpression of hpttg in many histological subtypes of lymphoma suggests the involvement of this proto-oncogene in lymphomagenesis.

Blotting, Northern↗

PubMed2002

Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis.

The gene PTTG1 (encoding the pituitary tumor-transforming 1 protein) is overexpressed in several different tumor types, is tumorigenic in vivo and shows transcriptional activity. The PTTG1 protein is cell-cycle regulated and was identified as the human securin (a category of proteins involved in the regulation of sister-chromatid separation) on the basis of biochemical similarities with the Pds1p protein of budding yeast and the Cut2p protein of fission yeast. To unravel the function of human securin in oncogenesis, we carried out a phage-display screening to identify proteins that interact with securin. Notably, we isolated the p53 tumor suppressor. Pull-down and co-immunoprecipitation assays demonstrated that p53 interacts specifically with securin both in vitro and in vivo. This interaction blocks the specific binding of p53 to DNA and inhibits its transcriptional activity. Securin also inhibits the ability of p53 to induce cell death. Moreover, we observed that transfection of H1299 cells with securin induced an accumulation of G2 cells that compensated for the loss of G2 cells caused by transfection with p53. We demonstrated the physiological relevance of this interaction in PTTG1-deficient human tumor cells (PTTG1(-/-)): both apoptotic and transactivating functions of p53 were potentiated in these cells compared to parental cells. We propose that the oncogenic effect of increased expression of securin may result from modulation of p53 functions.

Apoptosis↗

PubMed2002

Thrombolysis-related hemorrhagic infarction: a marker of early reperfusion, reduced infarct size, and improved outcome in patients with proximal middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: The role of early and delayed recanalization after thrombolysis in the development of hemorrhagic transformation (HT) subtypes remains uncertain. We sought to explore the association between the timing of recanalization and HT risk in patients with proximal middle cerebral artery (MCA) occlusion treated with intravenous recombinant tissue plasminogen activator (rtPA) <3 hours of stroke onset and to investigate the relationship between HT subtypes, infarct volume, and outcome. METHODS: Thirty-two patients with acute stroke caused by proximal MCA occlusion treated with rtPA <3 hours of symptom onset were prospectively studied. Serial transcranial Doppler examinations were performed on admission and at 6, 12, 24, and 48 hours. Presence and type of HT were assessed on CT at 36 to 48 hours. Modified Rankin scale was used to assess outcome at 3 months. RESULTS: Early and delayed recanalization was identified in 17 patients (53.1%) and 8 patients (25%), respectively. HT was detected in 14 patients (43.7%): 4 (12.5%) with hemorrhagic infarction (HI1), 5 (15.6%) with HI2, 3 (9.3%) with parenchymal hematoma (PH1), and 2 (6.8%) with PH2. Distribution of HT subtypes differed significantly (P=0.025), depending on the time to artery reopening. Eight of 9 (89%), 1 of 5 (20%), and 8 of 18 (44.4%) with HI1-HI2, with PH1-PH2, and without HT, respectively, recanalized in <6 hours. Delayed recanalization was observed in 1 patient with HI1-HI2 (11%), 4 with PH1-PH2 (80%), and 3 without HT (16.6%). Neurological improvement was significantly (P<0.001) more frequent in patients with HI1-HI2 (88%) than in those without HT (39%). Infarct volume was significantly (P<0.031) lower in patients with HI1-HI2 (51.4+/-42 cm3) than in patients with PH1-PH2 (83.8+/-48 cm3) and those without HT (98.4+/-84 cm3, P=0.021). The modified Rankin scale score was significantly lower in HI1-HI2 compared with PH1-PH2 patients (1.9+/-1.1 versus 4.6+/-1.2, P<0.001) and with those without HT (1.9+/-1.1 versus 3.5+/-2.0, P=0.009.). CONCLUSIONS: Thrombolysis-related HI (HI1-HI2) represents a marker of early successful recanalization, which leads to a reduced infarct size and improved clinical outcome.

Adult↗