Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 57
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nat Genet ; 24(3): 236-44, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10700175

RESUMO

We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to integrate large databases on gene expression and molecular pharmacology.


Assuntos
Antineoplásicos/farmacologia , DNA Complementar/genética , Bases de Dados Factuais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos , Células Tumorais Cultivadas/metabolismo , Antineoplásicos/classificação , Análise por Conglomerados , DNA de Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Especificidade de Órgãos , Células Tumorais Cultivadas/classificação
2.
Polymers (Basel) ; 15(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36679226

RESUMO

Polypropylene (PP) plastic packaging waste consists of a variety of different plastic packaging products with a great span in rheological and mechanical behavior. Therefore, the resulting post-consumer recyclates usually show melt mass-flow rates (MFR) in the region of injection molding grades and intermediate mechanical properties. High-quality packaging applications demand a distinct property profile that is met by tailor-made PP grades and cannot be met by recyclates with intermediate performance. One such application with high market volume is high-stiffness thermoforming trays. The aim of this research was to blend intermediate-performance recyclates with a virgin PP grade to obtain compounds that fulfill the rheological and mechanical demands of this application. Three commercially available PP post-consumer recyclates were acquired and compounded with different blending ratios with a high stiffness, low MFR virgin PP grade. As the pure recyclates show different rheological properties, the blending ratios had to be adapted for each of them to fit into the MFR range of 2-4 g/10 min which is desirable for thermoforming applications. The resulting PP recyclate compounds show a distinct correlation of recyclate content with rheological and mechanical performance. However, the resulting property profile was directly dependent on the performance of the originally used recyclate. The best-performing recyclate could be used in a blending ratio of 65 m% recyclate content while adhering to both property limits, the MFR of 2-4 g/10 min and the lower bound tensile stiffness of 1500 MPa.

3.
Appl Opt ; 51(20): 4833-40, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22781262

RESUMO

With one measurement configuration, existing gloss measurement methodologies are generally restricted to specific gloss levels. A newly developed image-analytical gloss parameter called "clarity" provides the possibility to describe the perceptual result of a broad range of different gloss levels with one setup. In order to analyze and finally monitor the perceived gloss of products, a fast and flexible method also for the automated inspection is highly demanded. The clarity parameter is very fast to calculate and therefore usable for fast in-line surface inspection. Coated metal specimens were deformed by varying degree and polished afterwards in order to study the clarity parameter regarding the quantification of varying surface gloss types and levels. In order to analyze the correlation with the human gloss perception a study was carried out in which experts were asked to assess gloss properties of a series of surface samples under standardized conditions. The study confirmed clarity to exhibit considerably better correlation to the human perception than alternative gloss parameters.

4.
Polymers (Basel) ; 15(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36616396

RESUMO

The transition to a circular economy has a major impact on waste management and the reuse of materials. New mandatory recycling targets for plastics will lead to a high availability of recyclates. For these recyclates, useful applications need to be found. One potential application for recyclates is blow molding bottles as packaging for non-food contents. This study investigates commercially available post-consumer high-density polyethylene recyclates together with virgin blow molding grades in terms of their short-term mechanical properties and environmental stress cracking resistance. While the short-term mechanical properties showed only slightly lower performance than the tested virgin grades, the overall environmental stress cracking failure times of the recyclates were much lower compared to virgin materials, even though the crack-growth kinetics could be similar. Although neither the tensile nor the notched impact strength results of the two polyethylene recyclates revealed large differences, the stress intensity-factor-dependent crack-growth rates of both materials were significantly different.

