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1.
Biometrika ; 105(2): 431-446, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29880978

RESUMO

There has been substantial recent interest in record linkage, where one attempts to group the records pertaining to the same entities from one or more large databases that lack unique identifiers. This can be viewed as a type of microclustering, with few observations per cluster and a very large number of clusters. We show that the problem is fundamentally hard from a theoretical perspective and, even in idealized cases, accurate entity resolution is effectively impossible unless the number of entities is small relative to the number of records and/or the separation between records from different entities is extremely large. These results suggest conservatism in interpretation of the results of record linkage, support collection of additional data to more accurately disambiguate the entities, and motivate a focus on coarser inference. For example, results from a simulation study suggest that sometimes one may obtain accurate results for population size estimation even when fine-scale entity resolution is inaccurate.

2.
Traffic Inj Prev ; 16(4): 374-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25022310

RESUMO

OBJECTIVE: This study applies a simulation technique to evaluate the hypothesis that red light cameras (RLCs) exert important effects on accident risks. Conflict occurrences are generated by simulation and compared at intersections with and without RLCs to assess the impact of RLCs on several conflict types under various traffic conditions. METHOD: Conflict occurrences are generated through simulating vehicular interactions based on an improved cellular automata (CA) model. The CA model is calibrated and validated against field observations at approaches with and without RLCs. Simulation experiments are conducted for RLC and non-RLC intersections with different geometric layouts and traffic demands to generate conflict occurrences that are analyzed to evaluate the hypothesis that RLCs exert important effects on road safety. RESULTS: The comparison of simulated conflict occurrences show favorable safety impacts of RLCs on crossing conflicts and unfavorable impacts for rear-end conflicts during red/amber phases. Corroborative results are found from broad analysis of accident occurrence. CONCLUSIONS: RLCs are found to have a mixed effect on accident risk at signalized intersections: crossing collisions are reduced, whereas rear-end collisions may increase. The specially developed CA model is found to be a feasible safety assessment tool.


Assuntos
Acidentes de Trânsito/prevenção & controle , Condução de Veículo/legislação & jurisprudência , Aplicação da Lei/métodos , Modelos Teóricos , Fotografação , Segurança , Calibragem , Simulação por Computador , Planejamento Ambiental , Estudos de Viabilidade , Humanos , Reprodutibilidade dos Testes , Medição de Risco
3.
J Anim Sci ; 92(4): 1306-14, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24496842

RESUMO

While feeding food-producing animals with microalgae was investigated several decades ago, this research has been reactivated by the recent exploration of microalgae as the third generation of feedstocks for biofuel production. Because the resultant defatted biomass contains high levels of protein and other nutrients, it may replace a portion of corn and soybean meal in animal diets. Our laboratory has acquired 4 types of full-fat and defatted microalgal biomass from biofuel production research (Cellana, Kailua-Kona, HI) that contain 13.9 to 38.2% crude protein and 1.5 to 9.3% crude fat. This review summarizes the safety and efficacy of supplementing 2 types of the biomass at 7.5 to 15% in the diets of weanling pigs, broiler chicks, and laying hens. Based on their responses of growth performance, egg production and quality, plasma and tissue biochemical indicators, and/or fecal chemical composition, all 3 types of animals were able to tolerate the microalgal biomass incorporation into their diets at 7.5% (on as-fed basis). Holistic analysis is also provided to explore the global potential of using the defatted microalgal biomass as a new feed ingredient in offsetting the biofuel production cost, reducing the dependence on staple crops such as corn and soybeans, decreasing greenhouse gas production of animal agriculture, and developing health value-added animal products.


