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INTRODUCTION AND OBJECTIVES: We previously published the toxicity and initial results of a prospective cohort of patients treated with 2 fractions HDR-BRT administered in a single day. In the present analysis we report the long-term cancer control results of our prospective trial and investigate the relationship between PSA nadir and biochemical control. MATERIAL AND METHODS: A total of 120 patients were treated with HDR Brachytherapy monotherapy administered in two fractions in a single day. Between November 2010 and February 2016, 84 patients with low-risk and 36 patients with intermediate-risk prostate cancer in accordance with the NCCN practice guidelines. RESULTS: Median age was 66 years (range 45-84) and median PSA was 7.5 ng/ml (range 0.01-16 ng/ml). Overall, 84.2% had Gleason score 6 and 15.8% Gleason 7. Thirty-one percent of patients received ADT.After a median follow-up of the cohort was 123 months. Actuarial rates of no biochemical evidence of disease (bNED), overall survival, local control and metastasis-free survival for all patients were 93.3%, 86.7%, 95.2% and 96.1%, respectively.The median time to achieve PSA nadir was 80.5 months. Patients who attained a PSA Nadir ≤ 0.20 ng/mL exhibited a 10-year bNED survival rate of 96.9%, whereas thosewho failed to reach this PSA level had a survival rate of only 40%. CONCLUSIONS: In patients with favorable localized prostate cancer, 2 fractions HDR-BT monotherapy is a highly curative radiation technique that attains PSA nadir levels < 0.2 ng/mL in 95% of cases.
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Braquiterapia , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antígeno Prostático Específico/análise , Braquiterapia/métodos , Estudos Prospectivos , Dosagem Radioterapêutica , Neoplasias da Próstata/radioterapia , SeguimentosRESUMO
The counterintuitive fact that wave chaos appears in the bending spectrum of free rectangular thin plates is presented. After extensive numerical simulations, varying the ratio between the length of its sides, it is shown that (i) frequency levels belonging to different symmetry classes cross each other and (ii) for levels within the same symmetry sector, only avoided crossings appear. The consequence of anticrossings is studied by calculating the distribution of the ratio of consecutive level spacings for each symmetry class. The resulting ratio distributions disagree with the expected Poissonian result. They are then compared with some well-known transition distributions between Poisson and the Gaussian orthogonal random matrix ensemble. It is found that the distribution of the ratio of consecutive level spacings agrees with the prediction of the Rosenzweig-Porter model. Also, the normal-mode vibration amplitudes are found experimentally on aluminum plates, before and after an avoided crossing for symmetrical-symmetrical, symmetrical-antisymmetrical, and antisymmetrical-symmetrical classes. The measured modes show an excellent agreement with our numerical predictions. The expected Poissonian distribution is recovered for the simply supported rectangular plate.
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BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain. MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments. RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (Nâ¯=â¯315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy. CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Mesotelioma/diagnóstico , Mesotelioma/epidemiologia , Mesotelioma/terapia , Neoplasias Pleurais/epidemiologia , Neoplasias Pleurais/terapia , Espanha/epidemiologiaRESUMO
Solid state physics deals with systems composed of atoms with strongly bound electrons. The tunneling probability of each electron is determined by interactions that typically extend to neighboring sites, as their corresponding wave amplitudes decay rapidly away from an isolated atomic core. This kind of description is essential in condensed-matter physics, and it rules the electronic transport properties of metals, insulators and many other solid-state systems. The corresponding phenomenology is well captured by tight-binding models, where the electronic band structure emerges from atomic orbitals of isolated atoms plus their coupling to neighboring sites in a crystal. In this work, a mechanical system that emulates dynamically a quantum tightly bound electron is built. This is done by connecting mechanical resonators via locally periodic aluminum bars acting as couplers. When the frequency of a particular resonator lies within the frequency gap of a coupler, the vibrational wave amplitude imitates a bound electron orbital. The localization of the wave at the resonator site and its exponential decay along the coupler are experimentally verified. The quantum dynamical tight-binding model and frequency measurements in mechanical structures show an excellent agreement. Some applications in atomic and condensed matter physics are suggested.