5.
Polymers (Basel) ; 14(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36501629

RESUMO

The high recycling targets set by the European Commission will create an increased availability of polypropylene (PP) post-consumer recyclates (PCRs). However, no regulations mandate the use of recycled PP (rPP), so the industry is challenged to explore possibilities to utilize such materials. One option, as suggested by the European Commission, is the introduction of rPP in pipe applications. According to existing standards, the use of recyclate is not allowed in pressurized gas and drinking water systems. However, many other pipe and underground applications, such as stormwater systems, open the increased use of PCRs. Additionally, even for less-demanding applications, such as non-pressure sewage systems, highly durable solutions are needed to cover the requested lifetime and request an ambitious property profile to fulfill the application needs that cannot be met by PP packaging materials and even less by PCRs thereof. Hence, this work explores the possible use of commercially available PCRs out of polypropylene from packaging applications in compounds together with virgin PP pipe grades to meet the demands for less-demanding applications. Two different commercially available rPPs and one commercially available recycled polyolefin (rPO) from mixed polyethylene and PP waste were acquired and, together with two predefined virgin PP pipe grades, were blended to compounds in the range of 10 m%, 20 m%, and 30 m% recyclate content. The compounds and three virgin PP pipe grades, acting as benchmarks, were tested in terms of short- and long-term mechanical performance as well as for many other physical properties. All of the compounds showed good results regarding fatigue crack (FCG) resistance with virgin polymer as the reference. The factors influencing FCG resistance, such as melt flow rate and polyolefin cross-contamination, were thoroughly investigated as the used virgin grades and recyclates cover a broad range of these properties.

6.
Polymers (Basel) ; 14(8)2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35458330

RESUMO

The polymer industry is pushed to present solutions that lead to a circular plastics economy. High plastic packaging waste recycling targets will eventually lead to a high availability of packaging material recyclates. Although the use of polyethylene terephthalate (PET) recyclates is prescribed by regulations to be used in new PET bottles, no such regulation prescribes the use of polyethylene recyclate (rPE) in new products. One possibility of using rPE, which is considered by the European Union, is the use within pipe materials. Pipe applications demand a certain property profile, most prominently a high slow crack growth (SCG) resistance, which is not met by most packaging materials or recyclates made from it. Hence, this work investigates the use of commercially available post-consumer recyclates out of high-density polyethylene from packaging applications in compounds together with high SCG-resistant virgin PE pipe material with a PE100-RC specification. Two rPEs were acquired from German producers and blended to compounds consisting of 25 m%, 50 m% and 75 m% recyclate. These compounds, together with the pure recyclates and several virgin pipe materials acting as benchmarks were tested in terms of short- and long-term mechanical performance and with other basic characterization methods. Several compounds exceeded the performance of one tested virgin PE pipe material, an injection molding PE80 grade, in several categories. The content of recyclate needed to outperform this benchmark grade was mostly dependent on the resulting melt flow rate (MFR) of the compound and thus also of the MFR of the pure recyclate. Furthermore, different levels of polypropylene contaminations within the recyclates resulted in differently contaminated compounds. This is proved to influence the SCG resistance too, as compounds of similar MFRs but with different SCG resistances were found.

7.
Polymers (Basel) ; 13(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068974

RESUMO

The current efforts in moving closer towards a circular plastics economy puts massive pressure on recycled plastics, especially recycled polyethylene (rPE) and recycled polypropylene (rPP) to enter new markets. Their market penetration remained low so far, despite PE and PP constituting the largest share of plastic wastes. However, with the current imperative of more circularity comes a new focus on performance of recyclates. Hence, a detailed understanding of composition and structure-property relationships of post-consumer recyclates has to be developed. Five recycling companies from the Austrian and German markets were asked to supply their purest high-quality rPE and rPP grades. These were characterized by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), and Fourier-transform infrared (FTIR) spectroscopy, and micro-imaging. Technological characterization included density measurements, determination of the melt flow rate (MFR), and Charpy impact testing. All recyclates contained diverse contaminants and inclusions ranging from legacy fillers like calcium carbonate to polymeric contaminants like polyamides or polyolefin cross-contamination. The overall amount, size, and distribution of contaminants varied significantly among suppliers. Furthermore, first structure-property relationships for polyolefin recyclates that link inorganic content and polymeric purity with density and impact performance could be derived.

