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1.
Neuropathol Appl Neurobiol ; 47(2): 283-296, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32896923

RESUMEN

AIMS: Recessive variants in CAPN3 gene are the cause of the commonest form of autosomal recessive limb girdle muscle dystrophy. However, two distinct in-frame deletions in CAPN3 (NM_000070.3:c.643_663del21 and c.598_621del15) and more recently, Gly445Arg and Arg572Pro substitutions have been linked to autosomal dominant (AD) forms of calpainopathy. We report 21 affected individuals from seven unrelated families presenting with an autosomal dominant form of muscular dystrophy associated with five different heterozygous missense variants in CAPN. METHODS: We have used massively parallel gene sequencing (MPS) to determine the genetic basis of a dominant form of limb girdle muscular dystrophy in affected individuals from seven unrelated families. RESULTS: The c.700G> A, [p.(Gly234Arg)], c.1327T> C [p.(Ser443Pro], c.1333G> A [p.(Gly445Arg)], c.1661A> C [p.(Tyr554Ser)] and c.1706T> C [p.(Phe569Ser)] CAPN3 variants were identified. Affected individuals presented in young adulthood with progressive proximal and axial weakness, waddling walking and scapular winging or with isolated hyperCKaemia. Muscle imaging showed fatty replacement of paraspinal muscles, variable degrees of involvement of the gluteal muscles, and the posterior compartment of the thigh and minor changes at the mid-leg level. Muscle biopsies revealed mild myopathic changes. Western blot analysis revealed a clear reduction in calpain 3 in skeletal muscle relative to controls. Protein modelling of these variants on the predicted structure of calpain 3 revealed that all variants are located in proximity to the calmodulin-binding site and are predicted to interfere with proteolytic activation. CONCLUSIONS: We expand the genotypic spectrum of CAPN3-associated muscular dystrophy due to autosomal dominant missense variants.


Asunto(s)
Calpaína/genética , Predisposición Genética a la Enfermedad/genética , Proteínas Musculares/genética , Distrofia Muscular de Cinturas/genética , Adolescente , Adulto , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Análisis de Secuencia de ADN , Adulto Joven
2.
Philos Trans A Math Phys Eng Sci ; 379(2190): 20200174, 2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33342380

RESUMEN

By direct measurements of the gas temperature, the Atacama Large Millimeter/submillimeter Array (ALMA) has yielded a new diagnostic tool to study the solar chromosphere. Here, we present an overview of the brightness-temperature fluctuations from several high-quality and high-temporal-resolution (i.e. 1 and 2 s cadence) time series of images obtained during the first 2 years of solar observations with ALMA, in Band 3 and Band 6, centred at around 3 mm (100 GHz) and 1.25 mm (239 GHz), respectively. The various datasets represent solar regions with different levels of magnetic flux. We perform fast Fourier and Lomb-Scargle transforms to measure both the spatial structuring of dominant frequencies and the average global frequency distributions of the oscillations (i.e. averaged over the entire field of view). We find that the observed frequencies significantly vary from one dataset to another, which is discussed in terms of the solar regions captured by the observations (i.e. linked to their underlying magnetic topology). While the presence of enhanced power within the frequency range 3-5 mHz is found for the most magnetically quiescent datasets, lower frequencies dominate when there is significant influence from strong underlying magnetic field concentrations (present inside and/or in the immediate vicinity of the observed field of view). We discuss here a number of reasons which could possibly contribute to the power suppression at around 5.5 mHz in the ALMA observations. However, it remains unclear how other chromospheric diagnostics (with an exception of Hα line-core intensity) are unaffected by similar effects, i.e. they show very pronounced 3-min oscillations dominating the dynamics of the chromosphere, whereas only a very small fraction of all the pixels in the 10 ALMA datasets analysed here show peak power near 5.5 mHz. This article is part of the Theo Murphy meeting issue 'High-resolution wave dynamics in the lower solar atmosphere'.