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Coherent transport phenomena are difficult to observe due to several sources of decoherence. For instance, in the electronic transport through quantum devices the thermal smearing and dephasing, the latter induced by inelastic scattering by phonons or impurities, destroy phase coherence. In other wave systems, the temperature and dephasing may not destroy the coherence and can then be used to observe the underlying wave behaviour of the coherent phenomena. Here, we observe coherent transmission of mechanical waves through a two-dimensional elastic Sinai billiard with two waveguides. The flexural-wave transmission, performed by non-contact means, shows the quantization when a new mode becomes open. These measurements agree with the theoretical predictions of the simplest model highlighting the universal character of the transmission fluctuations.
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BACKGROUND: Historically the district of Ciutat Vella in Barcelona has a high incidence of tuberculosis (TB) and, more recently, it is home to a considerable proportion of immigrants. OBJECTIVES: To determine the prevalence of tuberculous infection (TI) in a pediatric population from this district and evaluate the impact of immigration. METHODS: Children and adolescents aged < 16 years old were screened using the tuberculin skin test (TST) mainly in visits of the healthy child program. Proportions were compared using the x2 test and adjusted odds ratios were estimated through a logistic regression model. RESULTS: Six hundred ninety-nine children were studied. The overall prevalence of positive TST was 3.4 % (95 % CI: 2.2 %-5.1 %). Prevalence increased with age (P 5 0.009) from 1.9 % in children aged 1-5 years old to 6.4 % in children and adolescents aged 10-15 years. A total of 88.3 % of the immigrants had been vaccinated with BCG compared with 2.5 % of autochthonous children and adolescents (P < 0.001). The prevalence ratio between immigrants and autochthonous children was 2.1 (P 5 0.07). Three cases of TB disease were detected among children, but no index case was found in children with TI. CONCLUSIONS: The high TI prevalence found suggest that living in the district is a risk factor, which justifies routine TST screening of all the children living there. The present criteria for the interpretation of TST in immigrants vaccinated with BCG residing in areas of high incidence are dubious.
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Emigração e Imigração/estatística & dados numéricos , Tuberculose/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Espanha/epidemiologiaRESUMO
Antecedentes: Históricamente, el distrito Ciutat Vella de Barcelona presenta una elevada incidencia de tuberculosis y, más recientemente, alberga una proporción considerable de inmigrantes. Objetivos: Determinar la prevalencia de infección tuberculosa en una población pediátrica de dicho distrito, considerando el impacto de la inmigración. Métodos: Cribado de los niños menores de 16 años mediante la realización de la prueba de la tuberculina, mayoritariamente en las visitas del programa de atención al niño sano. Comparación de proporciones mediante la prueba estadística de la X2 y estimación odds ratio ajustadas mediante modelo de regresión logística. Resultados: Se estudiaron 699 niños. La prevalencia observada de pruebas de la tuberculina positivas fue 3,4 por ciento (intervalo de confianza [IC] 95 por ciento: 2,2-5,1), ésta aumentaba con la edad (p=0,009), desde 1,9 por ciento en niños de 1-5 hasta 6,4 por ciento en los de 10-15 años. Un 88,3 por ciento de los inmigrantes estaba vacunado con bacilo de Calmette-Guérin (BCG) frente al 2,5 por ciento de los autóctonos (p < 0,001). La razón de prevalencias entre los hijos de inmigrantes e inmigrantes y los niños autóctonos fue de 2,1 (p=0,07). Se detectaron 3 casos de tuberculosis en niños; no se encontró el foco en ningún caso entre los niños con infección tuberculosa. Conclusiones: La elevada prevalencia de infección tuberculosa observada sugiere que vivir en el distrito es un factor de riesgo, lo cual justifica realizar pruebas de tuberculina sistemáticas a los niños que residen allí. Los criterios actuales para valorar la prueba de la tuberculina en niños inmigrantes vacunados con BCG residentes en zonas de alta incidencia de tuberculosis, son dudosos (AU)
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Humanos , Masculino , Lactente , Pré-Escolar , Criança , Adolescente , Feminino , Emigração e Imigração , Espanha , Incidência , TuberculoseRESUMO