8.
Scand J Gastroenterol ; 45(12): 1449-56, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20653489

RESUMO

OBJECTIVE: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). MATERIAL AND METHODS: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. RESULTS: Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. CONCLUSION: Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Fidelidade a Diretrizes , Garantia da Qualidade dos Cuidados de Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Estudos Retrospectivos
9.
Polymers (Basel) ; 11(6)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167458

RESUMO

Polypropylene random copolymers (PP-R) are common materials for pressurized hot water pipes. In many pipe systems, potable water is disinfected by chlorine to prevent waterborne diseases. This paper deals with hot chlorinated water induced aging of two PP-R grades with varying morphology. One material had a conventional monoclinic α crystal form (PP-Rα), whereas the other was explicitly beta-nucleated resulting in a trigonal ß crystal form with a fine spherulite structure (PP-Rß). Micro-sized specimens with a thickness of 100 µm were used for aging experiments at 60 °C in chlorinated water with 5 mg/L free chlorine, and aging indicators were monitored for exposure times of up to 2000 h. On the other hand, superimposed mechanical-environmental tests were carried out by using cracked round bar specimens with a diameter of 14 mm to determine the fatigue crack growth (FCG) resistance of both PP-R grades at 60 °C in non-chlorinated and chlorinated water. PP-Rß was found to outperform PP-Rα with an about 30% higher time-to-embrittlement value of 2000 h. Furthermore, PP-Rß exhibited an enhanced FCG resistance in both non-chlorinated and chlorinated water. The effect of chlorine content on the deterioration of the FCG resistances was significantly more pronounced for PP-Rα.

10.
Polymers (Basel) ; 11(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288492

RESUMO

The influence of chlorinated water on the global and local aging behavior of polypropylene (PP) was investigated for three differently stabilized PP grades consisting of the same PP base polymer. While one of the PP grades contained only a processing stabilizer (PP-S0), the other two were modified with a primary phenolic antioxidant (PP-S1) and a combination of a primary phenolic antioxidant and a hindered amine stabilizer (PP-S3). To study global aging effects, micro-sized specimens were pre-exposed to chlorinated water (5 mg/L free chlorine) at 60 °C for up to 750 h. Over the entire exposure period, significant material aging was detected by monitoring a continuous decrease in stabilizer content, oxidation induction temperature, mean molar mass, and mechanical strain at break. In terms of aging resistance and ultimate mechanical performance, PP-S1 was found to outperform the other two material formulations under these test conditions. Moreover, superimposed mechanical-environmental fatigue tests with cracked round bar specimens were carried out with the three PP grades in non-chlorinated (0 mg/L free chlorine) and chlorinated (5 mg/L free chlorine) water at 80 °C and 95 °C to study local crack tip aging effects. While the fatigue crack growth resistance substantially deteriorated for all three materials in chlorinated water, a significantly stronger effect was found for the higher temperature, with crack growth rates at a given stress intensity factor range in chlorinated water being ca. 30 to 50 times faster than in non-chlorinated water, depending on the material. Molar mass measurements of material samples taken from various positions of the tested CRB specimens provided clear evidence of enhanced local crack tip aging due to the chlorinated water environment.

11.
Eur J Gastroenterol Hepatol ; 20(8): 740-7, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18617778

RESUMO

BACKGROUND: Earlier studies have documented that the prevalence of decreased bone mineral density (BMD) is elevated in patients with inflammatory bowel disease. The objective of this study was to investigate the prevalence of vertebral deformities in inflammatory bowel disease patients and their relation with BMD and bone turnover. METHODS: One hundred and nine patients with Crohn's disease (CD) and 72 with ulcerative colitis (UC) (age 44.5+/-14.2 years) were studied. BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single energy densitometry of the spine for assessment of vertebral deformities was performed. Serum markers of bone resorption (carboxy-terminal cross-linked telopeptide of type I collagen) and formation (procollagen type I amino-terminal propeptide) were measured, and determinants of prevalent vertebral deformities were assessed using logistic regression analysis. RESULTS: Vertebral deformities were found in 25% of both CD and UC patients. Comparing patients with and without vertebral deformities, no significant difference was found between Z-scores and T-scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of type I collagen and serum procollagen type I amino-terminal propeptide. Using logistic regression analysis the only determinant of any morphometric vertebral deformity was sex. The presence of multiple vertebral deformities was associated with older age and glucocorticoid use. CONCLUSION: The prevalence of morphometric vertebral deformities is high in CD and UC. Male sex, but neither disease activity, bone turnover markers, clinical risk factors, nor BMD predicted their presence. The determinants for having more than one vertebral deformity were age and glucocorticoid use. This implies that in addition to screening for low BMD, morphometric assessment of vertebral deformities is warranted in CD and UC.