3.
Appetite ; 142: 104347, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31278956

RESUMEN

Few children in the United States meet national fruit and vegetable intake recommendations, highlighting a need for interventions. Children's food preferences act as a barrier to fruit and vegetable consumption, but prior research has demonstrated that repeated taste exposures can increase children's acceptance of these foods. Prior research in this area has typically utilized controlled procedures in which children sample small tastes of target foods over repeated occasions. The primary aim of the present pilot study was to test whether children's preferences for target fruits and vegetables increased following repeated taste exposures to them through hands-on cooking in a community setting. Seventeen 6-to-8-year-old children participated in biweekly study sessions during six weeks of a summer camp serving lower-income families. Liking of (yummy, just OK, yucky) and rank-ordered preferences for nine fruits and vegetables were measured before and after exposure sessions (pre-test and post-test). Based on pre-test assessments, four relatively less liked foods (two fruits, two vegetables) were chosen to become target foods. Children were then exposed to target foods during nine hands-on cooking sessions; liking of target foods was also measured at a midpoint assessment. At each exposure session, children assisted with preparation of a different snack using a recipe involving target foods and then ate the prepared snack together. Preferences for target foods increased from pre-test (Median = 5.8) to post-test (Median = 5.5; p < 0.05). On average, the majority of children rated the prepared snacks favorably. Results from this pilot study demonstrate the potential of applying repeated exposure techniques via hands-on cooking in a community setting.


Asunto(s)
Culinaria/métodos , Preferencias Alimentarias/psicología , Frutas , Educación en Salud/métodos , Promoción de la Salud/métodos , Verduras , Niño , Femenino , Asistencia Alimentaria , Humanos , Masculino , New York , Proyectos Piloto , Pobreza , Ingesta Diaria Recomendada , Bocadillos
4.
Microb Ecol ; 75(3): 701-719, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28975425

RESUMEN

Interactions among members of microbial consortia drive the complex dynamics in soil, gut, and biotechnology microbiomes. Proteomic analysis of defined co-cultures of well-characterized species provides valuable information about microbial interactions. We used a label-free approach to quantify the responses to co-culture of two model bacterial species relevant to soil and rhizosphere ecology, Bacillus atrophaeus and Pseudomonas putida. Experiments determined the ratio of species in co-culture that would result in the greatest number of high-confidence protein identifications for both species. The 281 and 256 proteins with significant shifts in abundance for B. atrophaeus and P. putida, respectively, indicated responses to co-culture in overall metabolism, cell motility, and response to antagonistic compounds. Proteins associated with a virulent phenotype during surface-associated growth were significantly more abundant for P. putida in co-culture. Co-culture on agar plates triggered a filamentous phenotype in P. putida and avoidance of P. putida by B. atrophaeus colonies, corroborating antagonistic interactions between these species. Additional experiments showing increased relative abundance of P. putida under conditions of iron or zinc limitation and increased relative abundance of B. atrophaeus under magnesium limitation were consistent with patterns of changes in abundance of metal-binding proteins during co-culture. These results provide details on the nature of interactions between two species with antagonistic capabilities. Significant challenges remaining for the development of proteomics as a tool in microbial ecology include accurate quantification of low-abundance peptides, especially from rare species present at low relative abundance in a consortium.


Asunto(s)
Técnicas de Cocultivo , Interacciones Microbianas/fisiología , Modelos Biológicos , Proteómica , Microbiología del Suelo , Antibacterianos/metabolismo , Antibiosis , Bacillus/crecimiento & desarrollo , Bacillus/metabolismo , Proteínas Bacterianas , Toxinas Bacterianas/metabolismo , Biopelículas , Medios de Cultivo/química , Hierro/metabolismo , Magnesio/metabolismo , Proteoma , Pseudomonas putida/crecimiento & desarrollo , Pseudomonas putida/metabolismo , Rizosfera , Metabolismo Secundario , Suelo , Factores de Virulencia/metabolismo , Zinc/metabolismo
5.
J Appl Microbiol ; 118(3): 672-84, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25494882

RESUMEN

AIMS: The aim of this study was to evaluate effects of PGPR (plant growth-promoting rhizobacteria) isolated from rainforest soil on different plants under limited nitrogen conditions. METHODS AND RESULTS: Bacterial isolates from a Peruvian rainforest soil were screened for plant growth-promoting effects on Arabidopsis (Col-0). Four selected isolates including one Bacillus subtilis, two B. atrophaeus and one B. pumilus significantly promoted growth of Zea mays L. and Solanum lycopersicum under greenhouse conditions. Moreover, the PGPRs significantly promoted growth of S. lycopersicum in both low and nitrogen-amended soil conditions. These PGPR strains were further studied to obtain insights into possible mechanisms of plant growth promotion. Volatile chemicals from those isolates promoted Arabidopsis growth, and the expression of genes related to IAA production was induced in the Arabidopsis plants treated with PGPRs. Further, selected PGPR strains triggered induced systemic resistance (ISR) against Pseudomonas syringae pv tomato DC3000 in Arabidopsis. CONCLUSIONS: PGPR strains isolated from the rainforest soil promoted the plant growth of Arabidopsis, corn and tomato. SIGNIFICANCE AND IMPACT OF THE STUDY: New PGPR that have wider adaptability to different crops, soils and environmental conditions are needed to decrease our reliance on agricultural amendments derived from fossil-based fuels. The PGPRs isolated from a nonagricultural site constitute new plant growth-promoting strains that could be developed for agricultural uses.


Asunto(s)
Bacillus/fisiología , Productos Agrícolas/crecimiento & desarrollo , Bosque Lluvioso , Microbiología del Suelo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/microbiología , Bacillus/aislamiento & purificación , Bacillus/metabolismo , Bacillus subtilis/aislamiento & purificación , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/microbiología , Datos de Secuencia Molecular , Nitrógeno/metabolismo , Pseudomonas syringae , Zea mays/crecimiento & desarrollo , Zea mays/microbiología
6.
Appl Environ Microbiol ; 76(7): 2192-202, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20139321

RESUMEN

Cellulose degradation, fermentation, sulfate reduction, and methanogenesis are microbial processes that coexist in a variety of natural and engineered anaerobic environments. Compared to the study of 16S rRNA genes, the study of the genes encoding the enzymes responsible for these phylogenetically diverse functions is advantageous because it provides direct functional information. However, no methods are available for the broad quantification of these genes from uncultured microbes characteristic of complex environments. In this study, consensus degenerate hybrid oligonucleotide primers were designed and validated to amplify both sequenced and unsequenced glycoside hydrolase genes of cellulose-degrading bacteria, hydA genes of fermentative bacteria, dsrA genes of sulfate-reducing bacteria, and mcrA genes of methanogenic archaea. Specificity was verified in silico and by cloning and sequencing of PCR products obtained from an environmental sample characterized by the target functions. The primer pairs were further adapted to quantitative PCR (Q-PCR), and the method was demonstrated on samples obtained from two sulfate-reducing bioreactors treating mine drainage, one lignocellulose based and the other ethanol fed. As expected, the Q-PCR analysis revealed that the lignocellulose-based bioreactor contained higher numbers of cellulose degraders, fermenters, and methanogens, while the ethanol-fed bioreactor was enriched in sulfate reducers. The suite of primers developed represents a significant advance over prior work, which, for the most part, has targeted only pure cultures or has suffered from low specificity. Furthermore, ensuring the suitability of the primers for Q-PCR provided broad quantitative access to genes that drive critical anaerobic catalytic processes.


Asunto(s)
Archaea/enzimología , Bacterias/enzimología , Celulosa/metabolismo , Metagenómica/métodos , Metano/metabolismo , Sulfatos/metabolismo , Archaea/genética , Archaea/metabolismo , Proteínas Arqueales/genética , Bacterias/genética , Bacterias/metabolismo , Proteínas Bacterianas/genética , Reactores Biológicos/microbiología , Cartilla de ADN/genética , ADN de Archaea/química , ADN de Archaea/genética , ADN Bacteriano/química , ADN Bacteriano/genética , Fermentación , Datos de Secuencia Molecular , Oxidación-Reducción , Sensibilidad y Especificidad , Análisis de Secuencia de ADN
7.
J Appl Microbiol ; 108(6): 2088-102, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19919618