Assuntos
Ração Animal/análise , Galinhas/fisiologia , Dieta/veterinária , Gorduras/química , Microalgas/química , Suínos/fisiologia , Animais
4.
Prostate Cancer Prostatic Dis ; 13(3): 248-51, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20514082

RESUMO

The objective of this study was to preoperatively predict non-organ-confined disease in patients considering radical prostatectomy. To account for the stage migration seen in prostate cancer, we included only those patients who underwent prostatectomy after the year 2000. Information on a cohort of 1895 patients who underwent radical prostatectomy from 2000 to 2008 was retrieved from the Duke Prostate Center database. Race (African American, non-African American), body mass index, age at surgery, PSA, biopsy Gleason sum (<7, 7 and >7) and clinical tumor stage (cT1, cT2/3) were analyzed by univariate analysis followed by logistic regression analysis. The Duke Interactive Clinical Equation for staging (DICE-S score) was calculated from the logistic regression model. The model was then internally validated using a bootstrapping technique. Biopsy Gleason sums 7 and >7 were more likely to have non-organ-confined disease compared with <7 (OR=2.97, Gleason sum=7; OR=3.25, Gleason sum>7). Clinical tumor stage, cT2/3, predicted non-organ-confined disease (OR=1.58). Older age was associated with non-organ-confined disease (OR=1.02), as was greater PSA (OR=1.12). DICE-S equation x=ln (p/1-p)=-3.627+0.019 (age)+0.109 (PSA)+1.087 (bGleason=7)+1.180 (bGleason >7)+0.459 (clinical T stage >T1), where p=(e(x))/(1+e(x)). A concordance index (prediction accuracy) of 0.73 was reached on internal validation. Using the DICE-S score, age, PSA, biopsy Gleason sum and clinical tumor stage, we can predict non-organ-confined disease in radical prostatectomy at an acceptable accuracy. Preoperative information on disease stage may aid in treatment decisions and surgical approach.


Assuntos
Prostatectomia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Antígeno Prostático Específico/sangue , Taxa de Sobrevida
5.
Tob Control ; 18(5): 377-86, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19556615

RESUMO

BACKGROUND: Tobacco tax increases reduce tobacco use, can provide funds for tobacco prevention and enjoy broad public support. Because of tobacco industry influence in legislatures, US public health advocates have shifted the venue for tobacco tax policymaking to direct popular vote 22 times since 1988. METHODS: We combined case studies of individual state campaigns with tobacco industry documents to identify strategies related to outcome. RESULTS: The tobacco industry developed a voter segmentation model to determine which tobacco tax increases it could defeat. Two industry arguments arising from this model often were raised in losing campaigns-the tax increase did not dedicate enough to tobacco control and hospitals and health maintenance organisations would profit. The industry effectively influenced early voters. Success was associated with building a strong base of public support before the campaign, dedicating sufficient funds to tobacco control, avoiding proposals largely devoted to financing hospitals and other medical service providers, effectively engaging grassroots and framing the campaign with clear justifications for cigarette tax increases. CONCLUSIONS: Tobacco tax ballot measures commonly allocated substantial funds to medical services; tobacco companies are becoming more successful in making this use of funds an issue. Proponents' campaigns should be timed to account for the trend to voting well before election day. Ballot measures to increase tobacco taxes with a substantial fraction of the money devoted to tobacco control activities will probably fare better than ones that give priority to funding medical services.


Assuntos
Opinião Pública , Fumar/economia , Impostos , Indústria do Tabaco/economia , Humanos , Formulação de Políticas , Política , Saúde Pública/legislação & jurisprudência , Fumar/legislação & jurisprudência , Abandono do Hábito de Fumar/economia , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Indústria do Tabaco/legislação & jurisprudência , Estados Unidos
6.
Tob Control ; 17(5): 313-23, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18818225