Assuntos
Doenças Inflamatórias Intestinais/complicações , Fraturas da Coluna Vertebral/etiologia , Absorciometria de Fóton , Adulto , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Reabsorção Óssea/etiologia , Reabsorção Óssea/fisiopatologia , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Estudos Transversais , Feminino , Fraturas do Quadril/etiologia , Fraturas do Quadril/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Curvaturas da Coluna Vertebral/etiologia , Curvaturas da Coluna Vertebral/fisiopatologia , Fraturas da Coluna Vertebral/fisiopatologia
12.
Polymers (Basel) ; 10(9)2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30960893

RESUMO

Polyamide 66 (PA 66) and short glass fiber reinforced versions of PA 66 are widely used for solar-thermal applications, in which thermal and environmental loading of components is from high importance. In this study, the influence of crosslinking via electronic beam irradiation on the morphology and mechanical behavior of unreinforced PA 66 and two types of short glass fiber reinforced PA 66 (30 wt % glass fiber content, 35 wt % glass fiber content) was investigated. In total, five different electronic beam irradiation doses in the range of 0 and 200 kGy were applied. Besides experiments with unconditioned specimens, also preconditioned specimens saturated with water at 80 °C for seven days were investigated. It was found that irradiation causes a shift to lower melting temperatures and lower melting enthalpies, while simultaneously leading to higher glass transition temperatures (TG), increasing small strain modulus values and higher tensile strengths. Also, as expected, preconditioning samples in water at 80 °C to water uptake saturation leads to a shift to lower TG values ('plasticization' effect). In terms of tensile behavior at room temperature, water saturated specimens (being above TG at room temperature) exhibited lower modulus and tensile strength values compared to quasi-dry specimens (being below TG at room temperature).

13.
Polymers (Basel) ; 10(8)2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30960754

RESUMO

To assess the potential use of polyamide (PA) for solar-thermal systems applications, the effect of water with varying chlorine content on the fatigue crack growth (FCG) resistance of two PA formulations differing in their stabilizer packages was investigated at 80 °C. A commercial PA containing 30 wt % glass fibers and a standard stabilization package (PA-0) was used as the reference material. For the other formulation, the reference material PA-0 was compounded with two additional stabilizers (PA-S1). Keeping the specimen geometry and initial loading conditions the same, the total number of cycles to ultimate specimen failure was found to be reduced with an increase in chlorine content for both materials. As to the effect of the chlorine content on crack growth kinetics, the most pronounced effect in enhancing the crack growth rates or decreasing the FCG resistance was determined between 0 ppm and 1 ppm chlorine content. When comparing the relative change of FCG resistance in chlorinated water (10 ppm) to the FCG resistance in non-chlorinated water (0 ppm), the additional stabilization in the material PA-S1 appears beneficial over the stabilization in the reference material PA-0.

14.
J Clin Invest ; 91(1): 153-9, 1993 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8380810

RESUMO

Expression of the vascular permeability factor/vascular endothelial growth factor (VEGPF) gene was investigated in human central nervous system (CNS) neoplasms and normal brain. Adsorption of capillary permeability activity from human glioblastoma multiforme (GBM) cell conditioned medium and GBM cyst fluids by anti-VEGPF antibodies demonstrated that VEGPF is secreted by GBM cells and is present in sufficient quantities in vivo to induce vascular permeability. Cloning and sequencing of polymerase chain reaction-amplified GBM and normal brain cDNA demonstrated three forms of the VEGPF coding region (567, 495, and 363 nucleotides), corresponding to mature polypeptides of 189, 165, and 121 amino acids, respectively. VEGPF mRNA levels in CNS tumors vs. normal brain were investigated by the RNase protection assay. Significant elevation of VEGPF gene expression was observed in 81% (22/27) of the highly vascular and edema-associated CNS neoplasms (6/8 GBM, 8/8 capillary hemangioblastomas, 6/7 meningiomas, and 2/4 cerebral metastases). In contrast, only 13% (2/15) of those CNS tumors that are not commonly associated with significant neovascularity or cerebral edema (2/10 pituitary adenomas and 0/5 nonastrocytic gliomas) had significantly increased levels of VEGPF mRNA. The relative abundance of the forms of VEGPF mRNA was consistent in tumor and normal brain: VEGPF495 > VEGPF363 > VEGPF567. In situ hybridization confirmed the presence of VEGPF mRNA in tumor cells and its increased abundance in capillary hemangioblastomas. Our results suggest a significant role for VEGPF in the development of CNS tumor neovascularity and peritumoral edema.