Terpenoids or isoprenoids constitute a vast family of organic compounds that includes sterols and carotenoids. The terpenoids in many organisms share early steps in their biosynthesis, including the synthesis of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) and its conversion to mevalonate. We have cloned and characterised the genes hmgS for HMG-CoA synthase and hmgR for HMG-CoA reductase from the Zygomycete Phycomyces blakesleeanus. Single copies of these genes are present in the Phycomyces genome. The predicted product of hmgS is largely hydrophilic and that of hmgR has eight putative transmembrane segments and a large hydrophilic domain. The hydrophilic domain suffices for catalytic activity, as shown by expressing it in Escherichia coli. Several features in the promoter of hmgS and in HMG-CoA reductase resemble motifs known to be involved in sterol-mediated regulation and sterol sensing. Carotene-overproducing mutants contain more hmgS mRNA than the wild type, possibly in response to an increased demand for HMG-CoA.
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Genes Fúngicos , Ácido Mevalônico/metabolismo , Phycomyces/genética , Phycomyces/metabolismo , Sequência de Aminoácidos , Sequência de Bases , DNA Fúngico/genética , Escherichia coli/genética , Genoma Fúngico , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Sintase/genética , Dados de Sequência Molecular , Mutação , Filogenia , Regiões Promotoras Genéticas , RNA Fúngico/genética , RNA Fúngico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/genética , Homologia de Sequência de AminoácidosRESUMO
Phycomyces has been in the laboratories for about 140 years, sometimes following trends and fashions, but often anticipating them. Researchers have been attracted by the sensitive and precise responses of Phycomyces to light and other stimuli, coupled with easy manipulations and good adaptation to laboratory life. It is a simple prototype of the many organisms that use light as a source of information but not as a significant source of energy. Growth, development, genetics, and carotene production have been other subjects of pioneering research. Phycomyces was the second organism, after us, known to require a vitamin. It was one of the first organisms in the research on spontaneous mutants and the second, after Drosophila, in which mutations were induced artificially. It was used to coin the concept and the name of heterokaryosis. Phycomyces heterokaryons offer unique experimental possibilities, for instance in the study of gene function in vivo and the causes of cell death. An overall impression of parsimony and combinatorial gene usage arises from the genetic analysis of the complex functions of this fungus. The main subjects of recent attention have been the various reactions to light, gravitropism, and some aspects of metabolism, particularly the production of carotene. Interest in Phycomyces is slacking because of the repeated failures at transforming it stably with exogenous DNA.
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Luz , Phycomyces/fisiologia , Carotenoides/metabolismo , Genes Fúngicos , Mutação , Fototropismo , Phycomyces/genética , Phycomyces/metabolismo , Visão Ocular/genéticaRESUMO
The biodegradation of phenanthrene by the biosurfactant-producing strain Pseudomonas aeruginosa 19SJ was investigated in experiments with the compound present either as crystals or dissolved in non-aqueous phase liquids (NAPLs). Growth on solid phenanthrene exhibited an initial phase not limited by dissolution rate and a subsequent, carbon-limited phase caused by exhaustion of the carbon source. Rhamnolipid biosurfactants were produced from solid phenanthrene and appeared in solution and particulate material (cells and phenanthrene crystals). During the carbon-limited phase, the concentration of rhamnolipids detected in culture exceeded the critical micelle concentration (CMC) determined with purified rhamnolipids. The biosurfactants caused a significant increase in dissolution rate and pseudosolubility of phenanthrene, but only at concentrations above the CMC. Externally added rhamnolipids at a concentration higher than the CMC increased the biodegradation rate of solid phenanthrene. Mineralization curves of low concentrations of phenanthrene initially dissolved in two NAPLs [2,2,4,4,6,8,8-heptamethylnonane and di(2-ethylhexyl)phthalate] were S-shaped, although no growth was observed in the population of suspended bacteria. Biosurfactants were not detected in solution under these conditions. The observed mineralization was attributed not only to suspended bacteria, but also to bacterial populations growing at the NAPL-water interface, mineralizing the compound at higher rates than predicted by abiotic partitioning. We suggest that rhamnolipid production and attachment increased the bioavailability of phenanthrene, so promoting biodegradation activity.