RESUMO

OBJECTIVE: Smoking in movies is associated with adolescent and young adult smoking initiation. Public health efforts to eliminate smoking from films accessible to youth have been countered by defenders of the status quo, who associate tobacco imagery in "classic" movies with artistry and nostalgia. The present work explores the mutually beneficial commercial collaborations between the tobacco companies and major motion picture studios from the late 1920s through the 1940s. METHODS: Cigarette endorsement contracts with Hollywood stars and movie studios were obtained from internal tobacco industry documents at the University of California, San Francisco (UCSF) Legacy Tobacco Documents Library and the Jackler advertising collection at Stanford. RESULTS: Cigarette advertising campaigns that included Hollywood endorsements appeared from 1927 to 1951, with major activity in 1931-2 and 1937-8 for American Tobacco Company's Lucky Strike, and in the late 1940s for Liggett & Myers' Chesterfield. Endorsement contracts and communication between American Tobacco and movie stars and studios explicitly reveal the cross-promotional value of the campaigns. American Tobacco paid movie stars who endorsed Lucky Strike cigarettes US$218,750 in 1937-8 (equivalent to US$3.2 million in 2008) for their testimonials. CONCLUSIONS: Hollywood endorsements in cigarette advertising afforded motion picture studios nationwide publicity supported by the tobacco industry's multimillion US dollar advertising budgets. Cross-promotion was the incentive that led to a synergistic relationship between the US tobacco and motion picture industries, whose artefacts, including "classic" films with smoking and glamorous publicity images with cigarettes, continue to perpetuate public tolerance of onscreen smoking. Market-based disincentives within the film industry may be a solution to decouple the historical association between Hollywood films and cigarettes.


Assuntos
Filmes Cinematográficos/história , Fumar/história , Indústria do Tabaco/história , California , Pessoas Famosas , História do Século XX , Humanos , Marketing/história
7.
Accid Anal Prev ; 35(1): 111-20, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12479902

RESUMO

This paper reports a before-and-after study which evaluated the impacts of installing and operating red light cameras at two "T" and one "X" signalized intersections on driver stopping propensity upon the onset of amber. Rather than using video cameras, a special purpose data logger working in conjunction with loop sensors was used to gather traffic parameters, vehicle stopping/crossing movements, and signal phases. Logistic modeling was employed to model the revealed stopping/crossing decisions of non-platoon vehicle drivers in response to the onset of amber with traffic, situational and behavioral variables, including their interactions. The results indicate that the variable Cam_Inst that gathered the impacts of red light camera (RLC) installation on driver decision-making at signalized intersection was significant at 5% level only for the camera approach model of the cross-intersection. The significance of Cam_Inst was undermined for the camera approaches at the T-intersections by the inclusion of a significant two-order variable defining the interaction of Cam_Inst with distance from the stop-line. One may, thus, infer that RLC has a fixed-quantum effect at the cross-intersection, but an accentuated effect with distance at the two T-intersections. Lastly, the effects of a RLC at an intersection on the stopping decision at the non-camera approaches were minimal.


Assuntos
Condução de Veículo/legislação & jurisprudência , Tomada de Decisões , Controle Social Formal , Gravação em Vídeo , Condução de Veículo/psicologia , Humanos , Aplicação da Lei/métodos , Modelos Logísticos , Razão de Chances , Singapura
8.
J Safety Res ; 33(3): 355-69, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12404998

RESUMO

PROBLEM: This paper evaluates the stopping propensity of drivers at matured in-service red light camera (RLC) signalized T-intersections after a number of years of camera operation. METHOD: A special-purpose data logger working in conjunction with loop sensors was used to gather traffic parameters, vehicle stopping/crossing movements, and signal phases at camera (treatment) and noncamera (comparison) approaches. Logistic modeling was employed to determine the stopping/crossing decisions of civilian vehicle drivers in response to the onset of yellow (amber) with traffic and the associated situational and behavioral variables, including their interactions. SUMMARY: The propensity to stop at camera approaches was about 17 times more than at noncamera approaches. This finding strongly affirmed the positive effect of RLC in encouraging drivers to stop. The likelihood to stop was about 6.5 times higher for an approach that faces an opposing right-turn conflict immediately after the onset of red. Higher stopping propensity was also more prevalent during weekdays and in periods of low traffic volumes. IMPACT ON INDUSTRY: The findings provided an objective measure on the effectiveness of RLC that would be useful to evaluate intersections for camera installation as well as on the implementation and operational aspects of RLC program.


Assuntos
Condução de Veículo/psicologia , Tomada de Decisões , Luz , Fotografação , Gestão da Segurança/métodos , Acidentes de Trânsito/prevenção & controle , Acidentes de Trânsito/psicologia , Desaceleração , Ergonomia , Humanos , Modelos Logísticos , Singapura
10.
J Environ Sci Health B ; 37(4): 355-64, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12081027

RESUMO

Laboratory studies utilizing radioisotopic techniques were conducted to determine the adsorption, desorption, and mobility of endosulfan (6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxanthiepin3-oxide) and methamidophos (O,S-dimethyl phosphorothioate) in sandy loam and clay soils of the Cameron Highlands and the Muda rice-growing area, respectively. High Freundlich adsorption distribution coefficients [Kads(f)] for endosulfan (6.74 and 18.75) and low values for methamidophos (0.40 and 0.98) were obtained in the sandy loam and clay soils, respectively. The observed Koc values for endosulfan were 350.85 (sandy loam) and 1143.19 (clay) while Koc values of 20.92 (sandy loam) and 59.63 (clay) were obtained for methamidophos. Log Kow of 0.40 and 1.25 were calculated for endosulfan as well as -1.96 and -1.21 for methamidophos in the sandy loam and clay soils, respectively. Desorption was common to both pesticides but the desorption capacity of methamidophos from each soil type far exceeded that of endosulfan. Soil thin layer chromatography (TLC) and column studies showed that while methamidophos was very mobile in both soils, endosulfan displayed zero mobility in clay soil.


Assuntos
Endossulfano/química , Inseticidas/química , Compostos Organotiofosforados/química , Solo/análise , Adsorção , Cromatografia em Camada Fina , Endossulfano/análise , Inseticidas/análise , Cinética , Malásia , Compostos Organotiofosforados/análise
11.
Osteoarthritis Cartilage ; 10(4): 308-20, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11950254

RESUMO

OBJECTIVE: The aim of this study was to examine the effects of recombinant human Fgf18 on chondrocyte proliferation and matrix production in vivo and in vitro. In addition, the expressions of Fgf18 and Fgf receptors (Fgfr) in adult human articular cartilage were examined. METHODS: Adenovirus-mediated transfer of Fgf18 into murine pinnae and addition of FGF18 to primary cultures of adult articular chondrocytes were used to assess the effects of FGF18 on chondrocytes. In situ hybridization was used to examine the expression of Fgf18 and Fgfr s in adult human articular cartilage. RESULTS: Expression of Fgf18 by adenovirus-mediated gene transfer in murine pinnae resulted in a significant increase in chondrocyte number. Chondrocytes were identified by staining with toluidine blue and a monoclonal antibody directed against type II collagen. Fgf18, Fgfr 2-(IIIc), Fgfr 3-(IIIc), and Fgfr 4 mRNAs were detected within these cells by in situ hybridization. The nuclei of the chondrocytes stained with antibodies to PCNA and FGF receptor (FGFR) 2. Addition of FGF18 to the culture media of primary articular chondrocytes increased the proliferation of these cells and increased their production of extracellular matrix. To assess the receptor selectivity of FGF18, BaF3 cells stably expressing the genes for the major splice variants of Fgfr1-3 were used. Proliferation of cells expressing Fgfr 3-(IIIc) or Fgfr 2-(IIIc) was increased by incubation with FGF18. Using FGFR-Fc fusion proteins and BaF3 cells expressing Fgfr 3-(IIIc), only FGFR 3-(IIIc)-Fc, FGFR 2-(IIIc)-Fc or FGFR 4-Fc reduced FGF18-mediated cell proliferation. Expression of Fgf18, Fgfr 3-(IIIc) and Fgfr 2-(IIIc) mRNAs was localized to chondrocytes of human articular cartilage by in situ hybridization. CONCLUSION: These data demonstrate that Fgf18 can act as a trophic factor for elastic chondrocytes and their progenitors in vivo and articular chondrocytes cultured in vitro. Expression of Fgf18 and the genes for two of its receptors in chondrocytes suggests that Fgf18 may play an autocrine role in the biology of normal articular cartilage.


Assuntos
Condrócitos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Adulto , Animais , Cartilagem Articular/química , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Condrócitos/citologia , Colágeno Tipo II/metabolismo , Orelha Externa , Feminino , Fatores de Crescimento de Fibroblastos/análise , Expressão Gênica , Técnicas de Transferência de Genes , Humanos , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Camundongos , Camundongos Nus , Proteoglicanas/metabolismo , RNA Mensageiro/análise , Receptores de Fatores de Crescimento de Fibroblastos/análise , Receptores de Fatores de Crescimento de Fibroblastos/genética , Proteínas Recombinantes/farmacologia , Suínos
12.
Bioorg Med Chem ; 9(8): 2083-91, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11504644

RESUMO

The catalytic activity of the bacterial phosphotriesterase (PTE) toward a series of chiral analogues of the chemical warfare agents sarin and soman was measured. Chemical procedures were developed for the chiral syntheses of the S(P)- and R(P)-enantiomers of O-isopropyl p-nitrophenyl methylphosphonate (sarin analogue) in high enantiomeric excess. The R(P)-enantiomer of the sarin analogue (k(cat)=2600 s(-1)) was the preferred substrate for the wild-type PTE relative to the corresponding S(P)-enantiomer (k(cat)=290 s(-1)). The observed stereoselectivity was reversed using the PTE mutant, I106A/F132A/H254Y where the k(cat) values for the R(P)- and S(P)-enantiomers were 410 and 4200 s(-1), respectively. A chemo-enzymatic procedure was developed for the chiral synthesis of the four stereoisomers of O-pinacolyl p-nitrophenyl methylphosphonate (soman analogue) with high diastereomeric excess. The R(P)R(C)-stereoisomer of the soman analogue was the preferred substrate for PTE. The k(cat) values for the soman analogues were measured as follows: R(P)R(C,) 48 s(-1); R(P)S(C), 4.8 s(-1); S(P)R(C), 0.3 s(-1), and S(P)S(C), 0.04 s(-1). With the I106A/F132A/H254Y mutant of PTE the stereoselectivity toward the chiral phosphorus center was reversed. With the triple mutant the k(cat) values for the soman analogues were found to be as follows: R(P)R(C,) 0.3 s(-1); R(P)S(C), 0.3 s(-1); S(P)R(C), 11s(-1), and S(P)S(C), 2.1 s(-1). Prior investigations have demonstrated that the S(P)-enantiomers of sarin and soman are significantly more toxic than the R(P)-enantiomers. This investigation has demonstrated that mutants of the wild-type PTE can be readily constructed with enhanced catalytic activities toward the most toxic stereoisomers of sarin and soman.


Assuntos
Substâncias para a Guerra Química/metabolismo , Esterases/metabolismo , Sarina/metabolismo , Soman/metabolismo , Arildialquilfosfatase , Substâncias para a Guerra Química/síntese química , Substâncias para a Guerra Química/química , Esterases/genética , Hidrólise , Inativação Metabólica , Cinética , Conformação Molecular , Mutagênese Sítio-Dirigida , Sarina/síntese química , Sarina/química , Soman/síntese química , Soman/química
13.
Pac Health Dialog ; 8(2): 380-7, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12180519

RESUMO

There has been increasing interest in 'awa on several levels (e.g., cultural, medicinal, economic). The present article explores the issues surrounding 'awa use, highlights existing literature, places the discussion in its proper indigenous context, and sheds light on the tensions fueled by culturally inappropriate practice. In concluding the article, recommendations within a native context are put forth in four domains: (a) education, (b) research, (c) analysis and implementation of legal protections, and (d) economic development.


Assuntos
Etnicidade , Medicina Herbária , Kava , Cultura , Educação , Havaí , Serviços de Saúde do Indígena , Humanos , Pesquisa
14.
J Bone Miner Res ; 13(2): 195-204, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9495512

RESUMO

We have derived a series of clonal cell lines from the bone marrow of p53-/- mice that represent different stages of osteoblast and adipocyte differentiation. All cell lines show indefinite growth potential (>300 population doublings) and have generation times of 12-20 h. These cell lines have been grouped into three categories. The least mature clones are heterogeneous and appear to contain a subpopulation of stem cells, which can spontaneously generate foci that contain either adipocytes or mineralizing osteoblasts. The second category of clones are homogeneous and clearly correspond to mature osteoblasts because they express high levels of the anticipated osteoblastic markers in a stable fashion and cannot differentiate into adipocytes even in the presence of inducers. The clones in the third category are the most unique. Initially they appeared to correspond to mature osteoblasts because they express alkaline phosphatase in a homogeneous manner, secrete type I collagen, show a significant cyclic adenosine monophosphate response to parathyroid hormone, secrete osteocalcin, and mineralize extensively after only 4-7 days. However, in contrast to the mature osteoblasts, these clones can be induced to undergo massive adipocyte differentiation, and this differentiation is accompanied by the complete loss of expression of all osteoblastic markers except alkaline phosphatase. These observations indicate that some cells that have acquired all of the characteristics of mature osteoblasts can be diverted to the adipocyte pathway. Further characterization of these clones may be particularly relevant to osteoporotic conditions where increased adipocyte formation appears to occur at the expense of osteoblast formation.


Assuntos
Adipócitos/citologia , Células da Medula Óssea/citologia , Osteoblastos/citologia , Adipócitos/enzimologia , Adipócitos/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Diferenciação Celular , Divisão Celular , Linhagem Celular , Colágeno/metabolismo , AMP Cíclico/metabolismo , Genes p53/genética , Membro Posterior , Masculino , Camundongos , Osteoblastos/enzimologia , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Hormônio Paratireóideo/metabolismo
15.
Am J Psychiatry ; 153(8): 1097-9, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8678183

RESUMO

OBJECTIVE: The purpose of this study was to identify specific competencies that differentiated passing from failing performance on the American Board of Psychiatry and Neurology Part II oral board certification examination. METHOD: A total of 363 candidates were rated in 18 areas of competence defined by behavioral criteria. Data were analyzed to determine which areas best discriminated between passing and failing candidates. RESULTS: In both parts of the examination, the ability to develop a comprehensive treatment plan was most influential. After that, specific interview and observational skills discriminated best. Failing candidates had most difficulty detecting and following informational and affective cues in their interview of a patient and presenting a biopsychosocial formulation and comprehensive treatment plan. CONCLUSIONS: Specific candidate competencies related to passing and failing performances can be identified and assessed by a rating scale of observable behaviors on the board certification examination in psychiatry.


Assuntos
Competência Clínica/normas , Neurologia/educação , Psiquiatria/educação , Conselhos de Especialidade Profissional/normas , Competência Clínica/estatística & dados numéricos , Humanos , Neurologia/normas , Projetos Piloto , Psiquiatria/normas , Análise de Regressão , Conselhos de Especialidade Profissional/estatística & dados numéricos
16.
Artigo em Inglês | MEDLINE | ID: mdl-8936047

RESUMO

A modified version of a previously published extraction technique using acetone as the extracting medium and separation on an HPLC equipped with a Spherisorb C18 ODS2 column packed with 3 micron particles along with a suitable flow rate and mobile phase significantly improves the resolution of the chromatographic output (fluorescence detector), allowing for accurate measurement of alpha-, delta- and gamma(+ beta)-tocopherols. It was found that two extractions of the same sample yielded approximately 97% of the total extractable alpha-tocopherol. Vitamin C was not needed as an anti-oxidant to protect alpha-tocopherol during extraction from chicken liver but was needed when using fish liver. alpha-tocopherol was found not to be evenly distributed in beef, chicken or fish liver.


Assuntos
Bovinos/metabolismo , Galinhas/metabolismo , Peixes/metabolismo , Fígado/efeitos dos fármacos , Oncorhynchus mykiss/metabolismo , Vitamina E/análise , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Cromatografia Líquida de Alta Pressão , Fígado/metabolismo , Reprodutibilidade dos Testes , Especificidade da Espécie , Vitamina E/análogos & derivados
17.
Cancer Res ; 53(13): 3098-102, 1993 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-8319217

RESUMO

Using a well-defined in vitro model system for neoplastic progression, we have examined two basic characteristics in the acquisition of amplification potential. Since Syrian hamster embryo fibroblasts can be transformed by a variety of methods (spontaneously, chemically, virally, or by transfection with oncogenes), we determined whether the method of transformation affects the capability of a cell to amplify. In addition, since variants can be isolated from cell populations as they progress toward tumorigenicity, we can monitor changes in amplification potential during this multistep process. We find that the capability to amplify is independent of the method of transformation and that the acquisition of this ability occurs in a defined step in the transformation process. In this model system, acquisition of amplification ability occurred concomitantly with the loss of tumor suppression function.


Assuntos
Carcinógenos/toxicidade , Transformação Celular Neoplásica/genética , Fibroblastos/fisiologia , Fibrossarcoma/genética , Amplificação de Genes/genética , Lesões Pré-Cancerosas/genética , Animais , Antineoplásicos/farmacologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/farmacologia , Transformação Celular Viral/genética , Cricetinae , DNA de Neoplasias/efeitos dos fármacos , DNA de Neoplasias/genética , Resistência a Medicamentos , Embrião de Mamíferos , Hibridização in Situ Fluorescente , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oncogenes/genética , Ácido Fosfonoacéticos/análogos & derivados , Ácido Fosfonoacéticos/farmacologia , Transfecção , Células Tumorais Cultivadas
18.
Virology ; 177(2): 634-45, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2164727

RESUMO

A panel of 26 temperature-sensitive mutants of MHV-A59 were selected by mutagenesis with either 5-fluorouracil or 5-azacytidine. Complementation analysis revealed the presence of one RNA+ and five RNA- complementation groups. None of the RNA- complementation groups transcribed detectable levels of positive- or negative-stranded RNA at the restrictive temperature. Temperature shift experiments after the onset of mRNA synthesis revealed at least two classes of RNA- mutants. RNA- complementation groups A, B, D, and E were blocked in the ability to release infectious virus and transcribe mRNA and genome, while group C mutants continued to release infectious virus and transcribe both mRNA and genome. Temperature shift experiments at different times postinfection suggest that the group C mutants encode a function required early in viral transcription which affects the overall rate of positive strand synthesis. Analysis of steady state levels of negative strand RNA after the shift indicate that the group C mutants were probably blocked in the ability to synthesize additional minus strand RNA under conditions in which the group E mutants continued low levels of minus strand synthesis. These data suggest that at least four cistrons may be required for positive strand synthesis while the group C cistron functions during minus strand synthesis.


Assuntos
Genes Virais , Vírus da Hepatite Murina/genética , RNA Viral/biossíntese , Transcrição Gênica , Proteínas Estruturais Virais/genética , Animais , Linhagem Celular , Teste de Complementação Genética , Cinética , Células L/metabolismo , Camundongos , Vírus da Hepatite Murina/crescimento & desenvolvimento , Mutação , Fenótipo , RNA Viral/genética , Temperatura
20.
Proc Natl Acad Sci U S A ; 86(23): 9441-5, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2687881

RESUMO

It has been hypothesized that genomic fluidity is an important component of tumorigenesis. Previous studies described the relationship between tumorigenicity and one marker for genomic fluidity, gene amplification. In this report, these studies are extended with the rat liver epithelial cell lines to show that: (i) the amplification in these cells arises in a spontaneous fashion in the population (i.e., the variants detected are not preexisting in the population), and (ii) the rate of spontaneous amplification (mutation), as measured by Luria-Delbrück fluctuation analysis, is significantly lower in the nontumorigenic cells than in the tumorigenic cells. The rate was estimated by using the Po method and the method of means. The rate of spontaneous amplification of the gene encoding the multifunctional protein CAD (containing the enzymatic activities carbamoyl-phosphate synthase, aspartate transcarbamylase, and dihydroorotase) in the highly tumorigenic cells was significantly greater than that for the nontumorigenic cells, reaching almost 1 x 10(-4) events per cell per generation. The rate of this mutagenic event is high compared to the rate of point mutations usually reported in mammalian cells, and its potential contribution to the tumorigenic process will be discussed.


Assuntos
Amplificação de Genes/fisiologia , Mutação , Células Tumorais Cultivadas/fisiologia , Animais , Antineoplásicos/farmacologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/farmacologia , Linhagem Celular , Células Clonais , Resistência a Medicamentos/genética , Técnicas Genéticas , Fígado/fisiologia , Ácido Fosfonoacéticos/análogos & derivados , Ácido Fosfonoacéticos/farmacologia , Ratos
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