Assuntos
Neoplasias Encefálicas/genética , Encéfalo/metabolismo , Neoplasias do Sistema Nervoso Central/genética , Fatores de Crescimento Endotelial/análise , Fatores de Crescimento Endotelial/genética , Linfocinas/análise , Linfocinas/genética , RNA Mensageiro/metabolismo , Sequência de Bases , Southern Blotting , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Epilepsia/genética , Epilepsia/metabolismo , Epilepsia/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Hemangiossarcoma/genética , Hemangiossarcoma/metabolismo , Hemangiossarcoma/patologia , Humanos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Meningioma/genética , Meningioma/metabolismo , Meningioma/patologia , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Sondas de Oligonucleotídeos , RNA Mensageiro/análise , RNA Mensageiro/genética , Mapeamento por Restrição , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
15.
Mol Cell Biol ; 15(6): 3041-8, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7760800

RESUMO

We demonstrated that MIF-1, identified initially as a binding activity that associated with the intron I element of the c-myc gene, consists of two polypeptides, the myc intron-binding peptide (MIBP1) and the major histocompatibility class II promoter-binding protein, RFX1. Using a polyclonal antiserum directed against either oligonucleotide affinity-purified MIBP1 or a peptide derived from RFX1, we showed that MIBP1 and RFX1 are distinct molecules that associate in vivo and are both present in DNA-protein complexes at the c-myc (MIF-1) and major histocompatibility complex class II (RFX1) binding sites. We have also found that MIBP1 and RFX1 bind to a regulatory site (termed EP) required for enhancer activity of hepatitis B virus. In addition, we have identified MIF-1-like sequences within regulatory regions of several other viral genes and have shown that MIBP1 binds to these sites in cytomegalovirus, Epstein-Barr virus, and polyomavirus. We have also demonstrated that the MIF-1 and EP elements can function as silencers in the hepatocarcinoma HepG2 and the cervical carcinoma HeLa cell lines. These findings indicate that MIBP1 and EP/RFX1 can associate in vivo and may regulate the expression of several distinct cellular and viral genes.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Vírus da Hepatite B/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Bases , Sítios de Ligação , Regulação Viral da Expressão Gênica , Vírus da Hepatite B/genética , Íntrons , Dados de Sequência Molecular , Plasmídeos , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myc/química , Fatores de Transcrição de Fator Regulador X
16.
Scand J Gastroenterol Suppl ; (243): 46-54, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16782622