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Fenantrenos/metabolismo , Pseudomonas aeruginosa/metabolismo , Biodegradação Ambiental , Biomassa , Carbono/análise , Glicolipídeos/biossíntese , Glicolipídeos/farmacologia , Cinética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Ramnose/biossíntese , Ramnose/farmacologia , Tensoativos/metabolismoRESUMO
Sexual interaction between strains of opposite sex in many fungi of the order Mucorales modifies hyphal morphology and increases the carotene content. The progeny of crosses of Phycomyces blakesleeanus usually include a small proportion of anomalous segregants that show these signs of sexual stimulation without a partner. We have analyzed the genetic constitution of such segregants from crosses that involved a carF mutation for overaccumulation of beta-carotene and other markers. The new strains were diploids or partial diploids heterozygous for the sex markers. Diploidy was unknown in this fungus and in the Zygomycetes. Random chromosome losses during the vegetative growth of the diploid led to heterokaryosis in the coenocytic mycelia and eventually to sectors of various tints and mating behavior. The changes in the nuclear composition of the mycelia could be followed by selecting for individual nuclei. The results impose a reinterpretation of the sexual cycle of Phycomyces. Some of the intersexual strains that carried the carF mutation contained 25 mg beta-carotene per gram of dry mass and were sufficiently stable for practical use in carotene production.
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Diploide , Phycomyces/genética , Phycomyces/fisiologia , Cruzamentos Genéticos , Relação Dose-Resposta a Droga , Ácidos Graxos Insaturados/farmacologia , Genótipo , Heterozigoto , Mutação , Reprodução , beta Caroteno/biossíntese , beta Caroteno/genéticaRESUMO
Feeding experiments with ent-kaurenoic acid (4), 15 alpha-hydroxy-ent-kaurenoic acid (5), 15 beta-hydroxy-ent-kaurenoic acid (6), and mixtures of 4 plus 5 and 4 plus 6 were conducted using the SG138 mutant of Gibberella fujikuroi, to gain information about the phenotype of this unique strain. The biotransformation of 5 gave 7 beta,15 alpha-dihydroxykaurenolide (9) and 7 beta,15 alpha-dihydroxy-ent-kaurenoic acid (13). The incubation of 6 produced 7 beta,15 beta-dihydroxy-ent-kaurenoic acid (7) and 7 beta,15 beta-dihydroxykaurenolide (10). No 15-hydroxylated gibberellins were detected in any of these experiments. The results indicated that a hydroxy group at C-15 does not inhibit 7 beta-hydroxylase activity but in the SG138 strain obstructs the enzymatic ring-B contraction of ent-kaurenoids to gibberellins. Exogenous 4 stimulated both the excretion of ent-kaurene and the fungal metabolism of 5 and 6.