RESUMEN

AIMS: To complement our proteome study, whole-transcriptome analyses were utilized here to identify proteins related to degrading cis-1,2-dichloroethylene (cis-DCE). METHODS AND RESULTS: Metabolically engineered Escherichia coli strains were utilized expressing an evolved toluene ortho-monooxygenase along with either (i) glutathione S-transferase and altered gamma-glutamylcysteine synthetase or (ii) a rationally engineered epoxide hydrolase. cis-DCE degradation induced 30 known stress genes and 32 uncharacterized genes. Because of the reactive cis-DCE epoxides formed, we hypothesized that some of these uncharacterized genes may be related to a variety of stresses. Using isogenic mutants, IbpB, YchH, YdeI, YeaR, YgiW, YoaG and YodD were related to hydrogen peroxide, cadmium and acid stress. Additional whole-transcriptome studies with hydrogen peroxide stress using the most hydrogen peroxide-sensitive mutants, ygiW and ychH, identified that FliS, GalS, HcaR, MglA, SufE, SufS, Tap, TnaB, YhcN and YjaA are also involved in the stress response of E. coli to hydrogen peroxide, cadmium and acid, as well as are involved in biofilm formation. CONCLUSION: Seventeen proteins are involved in the stress network for this organism, and YhcN and YchH were shown to be important for the degradation of cis-DCE. SIGNIFICANCE AND IMPACT OF THE STUDY: Six previously uncharacterized proteins (YchH, YdeI, YgiW, YhcN, YjaA and YodD) were shown to be stress proteins.


Asunto(s)
Dicloroetilenos/farmacología , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Contaminantes Ambientales/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Perfilación de la Expresión Génica , Glutamato-Cisteína Ligasa/genética , Glutamato-Cisteína Ligasa/metabolismo , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Peróxido de Hidrógeno/farmacología , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteoma/metabolismo , Estrés Fisiológico
8.
J Neurol Neurosurg Psychiatry ; 80(9): 998-1001, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19332421

RESUMEN

OBJECTIVE: Brain amyloid imaging using positron emission tomography (PET) is of increasing importance in the premortem evaluation of dementias, particularly in relation to Alzheimer disease (AD). The purpose of this study was to explore the premortem diagnostic utility of (11)C-PiB PET in sporadic Creutzfeldt-Jakob disease (CJD). METHODS: Two patients, 72 and 59 years old, underwent evaluation for rapidly progressive cognitive decline, dying after illness durations of 5 and 7 months, respectively. As part of their comprehensive assessment, (18)F-FDG PET and (11)C-PiB PET studies were performed approximately 2-4 weeks prior to death, and the brain regional distributions compared with those from cohorts of healthy controls (HC) and AD patients. RESULTS: Routine investigations, including brain MRI scans, revealed changes typical of sporadic CJD, with the diagnosis confirmed at autopsy in both patients. The (18)F-FDG PET showed global hypometabolism in one patient and thalamic and frontal hypometabolism with unexpected hypermetabolism in the dentate nuclei of the cerebellum in the other. Neither patient displayed cerebral cortical (11)C-PiB PET retention above the levels observed in HC. CONCLUSIONS: No grey-matter (11)C-PiB retention was observed in two pathologically confirmed cases of typical sporadic CJD. We speculate that low PrP plaque density and small plaque size, as well as a relatively low affinity of the radioligand, explain the absence of (11)C-PiB retention. More studies to validate this hypothesis are warranted.


Asunto(s)
Benzotiazoles , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Anciano , Compuestos de Anilina , Encéfalo/patología , Química Encefálica/fisiología , Codón/genética , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patología , Resultado Fatal , Femenino , Fluorodesoxiglucosa F18 , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Tiazoles
9.
J Ind Microbiol Biotechnol ; 36(2): 253-60, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18979124

RESUMEN

Nitroexplosives are essential for security and defense of the nation and hence their production continues. Their residues and transformed products, released in the environment are toxic to both terrestrial and aquatic life. This necessitates remediation of wastewaters containing such hazardous chemicals to reduce threat to human health and environment. Bioremediation technologies using microorganisms become the present day choice. High Melting Explosive (HMX) is one of the nitroexplosives produced by nitration of hexamine using ammonium nitrate and acetic anhydride and hence the wastewater bears high concentration of nitrate and acetate. The present investigation describes potential of a soil isolate of yeast Pichia sydowiorum MCM Y-3, for remediation of HMX wastewater in fixed film bioreactor (FFBR). The flask culture studies showed appreciable growth of the organism in HMX wastewater under shake culture condition within 5-6 days of incubation at ambient temperature (28 +/- 2 degrees C). The FFBR process operated in both batch and continuous mode, with Hydraulic Retention Time (HRT) of 1 week resulted in 50-55% removal in nitrate, 70-88% in acetate, 50-66% in COD, and 28-50% in HMX content. Continuous operation of the reactor showed better removal of nitrate as compared to that in the batch operation, while removal of acetate and COD was comparable in both the modes of operation of the reactor. Insertion of baffles in the reactor increased efficiency of the reactor. Thus, FFBR developed with baffles and operated in continuous mode will be beneficial for bioremediation of high nitrate and acetate containing wastewater using the culture of P. sydowiorum.


Asunto(s)
Azocinas/metabolismo , Biodegradación Ambiental , Reactores Biológicos/microbiología , Sustancias Explosivas/metabolismo , Nitratos/metabolismo , Pichia/metabolismo , Eliminación de Residuos Líquidos/métodos , Microbiología Industrial , Residuos Industriales , Pichia/crecimiento & desarrollo , Pichia/aislamiento & purificación , Microbiología del Suelo
10.
Biotechnol Bioeng ; 101(4): 702-13, 2008 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-18512260

RESUMEN

Five microbial inocula were evaluated in batch tests for the ability to remediate mine drainage (MD). Dairy manure (DM), anaerobic digester sludge, substrate from the Luttrell (LUTR) and Peerless Jenny King (PJK) sulfate-reducing permeable reactive zones (SR-PRZs) and material from an MD-treatment column that had been inoculated with material from a previous MD-treatment column were compared in terms of sulfate and metal removal and pH neutralization. The microbial communities were characterized at 0, 2, 4, 9, and 14 weeks using denaturing gradient gel electrophoresis and quantitative polymerase chain reaction to quantify all bacteria and the sulfate-reducing bacteria of the genus Desulfovibrio. The cultures inoculated with the LUTR, PJK, and DM materials demonstrated significantly higher rates of sulfate and metal removal, and contained all the microorganisms associated with the desired functions of SR-PRZs (i.e., polysaccharide degradation, fermentation, and sulfate reduction) as well as a relatively high proportion of Desulfovibrio spp. These results demonstrate that inoculum influences performance and also provide insights into key aspects of inoculum composition that impact performance. This is the first systematic biomolecular examination of the relationship between microbial community composition and MD remediation capabilities.


Asunto(s)
Bacterias/aislamiento & purificación , Bacterias/metabolismo , Biodiversidad , Restauración y Remediación Ambiental , Metales/metabolismo , Microbiología del Suelo , Sulfatos/metabolismo , Bacterias/genética , Metabolismo de los Hidratos de Carbono , Recuento de Colonia Microbiana/métodos , Dermatoglifia del ADN , Electroforesis en Gel Bidimensional/métodos , Estiércol/microbiología , Reacción en Cadena de la Polimerasa/métodos , Aguas del Alcantarillado/microbiología
11.
Water Res ; 41(4): 904-14, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17222885

RESUMEN

Sulfate-reducing permeable reactive zones (SR-PRZs) are a passive means of immobilizing metals and neutralizing the pH of mine drainage through microbially mediated reactions. In this bench-scale study, the influence of inoculum on the performance of columns simulating SR-PRZs was investigated using chemical and biomolecular analyses. Columns inoculated from two sources (bovine dairy manure (DM) and a previous sulfate-reducing column (SRC)) and uninoculated columns (U) were fed a simulated mine drainage and compared on the basis of pH neutralization and removal of cadmium, zinc, iron, and sulfate. Cadmium, zinc, and sulfate removal was significantly higher in SRC columns than in the DM and U columns, while there was no significant difference between the DM and U columns. Denaturing gradient gel electrophoresis (DGGE) analysis revealed differences in the microbial community composition among columns with different inocula, and indicated that the microbial community in the SRC columns was the first to reach a pseudo-steady state. In the SRC columns, a higher proportion of the DGGE band DNA sequences were related to microorganisms that carry out cellulose degradation, the rate-limiting step in SR-PRZ energy flow, than was the case in the other columns. The proportion of sulfate-reducing bacteria of the genus Desulfobacterium was monitored using real-time quantitative PCR and was observed to be consistently higher in the SRC columns. The results of this study suggest that the inoculum plays an important role in SR-PRZ performance. This is the first report providing a detailed analysis of the effect of different microbial inocula on the remediation of acid mine drainage.


Asunto(s)
Estiércol/microbiología , Metales Pesados/química , Minería , Sulfatos/química , Bacterias Reductoras del Azufre/metabolismo , Contaminantes Químicos del Agua/química , Biodegradación Ambiental , Deltaproteobacteria/metabolismo , Metales Pesados/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Sulfatos/aislamiento & purificación , Factores de Tiempo , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua/métodos
12.
J Econ Entomol ; 100(4): 1129-35, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17849861

RESUMEN

Genetically engineered corn hybrids that contain a cry gene from the bacterium Bacillus thuringiensis Berliner (Bt) are gaining popularity for controlling the corn pest Ostrinia nubilalis (Hübner). Continuous use of Bt corn, however, could select for O. nubilalis that are resistant to this corn. Monitoring for insect resistance is important, because it could help maintain the Bt technology. A possible monitoring method is to collect larval insects in commercial drying bins after harvest from Bt seed production fields. A drawback to this method is that these collections may be contaminated by insects that moved as later instars from severed non-Bt male rows into the adjacent Bt female rows. These larvae have little to no exposure to Bt toxin, resulting in possible "false positives." The objectives of this study were to first find which combination of planting and severing dates produces the least number of larvae that move from non-Bt male plants to Bt female plants and to assess O. nubilalis larval movement from severed non-Bt male rows to Bt female rows. Field studies in 2002 and 2003 were designed to simulate a hybrid seed production field. Results suggest that movement of O. nubilalis larvae from male corn is minimized when corn is planted early and male plants are severed by 2 wk post-anthesis. This reduces the likelihood of false positives by reducing the number of susceptible larvae moving between Bt and non-Bt plants. Also, larvae moved to all four female rows that were adjacent to the severed rows, but there were significantly more larvae found in the closest row compared with the other three. These results could be used to develop a monitoring program to find O. nubilalis larvae with resistance to Bt corn in field populations of O. nubilalis.


Asunto(s)
Migración Animal , Control de Insectos/métodos , Mariposas Nocturnas/fisiología , Zea mays/parasitología , Agricultura/métodos , Animales , Bacillus thuringiensis/genética , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Endotoxinas/genética , Proteínas Hemolisinas/genética , Hibridación Genética , Resistencia a los Insecticidas , Larva/fisiología , Mariposas Nocturnas/efectos de los fármacos , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/parasitología , Semillas/genética , Semillas/parasitología , Semillas/fisiología , Factores de Tiempo , Zea mays/genética , Zea mays/crecimiento & desarrollo
13.
J Natl Cancer Inst Monogr ; (14): 119-29, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8123349

RESUMEN

In 1987, the Division of Cancer Prevention and Control, National Cancer Institute (NCI), funded a randomized trial of a proactive counseling protocol to promote screening mammography among age-eligible female callers to the Cancer Information Service (CIS). This protocol included interactive counseling by CIS counselors to help callers overcome barriers to screening mammography; this counseling was an extension of usual service and was combined with a 2-week follow-up mailout to reinforce the brief (6-minute) proactive telephone-counseling protocol. The screening-mammography counseling intervention was tested in two regional CIS offices using a randomized two-group design. Callers were randomly assigned to the intervention or control group based on the week of their call to the CIS (n = 1831 eligible female callers). Self-reported adherence to NCI screening-mammography guidelines was assessed from telephone interviews conducted at 12 months' follow-up (87% response rate). Among all CIS callers enrolled in this study, self-reported adherence to screening-mammography guidelines at 12 months' follow-up was 63.5%. The most frequently cited barriers to screening mammography reported by CIS callers were inconvenience/being too busy (52%), cost (36%), lack of physician referral (34%), no symptoms (34%), and fear of radiation (29%). A significant intervention effect on adherence behavior was found but only in one of the two test sites and only among CIS callers reporting total family income of $30,000 or more (odds ratio = 1.38, P = .04). The vast majority (90%) of CIS callers (both intervention and control subjects) endorsed the concept of proactive counseling by the CIS. The implications of these findings for the CIS and future research are discussed.


Asunto(s)
Consejo , Servicios de Información , Mamografía , Oncología Médica/educación , Adulto , Anciano , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad
14.
Neurology ; 59(3): 348-56, 2002 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-12177367

RESUMEN

OBJECTIVE: To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder. METHODS: The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach. RESULTS: All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX). CONCLUSIONS: XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms.


Asunto(s)
Proteínas de Drosophila/genética , Epilepsias Mioclónicas/genética , Genes Homeobox/genética , Ligamiento Genético/genética , Discapacidades para el Aprendizaje/genética , Espasticidad Muscular/genética , Mutación Missense/genética , Cromosoma X/genética , Adulto , Anciano , Niño , Preescolar , Femenino , Tamización de Portadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Linaje
15.
Environ Health Perspect ; 105 Suppl 1: 179-95, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9114286

RESUMEN

Mixture toxicity is a topic that has become a matter of concern during the last two decades. One of the major problems with assessing the toxicity of mixtures and the associated human and environmental risk is the large number of possible mixtures, as well as the fact that the actual mixture effect for a given set of constituents might strongly depend on the actual composition of the mixture, i.e., the ratios of the constituent, as well as their nature. This paper presents a possible approach to describe and thereby better understand the pharmacokinetics and dynamics of complex mixtures by combining quantitative structure-activity relationships to predict needed parameters, lumping to reduce the complexity of the problem, and physiologically based pharmacokinetic/pharmacodynamic modeling to integrate all this information into a complete toxicological description of the mixture. It is our hope that by presenting this conceptual approach we might be able to stimulate some criticisms and discussions in the toxicology community regarding this complex and yet very important area of research.


Asunto(s)
Petróleo/toxicidad , Animales , Salud Ambiental , Humanos , Matemática , Modelos Biológicos , Exposición Profesional , Petróleo/metabolismo , Farmacocinética , Farmacología , Medición de Riesgo , Relación Estructura-Actividad , Toxicología
16.
Environ Health Perspect ; 109(12): 1207-13, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11748027

RESUMEN

We modified the two-stage Moolgavkar-Venzon-Knudson (MVK) model for use with Syrian hamster embryo (SHE) cell neoplastic progression. Five phenotypic stages are proposed in this model: Normal cells can either become senescent or mutate into immortal cells followed by anchorage-independent growth and tumorigenic stages. The growth of normal SHE cells was controlled by their division, death, and senescence rates, and all senescent cells were converted from normal cells. In this report, we tested the modeling of cell kinetics of the first two phenotypic stages against experimental data evaluating the effects of arsenic on SHE cells. We assessed cell division and death rates using flow cytometry and correlated cell division rates to the degree of confluence of cell cultures. The mean cell death rate was approximately equal to 1% of the average division rate. Arsenic did not induce immortalization or further mutations of SHE cells at concentrations of 2 microM and below, and chromium (3.6 microM) and lead (100 microM) had similar negative results. However, the growth of SHE cells was inhibited by 5.4 microM arsenic after a 2-day exposure, with cells becoming senescent after only 16 population doublings. In contrast, normal cells and cells exposed to lower arsenic concentrations grew normally for at least 30 population doublings. The biologically based model successfully predicted the growth of normal and arsenic-treated cells, as well as the senescence rates. Mechanisms responsible for inducing cellular senescence in SHE cells exposed to arsenic may help explain the apparent inability of arsenic to induce neoplasia in experimental animals.


Asunto(s)
Apoptosis/efectos de los fármacos , Arsénico/efectos adversos , División Celular/efectos de los fármacos , Desarrollo Embrionario y Fetal/efectos de los fármacos , Modelos Biológicos , Animales , Técnicas de Cultivo de Célula , Senescencia Celular , Cricetinae , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Mesocricetus , Embarazo
17.
Ann Thorac Surg ; 60(2 Suppl): S151-5, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7646148

RESUMEN

The incidence of fever of unknown origin was studied in 3 groups of patients undergoing aortic valve replacement. Fever of unknown origin was defined as a fever greater than 38.3 degrees C detected after the third postoperative day and which initiated a negative "fever work-up." Fifty patients underwent aortic valve replacement using cyropreserved allografts. Of the 49 patients who survived the operation, 13 (26%) developed fever of unknown origin. Only 1 (2%) of 51 patients, and 4 (8%) patients undergoing aortic valve replacement with a mechanical prosthesis and porcine xenograft, respectively, developed fever of unknown origin (p = 0.0034). Fever of unknown origin after allograft aortic valve replacement developed between the fourth and sixth postoperative days, with no other associated symptoms or signs. It lasted for 24 to 48 hours, and resolved without treatment. Univariate analysis revealed that fever of unknown origin occurred in younger patients (39.9 +/- 9.4 versus 50.8 +/- 11.8 years of age). The mean white blood cell count in fever of unknown origin and afebrile patients were similar (10.4 +/- 3.2 and 8.9 +/- 2.3, p = NS), both of which were significantly lower than the white blood cell count in patients with documented infection (15.0 +/- 5.2, p = 0.02; p < 0.001). No association could be demonstrated between the fever of unknown origin and gender, previous endocarditis, operative technique, cardiopulmonary bypass or cross-clamp times, ABO match, or perioperative blood transfusions. We conclude that a significant number of patients undergoing allograft aortic valve replacement develop noninfectious postoperative fever. The etiology remains unknown, but low-grade rejection cannot be excluded.


Asunto(s)
Válvula Aórtica/trasplante , Criopreservación , Fiebre de Origen Desconocido/etiología , Complicaciones Posoperatorias , Adulto , Anciano , Femenino , Humanos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Trasplante Homólogo
18.
Brain Res ; 911(2): 163-7, 2001 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-11511385

RESUMEN

A prominent side effect of Paclitaxel chemotherapy is sensorimotor peripheral neuropathy. Leukaemia inhibitory factor (LIF) supports the survival and regrowth of axotomised sensory and motor neurons and we therefore investigated if systemically administered LIF abrogated Paclitaxel-induced neuropathy. We found that whereas animals administered Paclitaxel alone exhibited a significant decrease in the percentage of large myelinated axons, this reduction was prevented by the co-administration of LIF.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Axones/efectos de los fármacos , Interacciones Farmacológicas/fisiología , Inhibidores de Crecimiento/farmacología , Interleucina-6 , Linfocinas/farmacología , Degeneración Nerviosa/tratamiento farmacológico , Paclitaxel/farmacología , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Animales , Axones/patología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Recuento de Células , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/patología , Inmunohistoquímica , Factor Inhibidor de Leucemia , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/fisiopatología , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/patología , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Ratas , Ratas Wistar , Sustancia P/metabolismo
19.
J Biotechnol ; 25(1-2): 115-44, 1992 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1368458

RESUMEN

In this article, the applications of immunoanalysis and flow cytometry for research and process monitoring in biotechnology are discussed. Brief reviews of the two analytical methods are followed by descriptions of actual applications in various areas of biotechnology. In the case of immunoanalysis, emphasis is placed on systems for on-line bioprocess monitoring, and examples are given for a thermostable pullulanase, a mouse IgG, and antithrombin III. Although flow cytometry is not currently an on-line analytical technique, its value as an off-line method is illustrated by examples of the measurement of shear stress effects, lipid content, and sterol content.


Asunto(s)
Biotecnología/métodos , Citometría de Flujo/métodos , Técnicas Inmunológicas , Animales , Rayos Láser
20.
J Dev Behav Pediatr ; 5(4): 195-200, 1984 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-6206093

RESUMEN

The increasing emphasis on screening the pediatric population for developmental delays requires that rapid and efficient screening tests be developed and evaluated. This study assessed the ability of three rapid screening procedures to predict full Denver Developmental Screening Test (DDST) results. Ninety children were randomly assigned to one of three prescreening groups. The first group was prescreened with the Prescreening Developmental Questionnaire (PDQ), administered in the "standard" fashion, i.e., mother reads and answers 10 questions about her child's development. The second group was prescreened using a modified means of administering the PDQ (PDQ-M); a health care professional read each PDQ question to the mother. The third group was prescreened with the Alpern-Boll Developmental Profile II, a relatively lengthy procedure utilizing parent report information. All of the children were then tested with the DDST. Each of the prescreening procedures was highly predictive of performance on the DDST. The Alpern-Boll profile, as anticipated, demonstrated greater validity than the PDQ and PDQ-M on six of seven indices of prescreening test validity, generated from a four-group referral matrix. The PDQ-M was more similar to the Alpern-Boll on four indices, while the PDQ was more similar on three. It was judged that the two PDQ procedures were equivalent in their validity characteristics. The PDQ-M appears to be an acceptable means of rapidly screening preschool children for developmental delays.


Asunto(s)
Actitud , Desarrollo Infantil , Discapacidades del Desarrollo/diagnóstico , Padres/psicología , Pruebas Psicológicas , Preescolar , Femenino , Humanos , Lactante , Masculino , Psicometría , Derivación y Consulta
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