RESUMO

OBJECTIVE: To give a general outline of a 10-year clinical follow-up study of a population-based European cohort of inflammatory bowel disease (IBD) patients and to present the first results in terms of clinical outcome parameters and risk factors. MATERIALS AND METHODS: A population-based cohort of newly, prospectively, diagnosed cases was initiated between 1991 and 1993. The 2201 patients with IBD (706 had Crohn's disease (CD), 1379 had ulcerative colitis (UC) and 116 had indeterminate colitis) originated from 20 different areas in 11 different European countries and Israel. For the 10-year follow-up of this cohort, electronic data-collecting instruments were made available through an Internet-based website. Data concerning vital status, disease activity, medication use, surgical events, cancer, pregnancy, fertility, quality of life and health-care costs were gathered. A blood sample was obtained from patients and controls to perform genotypic characterization. RESULTS: Thirteen centres from eight European countries and Israel participated. In 958 (316 CD and 642 UC) out of a total of 1505 IBD patients (64%) from these 13 centres, a complete dataset was obtained at follow-up. Even though an increased mortality risk was observed in CD patients 10 years after diagnosis, a benign disease course was observed in this patient group in terms of disease recurrence. A correlation between ASCA and CARD15 variants in CD patients and complicated disease course was observed. A north-south gradient was observed regarding colectomy rates in UC patients. Direct costs were found to be highest in the first year after diagnosis and greater in CD patients than in UC patients, with marked differences between participating countries. CONCLUSIONS: This 10-year clinical follow-up study of a population-based European cohort of IBD patients provides updated information on disease outcome of these patient groups.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Adulto , Inteligência Artificial , Colectomia , Colite Ulcerativa/economia , Colite Ulcerativa/genética , Colite Ulcerativa/cirurgia , Comunicação , Doença de Crohn/economia , Doença de Crohn/genética , Doença de Crohn/cirurgia , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Genótipo , Custos de Cuidados de Saúde , Humanos , Internet , Israel/epidemiologia , Masculino , Proteína Adaptadora de Sinalização NOD2/genética , Fenótipo , Relações Médico-Paciente , Polimorfismo Genético , Estudos Prospectivos , Recidiva , Fatores de Risco
17.
Clin Cancer Res ; 4(4): 1047-54, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9563901

RESUMO

In the present study, we report our findings on the impact of p53 disruption on the sensitivity of human cell lines to the antimitotic agents Taxol and vincristine. Comparisons of cell survival and apoptosis were made with y-irradiation and, in some cases, several other DNA-damaging chemotherapeutic agents. Studies in eight Burkitt's lymphoma and lymphoblastoid cell lines (four wild-type p53 and four mutant p53 cell lines) revealed that the DNA-damaging agents assayed tended to exhibit less growth inhibition in the mutant p53 cell lines compared to the wild-type p53 cell lines. In contrast, no significant correlation was apparent between p53 gene status and the growth-inhibitory potency of Taxol or vincristine in these eight cell lines. We also found that contrary to gamma-irradiation, Taxol and vincristine could induce apoptosis in lymphoma cell lines harboring p53 mutations. These observations were explored further in lymphoblastoid VDSO cells (wild-type p53) from a normal individual and stably transfected VDSO derivatives lacking p53 function due to expression of the human papillomavirus type-16 E6 gene. We found that p53 disruption in VDSO/E6 cells blocked y-ray-induced apoptosis and afforded a survival advantage to VDSO/E6 cells compared to control-transfected cells. In contrast, p53 disruption did not affect Taxol- or vincristine-induced apoptosis or survival in VDSO cells. The effect of p53 disruption on Taxol sensitivity was explored further in the breast carcinoma MCF-7 and colon carcinoma HCT-116 cell lines that had been stably transfected with either the human papillomavirus type-16 E6 gene or a dominant-negative mutant p53 gene. Again, in these cell model systems, we found that p53 disruption did not affect the growth-inhibitory potency of Taxol. Taken together, our results suggest that p53 status is not a dominant factor in the mechanism by which antimitotic agents induce apoptosis and reduce survival in immortalized human cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Genes p53/fisiologia , Paclitaxel/farmacologia , Vincristina/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/metabolismo , Neoplasias do Colo/metabolismo , Relação Dose-Resposta a Droga , Genes p53/genética , Humanos , Linfoma/metabolismo , Mutação , Radiação Ionizante , Células Tumorais Cultivadas/efeitos dos fármacos
18.
World J Gastroenterol ; 11(45): 7152-8, 2005 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-16437663