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Diterpenos/metabolismo , Gibberella/metabolismo , Biotransformação , Gibberella/genética , Hidroxilação , Modelos Químicos , MutaçãoRESUMO
El estrés y los estilos de afrontamiento son un tema central en la actual psicología. Las aportaciones de Lazarus y Folkman en este ámbito es de referencia obligada. Desde un punto de vista evaluativo este grupo de trabajo desarrolló con enorme aceptación el Ways of Coping Questionaire (Folkman y Lazaros, 1980 y 1986). Estructuralmente los autores defienden una composición octofactorial de la prueba, reducible a un factor de afrontamiento centrado en el problema y otro de afrontamiento centrado en la emoción. Sin embargo su validez de constructo no está bien definida. Ello se debe a la escasa replicación que esta estructura ha obtenido: los trabajos con metodología exploratoria o confirmatoria llevadas a cabo no apoyan la solución octofactorial de la escala. Recurrimos al análisis factorial restrictivo de 222 sujetos. A diferencia de trabajos previos, se contrasta una serie de modelos anidados diseñados para responder a la cuestión de si los factores de primer y segundo son discriminables y justificables. Nuestros resultados no apoyan la viabilidad de la estructura factorial sometida a consideración (AU)
Stress and coping styles are a central issue in contemporary psychology. Lazarus & Folkman contributions to this area are a crucial point. From an assessment point of view these authors developed the "Ways of Coping Questionnaire" (Folkman & Lazarus, 1980, 1986). In 'um, these authors defend an octofactorial solution of this test. This solution would be reductible to a problem-focused coping factor and an emotion. focused coping factor. However, its construct validity is not defined at al!. This is due to the scaraty of replications this structure has obtained. Studies carried out with exploratory or confirmatory methodology, do not support the octofactorial soIution of the scale. We developed a restrictive factorial analysis from 222 subjects. Unlike previous works, in this study a series of nested models to answer the question of weather first and second order factors are or not justified. This study doesn't find the proposed factorial structure (AU)
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Humanos , Adaptação Psicológica , Estresse Psicológico/psicologia , Psicometria/instrumentação , Análise Fatorial , Reprodutibilidade dos Testes , Reprodutibilidade dos TestesRESUMO
Previous complementation and mapping of mutations that change the usual yellow color of the Zygomycete Phycomyces blakesleeanus to white or red led to the definition of two structural genes for carotene biosynthesis. We have cloned one of these genes, carRA, by taking advantage of its close linkage to the other, carB, responsible for phytoene dehydrogenase. The sequences of the wild type and six mutants have been established, compared with sequences in other organisms, and correlated with the mutant phenotypes. The carRA and carB coding sequences are separated by 1,381 untranslated nucleotides and are divergently transcribed. Gene carRA contains separate domains for two enzymes, lycopene cyclase and phytoene synthase, and regulates the overall activity of the pathway and its response to physical and chemical stimuli from the environment. The lycopene cyclase domain of carRA derived from a duplication of a gene from a common ancestor of fungi and Brevibacterium linens; the phytoene synthase domain is similar to the phytoene and squalene synthases of many organisms; but the regulatory functions appear to be specific to Phycomyces.
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Alquil e Aril Transferases/genética , Carotenoides/biossíntese , Genes Fúngicos , Liases Intramoleculares/genética , Sequência de Aminoácidos , Sequência de Bases , DNA Fúngico , Geranil-Geranildifosfato Geranil-Geraniltransferase , Dados de Sequência Molecular , Phycomyces/enzimologia , Phycomyces/genética , Phycomyces/metabolismo , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
PURPOSE: A subset of newborns with myelodysplasia have normal bladder function on urodynamic assessment. We analyzed long-term followup in this population to determine the necessity for subsequent urological surveillance. MATERIALS AND METHODS: We retrospectively analyzed the records of 25 of 204 newborns (12%) with myelodysplasia in whom neurourological evaluation was normal after surgical repair of the spinal defect. Initial assessment included complete urodynamic study, renal ultrasound, urinalysis and urine culture. These patients were reevaluated every 3 months until age 3 years, semiannually until age 6 years and yearly thereafter. The longest followup was 18.6 years. RESULTS: Of the 25 newborns 22 had myelomeningocele and 3 had meningocele. During a mean followup of 9.1 years urodynamics subsequently showed neurourological deterioration in 8 children (32%). No changes in urodynamics were observed in any patient older than 6 years. All children with neurourological deterioration underwent magnetic resonance imaging, which confirmed a tethered spinal cord that was then surgically corrected. After the untethering procedure 2 patients (25%) regained normal voiding function, whereas in 6 (75%) mild or moderate neurogenic bladder dysfunction persisted. CONCLUSIONS: Newborns with myelodysplasia and initially normal urodynamic studies are at risk for neurological deterioration secondary to spinal cord tethering, especially during the first 6 years of life. Close followup of these children is important for the early diagnosis and timely surgical correction of tethered spinal cord, and for the prevention of progressive urinary tract deterioration.
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Defeitos do Tubo Neural/fisiopatologia , Urodinâmica , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
Sterols and gibberellins are the main terpenoids in the Ascomycete Fusarium fujikuroi. Their respective precursors squalene and ent-kaur-16-ene (henceforth called kaurene) were the main terpenoids synthesised from radioactive mevalonate by extracts of F. fujikuroi in vitro. Kaurene predominated when the extracts were obtained from mycelia engaged in gibberellin production. Squalene predominated in all other cases, and particularly when the extracts were obtained from mutants with various defects in gibberellin synthesis or nitrogen-fed wild-type cultures. New protein synthesis was required to maintain the production of gibberellins in vivo and of kaurene in vitro, but not to maintain the capacity to produce squalene in vitro. Addition of a nitrogen source to cultures engaged in gibberellin production caused a large, transient increase in the mycelial concentration of L-glutamine and abolished the accumulation of gibberellins immediately and the capacity to produce kaurene later.
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Diterpenos do Tipo Caurano , Fusarium/metabolismo , Esqualeno/metabolismo , Sistema Livre de Células , Diterpenos , Fusarium/citologiaRESUMO
The ascomycete Fusarium fujikuroi could be transformed stably to hygromycin resistance only when the transforming plasmid contained a fragment of DNA from the fungus. The transformation frequencies were roughly independent of the sequence of the particular fungal DNA fragment used, of its size (1.8 or 6 kb), and of whether this DNA was present only once in the fungal genome or about forty times (the genes for ribosomal RNA). The plasmid was integrated into the fungal genome by homologous recombination in the eighteen transformants tested; ectopic integration was never observed. The carB gene of F. fujikuroi was cloned and shown to complement unpigmented mutants deficient in phytoene dehydrogenase. A mutant carB allele was prepared in vitro and used to transform wild-type protoplasts; the transformants contained a genomic duplication and were heterozygous for carB; the mutant allele replaced the original wild-type allele when this was spontaneously lost in the transformants. This loss was due to gene conversion in some cases and to recombination between repeated sequences in others.
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Fusarium/genética , Transformação Genética , Alelos , Sequência de Bases , Clonagem Molecular , Primers do DNA/genética , DNA Fúngico/genética , Conversão Gênica , Plasmídeos/genética , Recombinação GenéticaRESUMO
Chromosome 18q is lost a high proportion of colorectal and pancreatic cancers. Three candidate tumor suppressor genes, DCC, Smad4 and Smad2 have been identified in this chromosome region. DCC and Smad4 aberrations have been previously identified in pancreatic and colorectal tumors. The aim of this study was to compare the presence of concurrent genetic aberrations in DCC and neighboring Smad4 and Smad2 genes during colorectal and pancreatic distal dissemination. We have used a panel of orthotopically implanted colorectal and pancreatic xenografts and corresponding metastases. We have shown that while LOH at DCC locus occurred at a similar frequency in both tumors, diminished DCC protein expression was exclusively present in colorectal tumors harboring intragenic DCC LOH. In contrast, in pancreatic xenografts loss of DCC protein and mRNA expression was restricted to metastases. Smad4 gene aberrations were detected at a similar frequency in both tumors and were selected for during distal dissemination. Acquisition of alterations in both genes occurred independently. Our results suggest that both DCC and Smad4 contribute to pancreatic and colorectal distal dissemination. However, the role of DCC may differ between both tumor types.
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Adenocarcinoma/genética , Cromossomos Humanos Par 18/genética , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Genes DCC , Perda de Heterozigosidade , Metástase Neoplásica/genética , Proteínas de Neoplasias/genética , Oncogenes , Neoplasias Pancreáticas/genética , Transativadores/genética , Adenocarcinoma/patologia , Adulto , Idoso , Animais , Ascite/genética , Ascite/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/fisiologia , Progressão da Doença , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Proteínas de Neoplasias/fisiologia , Transplante de Neoplasias , Células Neoplásicas Circulantes , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Proteína Smad2 , Proteína Smad4 , Transativadores/fisiologia , Transplante HeterólogoRESUMO
Sterols, carotenoids and gibberellins are synthesized after the reduction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate in different subcellular compartments of the fungus Gibberella fujikuroi. Lovastatin inhibits growth in many organisms, presumably because of the inhibition of the synthesis of essential terpenoids. However, in G. fujikuroi growth of the mycelia and sterol and carotenoid content were not affected by the presence of lovastatin. Nevertheless, lovastatin did inhibit the accumulation of gibberellins in the culture medium; this inhibition, however, was counteracted by the addition of mevalonate to the medium. The conversion of HMG-CoA to mevalonate in cell-free extracts was inhibited by 10 nM lovastatin. Since G. fujikuroi apparently possesses a single gene for HMG-CoA reductase, as shown by Southern hybridization and PCR amplification, it was concluded that the biosynthesis of sterols, carotenoids and gibberellins shares a single HMG-CoA reductase, but the respective subcellular compartments are differentially accessible to lovastatin.
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Carotenoides/biossíntese , Gibberella/efeitos dos fármacos , Giberelinas/antagonistas & inibidores , Giberelinas/biossíntese , Lovastatina/farmacologia , Esteróis/biossíntese , Acil Coenzima A/metabolismo , Sequência de Aminoácidos , Southern Blotting , DNA Fúngico , Proteínas Fúngicas , Gibberella/crescimento & desenvolvimento , Gibberella/metabolismo , Ácido Mevalônico/farmacologia , Dados de Sequência Molecular , Mapeamento Físico do Cromossomo , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Fatores de TempoRESUMO
Hepatitis B and C markers were tested in 980 pregnant women, in the infants born to infected mothers, and in a random sample of 42 and 50, respectively, children born to uninfected mothers in Tanzania. Sixty-two women (6.3%) were positive for HBsAg and 15 (24%) were HBeAg-seropositive. Anti-HCV was detected in 49 women (5%), 15 (31%) of whom had detectable viremia. HCV RNA serum levels were low and only genotype 4 was identified. Sixty-six women (6.7%) were positive for anti-HIV, six of whom were coinfected with HBV and one with HCV. Anti-HEV was negative in the 180 women tested. At 8 months of age, HBsAg was detected in 8% and 2% of children born to HBV-infected and noninfected mothers, respectively (P = 0.2). Corresponding figures at 18 months of age were 31% and 21% (P = 0.3). When tested at 2 months of age, HCV RNA was not detected in any of the 43 children born to anti-HCV-positive mothers nor in any of 50 children born to anti-HCV-negative mothers. At 18 months, only one child, born to an anti-HCV-positive mother, had detectable HCV RNA. None of the infants born to women with HIV coinfection were infected with hepatitis viruses. This study suggests that exposure to HEV does not occur in southern Tanzania. The prevalence of current HBV infection in pregnant women from rural Tanzania is lower than in other sub-Saharan areas. In early childhood, HBV infection appears to occur by horizontal rather than maternofilial mechanisms of transmission. The prevalence of HCV infection is similar to that in other African countries. The results of this study show for the first time in Africa that mother-to-infant transmission does not play a significant role in the acquisition of HCV infection.