RESUMO

AIM: To describe an Internet-based data acquisition facility for a European 10-year clinical follow-up study project of a population-based cohort of inflammatory bowel disease (IBD) patients and to investigate the influence of demographic and disease related patient characteristics on response rates. METHODS: Thirteen years ago, the European Collaborative study group of IBD (EC-IBD) initiated a population-based prospective inception cohort of 2 201 uniformly diagnosed IBD patients within 20 well-described geographical areas in 11 European countries and Israel. For the 10-year follow-up of this cohort, an electronic patient questionnaire (ePQ) and electronic physician per patient follow-up form (ePpPFU) were designed as two separate data collecting instruments and made available through an Internet-based website. Independent demographic and clinical determinants of ePQ participation were analyzed using multivariate logistic regression. RESULTS: In 958 (316 CD and 642 UC) out of a total number of 1 505 (64%) available IBD patients, originating from 13 participating centers from nine different countries, both ePQ and ePpPFU were completed. Patients older than 40 years at ePQ completion (OR: 1.53 (95%CI: 1.14-2.05)) and those with active disease during the 3 mo previous to ePQ completion (OR: 3.32 (95%CI: 1.57-7.03)) were significantly more likely to respond. CONCLUSION: An Internet-based data acquisition tool appeared successful in sustaining a unique Western-European and Israelian multi-center 10-year clinical follow-up study project in patients afflicted with IBD.


Assuntos
Doenças Inflamatórias Intestinais , Adulto , Estudos de Coortes , Interpretação Estatística de Dados , Europa (Continente) , Feminino , Seguimentos , Humanos , Internet , Israel , Masculino , Inquéritos e Questionários
19.
Virus Res ; 9(2-3): 249-61, 1988 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2833048

RESUMO

Our laboratory previously identified and preliminarily mapped 58 viral RNA transcripts in varicella zoster virus (VZV) infected cells (Ostrove et al., 1985). This study was initiated to more precisely map these transcripts, to identify additional transcripts, and to determine transcript directionality. To accomplish this, 32 overlapping BamHI, EcoRI, and SmaI fragments representing 99.7% of the genome were cloned into pGEM-2, a plasmid which contains a multiple cloning site flanked by SP6 and T7 RNA polymerase promoters. Each of these clones was used to produce 32P-labeled double-stranded DNA probes to detect transcripts homologous to either strand of the VZV insert, and single-stranded [32P]RNA probes in order to detect RNAs of either polarity. These probes were hybridized to Northern blots of VZV-infected cell RNA. In all, 77 RNAs were detected with both DNA and RNA probes. The direction of transcription and localization of 57 of the 58 previously identified RNAs and of 20 newly recognised abundant transcripts were determined. Thirty-three additional low-abundance transcripts were detected only by the relatively more sensitive RNA probes. A map indicating the directionality and approximate locations of the abundant VZV transcripts was constructed.


Assuntos
Herpesvirus Humano 3/genética , RNA Viral/genética , Transcrição Gênica , Mapeamento Cromossômico , Clonagem Molecular , Hibridização de Ácido Nucleico
20.
Inflamm Bowel Dis ; 8(6): 382-9, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12454613

RESUMO

INTRODUCTION: Inflammatory bowel diseases are chronic conditions that might cause a severe impact on social life. The aim of the study was to assess employment, chronic work disability, and sick leave in patients with inflammatory bowel disease. METHODS: A postal questionnaire was sent to 984 patients with inflammatory bowel disease and 1504 controls. Age- and gender-adjusted employment and chronic work disability ratios and rates were calculated using indirect standardization. In subjects in paid employment, proportions of those having an episode of sick leave and lost workdays were analyzed. Logistic regression was used to assess the contribution of age, gender, education, and course of disease. RESULTS: The results of 680 (69%) patients and 715 (48%) controls could be analyzed. For the entire group of patients, employment was 6.5% lower, compared with controls (95% CI: 4.0-9.0). Chronic work disability was 17.1% higher than expected (95% CI: 15.1-19.1). In those in paid employment, 62% of patients compared with 53% of controls had experienced one or more episodes of sick leave during the past year (p = 0.002). This resulted in 19.2 versus 11.8 days of sick leave per subject per year for patients and controls respectively (p = 0.002). Relative to controls, the risk of chronic work disability was more increased in younger (p = 0.02) and higher educated (p = 0.02) patients. Course of disease contributed to chronic work disability and sick leave. CONCLUSION: IBD has a significant impact on labor force participation that is higher in CD compared with UC and highest in younger and more highly educated patients.


Assuntos
Avaliação da Deficiência , Emprego/estatística & dados numéricos , Doenças Inflamatórias Intestinais/complicações , Licença Médica/estatística & dados numéricos , Adolescente , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Escolaridade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Classe Social
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA