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Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.
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Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Neoplasias Hepáticas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hepatitis C Crónica/epidemiología , Humanos , Incidencia , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
We demonstrate the transmission of 51.56-Gb/s on-off keying (OOK) signals generated by using a 1.55-µm directly modulated laser (DML) over 15-km long standard single-mode fiber. In this experiment, a duobinary electrical equalizer based on a finite-impulse-response filter is used at the receiver to increase the dispersion-limited transmission distance. We evaluate the performances of the 51.56-Gb/s OOK signals with respect to the transmission distance by using the frequency response analysis of the proposed system. This result is used to explain why it is effective to utilize the duobinary equalization (instead of binary equalization) for increasing the transmission distance.
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BACKGROUND AND OBJECTIVE: Daidzein is an isoflavone abundant in soybeans, kudzu root and red clover, which have been widely studied for its therapeutic potential. The present study was designed to evaluate the effects of daidzein on alveolar bone loss and internal microstructures of bone in a rat model of experimental periodontitis by assessing morphological data obtained from micro-computed tomography (micro-CT). MATERIAL AND METHODS: Twenty-four male Sprague-Dawley rats were randomly assigned to the following three groups comprising eight animals each: the nonligation (NL) group; the ligation (L) group; and the ligation+daidzein (LD) group. To induce periodontitis, a 4-0 braided silk ligature was tied around the cervical area of the lower-right first molars of rats in groups L and LD. Rats in the LD group were given daily doses of daidzein (10 mg/kg of body weight) by intraperitoneal injection immediately after ligature placement. Two weeks after the placement of ligatures, mandibular block biopsies were scanned using a micro-CT system. RESULTS: Daily administration of daidzein strongly suppressed the ligature-induced loss of alveolar bone height. In addition, when rats were treated with daidzein, the ligature-induced decrease in the bone volume fraction was significantly recovered. Furthermore, daidzein significantly reversed ligature-induced deteriorations in the microarchitecture parameters of trabecular bone, such as trabecular thickness, bone mineral density, trabecular separation and structure model index. CONCLUSION: The study presented here demonstrates, for the first time, that daidzein effectively reduces alveolar bone destruction resulting from experimental periodontitis in rats. Further studies are necessary for the translation of this compound clinically to improve the outcomes of patients diagnosed with periodontitis.
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Periodontitis , Pérdida de Hueso Alveolar/inducido químicamente , Animales , Densidad Ósea , Masculino , Ratas , Ratas Sprague-Dawley , Microtomografía por Rayos XRESUMEN
We analyze the inter-core crosstalk in homogeneous multi-core two-mode fibers (MC-TMFs) under bent condition by using the coupled-mode equations. In particular, we investigate the effects of the intra-core mode coupling on the inter-core crosstalk for two different types of MC-TMFs at various bending radii. The results show that the inter-core homo-mode crosstalk of LP(11) mode is dominant under the gentle fiber bending condition due to its large effective area. However, as the fiber bending becomes tight, the intra-core mode coupling is significantly enhanced and consequently makes all the inter-core crosstalk levels comparable to each other regardless of the mode. A similar tendency is observed at a reduced bending radius when the difference in the propagation constants between modes is large and core pitch is small.
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Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in humans and rats with liver cirrhosis (LC) and diabetes mellitus (DM), alone and in combination (LCD) did not seem to be reported. Sildenafil was administered intravenously (10 mg/kg) and orally (20 mg/kg) to control, LC, DM, and LCD rats. Expression of intestinal CYP isozymes in those rats was also measured. In LC, DM, and LCD rats, the areas under the curve (AUCs) of intravenous sildenafil were significantly greater (by 195%, 54.2%, and 127%, respectively) than controls. In LC and LCD rats, AUCs of oral sildenafil were significantly greater (3010% and 2030%, respectively) than controls. In LC, DM, and LCD rats, significantly greater AUCs of intravenous sildenafil were due to the slower hepatic extraction of sildenafil (because of decrease in the protein expression of hepatic CYP2C11 and 3A subfamily in LC and LCD rats, and CYP2C11 in DM rats). In LC and LCD rats, greater magnitude of increase in AUCs of oral sildenafil than those after the intravenous administration could be mainly due to the decrease in the intestinal extraction of sildenafil (because of decrease in the protein expression of intestinal CYP2C11 in LC and LCD rats).
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Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Cirrosis Hepática/complicaciones , Cirrosis Hepática/metabolismo , Piperazinas/farmacocinética , Sulfonas/farmacocinética , Vasodilatadores/farmacocinética , Administración Oral , Animales , Proteínas Sanguíneas/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Immunoblotting , Inyecciones Intravenosas , Intestinos/enzimología , Masculino , Microsomas Hepáticos/metabolismo , Piperazinas/administración & dosificación , Piperazinas/sangre , Piperazinas/química , Unión Proteica , Purinas/administración & dosificación , Purinas/sangre , Purinas/química , Purinas/farmacocinética , Ratas , Ratas Sprague-Dawley , Citrato de Sildenafil , Sulfonas/administración & dosificación , Sulfonas/sangre , Sulfonas/química , Vasodilatadores/administración & dosificación , Vasodilatadores/sangre , Vasodilatadores/químicaRESUMEN
Hepatitis B virus (HBV) infections are endemic in Korea. The aims of this study were to determine the prevalence of HBsAg positivity in Korea and to evaluate the changes in intrafamilial transmission after introduction of HBV vaccination in 1983. This study was based on the 2001 Korea National Health and Nutrition Examination Survey. A total of 2512 study subjects, aged 10-29 years, were selected from across Korea using a stratified multi-stage probability sampling design. To identify the changes in intrafamilial transmission after the introduction of the HBV vaccination programme, 1850 subjects with parental serological markers were selected. These subjects were then grouped into two birth cohorts (cohort 1: born before 1983; cohort 2: born after 1983). Appropriate sampling weights were used for all analyses. The weighted age-specific prevalence of HBsAg was 4.9% in participants in their 20s and 1.9% in adolescents; the combined weighted prevalence was 3.2%. Of subjects with HBsAg positivity in either parent, 17.5% were HBsAg-seropositive. Of subjects with two HBsAg-negative parents, 1.5% were HBsAg-seropositive. The HBsAg positivity rate of offspring with HBsAg-positive mothers was higher than those with HBsAg-positive fathers (27.3% vs. 4.8%, P<0.001). The weighted HBsAg positivity rate of offspring with HBsAg-negative mothers was 2.3% for cohort 1 and 0.4% for cohort 2 (P<0.01), and for those offspring with HBsAg-positive mothers it was also significantly decreased compared to cohorts 1 and 2 (40.2% vs. 16.4%, P<0.01). However, the weighted HBsAg positivity rate of offspring with HBsAg-positive mothers was still high. Our results showed that introduction of HBV vaccination has resulted in a decline in the overall HBsAg positivity rate and a reduction in intrafamilial transmission in Korea, but further preventive measures for maternal intrafamilial transmission are needed.
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Vacunas contra Hepatitis B/administración & dosificación , Virus de la Hepatitis B/inmunología , Hepatitis B/prevención & control , Hepatitis B/transmisión , Adolescente , Adulto , Distribución de Chi-Cuadrado , Niño , Estudios de Cohortes , Femenino , Hepatitis B/epidemiología , Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Corea (Geográfico)/epidemiología , Masculino , Núcleo Familiar , PrevalenciaRESUMEN
Highly Pathogenic Avian Influenza (HPAI) subtype H5N8 outbreaks occurred in poultry farms in South Korea in 2014 resulting in significant damage to the poultry industry. Between 2014 and 2016, the pandemic disease caused significant economic loss and social disruption. To evaluate the risk factors for HPAI infection in broiler duck farms, we conducted a retrospective case-control study on broiler duck farms. Forty-three farms with confirmed laboratories on premises were selected as the case group, and 43 HPAI-negative farms were designated as the control group. Control farms were matched based on farm location and were within a 3-km radius from the case premises. Spatial and environmental factors were characterized by site visit and plotted through a geographic information system (GIS). Univariable and multivariable logistic regression models were developed to assess possible risk factors associated with HPAI broiler duck farm infection. Four final variables were identified as risk factors in a final multivariable logistic model: "Farms with ≥7 flocks" (odds ratio [OR] = 6.99, 95% confidence interval [CI] 1.34-37.04), "Farm owner with ≥15 years of raising poultry career" (OR = 7.91, 95% CI 1.69-37.14), "Presence of any poultry farms located within 500 m of the farm" (OR = 6.30, 95% CI 1.08-36.93) and "Not using a faecal removal service" (OR = 27.78, 95% CI 3.89-198.80). This highlights that the HPAI H5N8 outbreaks in South Korea were associated with farm owner education, number of flocks and facilities and farm biosecurity. Awareness of these factors may help to reduce the spread of HPAI H5N8 across broiler duck farms in Korea during epidemics. Greater understanding of the risk factors for H5N8 may improve farm vulnerability to HPAI and other subtypes and help to establish policies to prevent re-occurrence. These findings are relevant to global prevention recommendations and intervention protocols.
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Brotes de Enfermedades/veterinaria , Patos/virología , Granjas , Subtipo H5N8 del Virus de la Influenza A , Gripe Aviar/epidemiología , Enfermedades de las Aves de Corral/virología , Animales , Estudios de Casos y Controles , Brotes de Enfermedades/prevención & control , Gripe Aviar/etiología , Modelos Logísticos , Enfermedades de las Aves de Corral/epidemiología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Although transarterial chemotherapy is used to retard tumour progression for hepatocellular carcinoma (HCC) patients awaiting orthotopic liver transplantation (OLT), information regarding the acceptable waiting time and appropriate patient selection for the therapy is lacking. AIM: To examine dropout times and determine the best candidates for pre-transplant transarterial therapy in a cohort study. METHODS: In total, 180 consecutive HCC candidates receiving pre-transplant chemo-lipiodolization were included in the study. RESULTS: Overall, 70 (38.9%) patients dropped off the waiting list during the median follow-up of 19 months. According to the Child-Pugh (C-P) classification, the estimated dropout rates at 1 and 2 years were 17.2% and 44.8% for the C-P A group and 33.4% and 81.3% for the C-P B/C group, respectively. C-P B/C patients experienced more frequent dropouts than C-P A patients (P < 0.001). Risk factor analysis identified C-P classification to be the strongest predictor of dropout (P < 0.001). On multivariate analysis, alpha-fetoprotein (AFP) >100 ng/mL, tumour size >3 cm and multiple nodules remained independently predictive of dropout for C-P A group (all P < 0.05). Candidates with none of these factors were found to be at the lowest risk of dropout, with only a 22.5% dropout rate up to 41 months. CONCLUSIONS: This study suggests that Child-Pugh A patients with one nodule <3 cm and AFP < 100 ng/mL may be the best candidates for pre-transplant chemo-lipiodolization, with the lowest dropout rate. However, comparative studies with other therapeutic options are needed to assess the definitive role of transarterial therapy in this setting.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Antibióticos Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Estudios de Cohortes , Progresión de la Enfermedad , Epirrubicina/administración & dosificación , Femenino , Humanos , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Selección de Paciente , Factores de Riesgo , Listas de EsperaRESUMEN
The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous busulfan, cyclophosphamide and etoposide (i.v. Bu/Cy/E) as a conditioning regimen prior to autologous hematopoietic stem cell transplantation in patients with non-Hodgkin's lymphoma (NHL). Sixty-four patients with relapsed/refractory (n=36) or high-risk (n=28) lymphoma were enrolled. The high-dose chemotherapy consisted of i.v. Bu (0.8 mg kg(-1) i.v. q 6 h from day -7 to day -5), Cy (50 mg kg(-1) i.v. on day -3 and day -2) and E (400 mg m(-2) i.v. on day -5 and day -4). The median age was 43 (range 18-65) years, and 39 patients were male. Diffuse large B-cell lymphoma (40.6%) was the most common histological subtype. All evaluable patients achieved an engraftment of neutrophils (median, day 12) and platelets (median, day 13). Hepatic veno-occlusive disease was observed in four patients (three mild, one moderate grade), and two patients (3.1%) died from treatment-related complications. At a median follow-up of 16.4 months, 15 patients (23.4%) exhibited a relapse or progression, while 13 patients (20.3%) had died of disease. The estimated 3-year overall and progression-free survival for all patients was 72.1 and 70.1%, respectively. In conclusion, the conditioning regimen of i.v. Bu/Cy/E was well tolerated and seemed to be effective in patients with aggressive NHL.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/tratamiento farmacológico , Acondicionamiento Pretrasplante , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Dna2 is a multifunctional enzyme in yeast that possesses endonuclease activity well suited to remove RNA-DNA primers of Okazaki fragments, raising the question of whether endonuclease activity is essential for in vivo Dna2 function. Systematic site-directed mutations of amino acid residues in Saccharomyces cerevisiae DNA2 conserved in the central region of many eukaryotic DNA2 homologs allowed us to identify mutant dna2 alleles that were divided into three groups based on the viability of the mutant cells: (i) viable; (ii) inviable only when expression was repressed; (iii) inviable. Biochemical analyses of recombinant mutant Dna2 proteins isolated from the latter two groups revealed that they possessed normal ATPase/helicase activity, but were impaired in their endonuclease activity. Cells expressing mutant Dna2 enzymes partially impaired in endonuclease activity were viable, but were unable to grow when expression of their mutant Dna2 enzymes was further reduced. Their growth was restored when the mutant Dna2 proteins decreased in nuclease activity were induced to overexpress. In contrast, mutant Dna2 proteins lacking endonuclease activity did not allow cells to grow under any conditions tested. These in vivo and in vitro results demonstrate that the endonuclease activity of Dna2 is essential for Okazaki fragment processing.
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Adenosina Trifosfatasas/metabolismo , ADN Helicasas/metabolismo , Endonucleasas/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimología , Adenosina Trifosfatasas/química , Adenosina Trifosfatasas/genética , Alelos , Secuencia de Aminoácidos , Secuencia Conservada , ADN/metabolismo , ADN Helicasas/química , ADN Helicasas/genética , Desoxirribonucleasa BamHI/metabolismo , Desoxirribonucleasa EcoRI/metabolismo , Expresión Génica , Humanos , Cloruro de Magnesio/farmacología , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Plásmidos/genética , Regiones Promotoras Genéticas , Proteínas Recombinantes , Saccharomyces cerevisiae/crecimiento & desarrollo , Homología de Secuencia , Relación Estructura-Actividad , TransfecciónRESUMEN
In order to gain insights into the structural basis of the multifunctional Dna2 enzyme involved in Okazaki fragment processing, we performed biochemical, biophysical and genetic studies to dissect the domain structure of Dna2. Proteolytic digestion of Dna2 using subtilisin produced a 127 kDa polypeptide that lacked the 45 kDa N-terminal region of Dna2. Further digestion generated two subtilisin-resistant core fragments of approximately equal size, 58 and 60 kDa. Surprisingly, digestion resulted in a significant (3- to 8-fold) increase in both ATPase and endonuclease activities compared to the intact enzyme. However, cells with a mutant DNA2 allele lacking the corresponding N-terminal region were severely impaired in growth, being unable to grow at 37 degrees C, indicating that the N-terminal region contains a domain critical for a cellular function(s) of Dna2. Analyses of the hydrodynamic properties of and in vivo complex formation by wild-type and/or mutant Dna2 lacking the N-terminal 45 kDa domain revealed that Dna2 is active as the monomer and thus the defect in the mutant Dna2 protein is not due to its inability to multimerize. In addition, we found that the N-terminal 45 kDa domain interacts physically with a central region located between the two catalytic domains. Our results suggest that the N-terminal 45 kDa domain of Dna2 plays a critical role in regulation of the enzymatic activities of Dna2 by serving as a site for intra- and intermolecular interactions essential for optimal function of Dna2 in Okazaki fragment processing. The possible mode of regulation of Dna2 is discussed based upon our recent finding that replication protein A interacts functionally and physically with Dna2 during Okazaki fragment processing.
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Adenosina Trifosfatasas/metabolismo , ADN Helicasas/metabolismo , Desoxirribonucleasa I/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimología , Adenosina Trifosfatasas/química , Secuencia de Aminoácidos , Animales , Sitios de Unión , Línea Celular , ADN Helicasas/química , Desoxirribonucleasa I/química , Dimerización , Relación Dosis-Respuesta a Droga , Endodesoxirribonucleasas/genética , Activación Enzimática/efectos de los fármacos , Endonucleasas de ADN Solapado , Regulación Fúngica de la Expresión Génica , Datos de Secuencia Molecular , Estructura Molecular , Peso Molecular , Mutación , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Fenotipo , Estructura Terciaria de Proteína , Saccharomyces cerevisiae/crecimiento & desarrollo , Eliminación de Secuencia , Subtilisina/metabolismo , Subtilisina/farmacología , TemperaturaRESUMEN
BACKGROUND: Little is known about the extent to which transplant recipients face psychologic distress with the receipt of a transplanted organ. The purpose of this study was to investigate health-related quality of life (HRQoL) and psychologic distress in 105 adults who had undergone kidney transplantation (KT). METHODS: HRQoL was measured with the use of the Korean version of Medical Outcome Study Short Form 36 version 2, and psychologic distress with the use of the Transplant Effects Questionnaire (TEQ). Clinical and demographic data were collected from questionnaires. The data were collected from August 2014 to November 2014 at 2 medical centers in Korea. RESULTS: Of the 105 patients, 53.3% were male and the overall mean age was 46.99 years. The mean score of each of the TEQ subscales ranged from 2.45 to 4.62. In the subscales of HRQoL, the mean score of physical component summary (PCS) was 50.23, and the mean score of mental component summary (MCS) was 46.19. MCS was negatively correlated with worry (P = .001) and guilt (P = .037) and positively correlated with adherence (P = .006) in the TEQ subscales, whereas there was no significant correlation between PCS and the TEQ subscales. CONCLUSIONS: The study indicates that mental HRQoL is correlated with psychologic distress. Therefore, to increase the HRQoL, continuous attention is needed in kidney transplant recipients who experience psychologic distress and adherence problem. In addition, further empirical studies should be conducted to explain the mechanisms underlying this relationship.
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Trasplante de Riñón/psicología , Calidad de Vida , Estrés Psicológico/etiología , Receptores de Trasplantes/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Encuestas y CuestionariosRESUMEN
In this report, we investigated the phenotypes caused by temperature-sensitive (ts) mutant alleles of dna2(+) of Schizosaccharomyces pombe, a homologue of DNA2 of budding yeast, in an attempt to further define its function in vivo with respect to lagging-strand synthesis during the S-phase of the cell cycle. At the restrictive temperature, dna2 (ts) cells arrested at late S-phase but were unaffected in bulk DNA synthesis. Moreover, they exhibited aberrant mitosis when combined with checkpoint mutations, in keeping with a role for Dna2 in Okazaki fragment maturation. Similarly, spores in which dna2(+) was disrupted duplicated their DNA content during germination and also arrested at late S-phase. Inactivation of dna2(+) led to chromosome fragmentation strikingly similar to that seen when cdc17(+), the DNA ligase I gene, is inactivated. The temperature-dependent lethality of dna2 (ts) mutants was suppressed by overexpression of genes encoding subunits of polymerase delta (cdc1(+) and cdc27(+)), DNA ligase I (cdc17(+)), and Fen-1 (rad2(+)). Each of these gene products plays a role in the elongation or maturation of Okazaki fragments. Moreover, they all interacted with S. pombe Dna2 in a yeast two-hybrid assay, albeit to different extents. On the basis of these results, we conclude that dna2(+) plays a direct role in the Okazaki fragment elongation and maturation. We propose that dna2(+) acts as a central protein to form a complex with other proteins required to coordinate the multienzyme process for Okazaki fragment elongation and maturation.
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Adenosina Trifosfatasas/genética , ADN Helicasas/genética , Proteínas de Unión al ADN , ADN/metabolismo , Endodesoxirribonucleasas , Factores de Intercambio de Guanina Nucleótido , Proteínas de Saccharomyces cerevisiae , Schizosaccharomyces/enzimología , Schizosaccharomyces/genética , Adenosina Trifosfatasas/antagonistas & inhibidores , Adenosina Trifosfatasas/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Cromosomas/genética , ADN Helicasas/antagonistas & inhibidores , ADN Helicasas/metabolismo , ADN Polimerasa I/genética , ADN Polimerasa I/metabolismo , Replicación del ADN/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Dosificación de Gen , Genes Letales , Genes cdc , Pruebas de Mutagenicidad , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Fase S/genética , Saccharomyces cerevisiae/genética , Análisis de Secuencia de ADN , Esporas Fúngicas/genética , Esporas Fúngicas/crecimiento & desarrollo , Temperatura , Técnicas del Sistema de Dos Híbridos , Rayos UltravioletaRESUMEN
Cyclooxygenase-2 (COX-2) has been suggested to be associated with carcinogenesis. In hepatocellular carcinoma (HCC), the expression pattern of COX-2 protein has been well correlated with the differentiation grade, suggesting that abnormal COX-2 expression plays an important role in hepatocarcinogenesis. We investigated the expression pattern and clinical significance of COX-2 in HCC tissues. In addition, we evaluated the efficacy of a selective COX-2 inhibitor, NS-398, in three hepatoma cell lines. Thirty-six HCC tissues, 15 hepatoma cell lines, 1 colorectal cell line (HT-29), and 1 fibroblast cell line (SV80) were included in the study. We evaluated serological tests and histological and radiological evaluations of HCC tissues. Immunohistochemical staining for COX-2 was performed on 36 HCC tissues and 17 cancer cell lines. A cell viability assay for growth inhibition of NS-398 in five cell lines was performed. Immunohistochemically, all six well-differentiated HCCs were positive, whereas 83% (10 of 12) of the poorly differentiated HCCs were negative. There was no significant relationship between the intensity of COX-2 expression and the level of alpha-fetoprotein, tumor size, presence of portal vein thrombosis, tumor capsule and metastasis, Tumor-Node-Metastasis staging, and growth types (P > 0.05). According to the cell viability assay, NS-398 suppressed the growth of all cell lines, independent of the degree of COX-2 expression. The inhibitory effect on each cell line was identified in 10 microM NS-398 and was significantly strong in 100 microM NS-398. All cell lines exhibited apoptosis, which was identified by 4'-6-diamidino-2-phenylindole staining. In conclusion, COX-2 may be a determinant of the differentiation grade of HCC, and the inhibition of COX-2 can induce growth suppression of hepatoma cell lines via induction of apoptosis.
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Antineoplásicos/farmacología , Carcinoma Hepatocelular/enzimología , Inhibidores de la Ciclooxigenasa/farmacología , Isoenzimas/biosíntesis , Neoplasias Hepáticas/enzimología , Nitrobencenos/farmacología , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Sulfonamidas/farmacología , Adulto , Anciano , Apoptosis , Carcinoma Hepatocelular/patología , División Celular/efectos de los fármacos , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Femenino , Humanos , Isoenzimas/antagonistas & inhibidores , Hígado/enzimología , Neoplasias Hepáticas/patología , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Estadificación de Neoplasias , Células Tumorales CultivadasRESUMEN
Recording of visual evoked potentials (VEPs) to pattern reversal is considered to be a reliable diagnostic procedure for examining patients with anterior visual pathway lesions (optic nerves and chiasm). Less consistent results have been reported in studies of more posterior lesions. The VEPs were recorded in 20 patients with occipital lobe lesions. A maximal VEP response (P94) was recorded at the scalp electrodes situated over the involved occipital lobes and contralateral to the hemianoptic visual field defect, indicating a positive correlation of unilateral occipital lobe lesions, homonymous visual field loss, and the VEP abnormality.
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Encefalopatías/fisiopatología , Lóbulo Occipital/fisiopatología , Percepción Visual/fisiología , Adulto , Anciano , Encefalopatías/diagnóstico , Neoplasias Encefálicas/fisiopatología , Infarto Cerebral/fisiopatología , Dominancia Cerebral/fisiología , Electroencefalografía , Potenciales Evocados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Visuales/fisiopatologíaRESUMEN
The visual evoked potential to pattern reversal was recorded in 50 patients with sarcoidosis. Abnormalities of latency and amplitude were found in 15 patients (30%), including all 4 patients with clinically evident brain disease and 4 of 17 patients with overt ocular disease. Twenty-nine patients had no clinical evidence of ocular or neurologic disease, and 7 of them (24%) had abnormalities of the VEP, implying subclinical sarcoid lesions in structures at the base of the brain.
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Potenciales Evocados Visuales , Sarcoidosis/fisiopatología , Adulto , Electrofisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiopatología , Nervio Óptico/fisiopatología , Tiempo de ReacciónRESUMEN
BACKGROUND: Studies have been performed in order to assess a treatment with 131I able to induce a consistent improvement in Graves' hyperthyroidism. EXPERIMENTAL DESIGN: For this purpose, four different protocols based on four different doses of radioiodine have been tested in Graves' disease patients. Patients never submitted previously to antithyroid drug treatment were given 1 mCi/10 gm of the estimated thyroid weight (group I; n = 50). Group II (n = 48) included patients not previously treated with antithyroid drugs and who were given doses of iodine based on a formula taking into account the rate of thyroid iodine uptake, i.e. 131I dose = microCi/gm of the estimated thyroid weight x 100/24 hrs 131I uptake (%). Patients previously submitted to antithyroid drug therapy were treated with radioiodine whose dose was calculated according to the formula reported above, but the dose was increased in order to overcome the possible resistance of this kind of patients to the effect of 131I. One group (group III; n = 24) received the calculated dose plus 1 microCi/gm of the estimated thyroid weight. Finally, group IV (n = 27) received the calculated dose plus 0.25 microCi/gm of the estimated thyroid weight. RESULTS: The analysis of the patients one year later demonstrated that groups I and II presented the higher percent of euthyroid patients (60% and 58%, respectively) followed by group IV (37%) and group III (29.2%). The percent of patients still exhibiting hyperthyroidism was 28% in group I, 26% in group IV, 12.5% in group III and 8.3% in group II. The highest number of hypothyroid patients was present in group III (58.3%) followed by group IV (37%), group II (33.3%) and group I (12%). CONCLUSIONS: The data here presented suggest that protocols I and II based on relatively low doses of radioiodine are rather effective in reducing Graves' hyperthyroidism in patients not submitted previously to antithyroid drug therapy. The most satisfactory therapy seems that utilized in protocol II, that in front of a fair amount of euthyroid patients (58.3%) presents a very low number of subjects still hyperthyroid (8.3%). However, the number of patients who became hypothyroid (33.3%) as a consequence of the therapy was too high. Hopefully, a better design of the protocol will reduce this figure. The high incidence of hyperthyroidism observed in groups III and IV submitted to a therapy with 131I doses consistently higher than those utilized in groups I and II seems to confirm the hypothesis that hyperthyroid subjects submitted to a therapy with antithyroid drugs become rather resistant to a radioiodine treatment.
Asunto(s)
Enfermedad de Graves/radioterapia , Radioisótopos de Yodo/uso terapéutico , Adolescente , Adulto , Antitiroideos/uso terapéutico , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Phlegmonous enteritis is a rare infective inflammatory disease of the intestine, predominantly involving the submucosal layer. It is difficult to diagnose and often fatal. Its association with alcoholism and various liver diseases, although rarely reported, is well documented. We report a case of phlegmonous enteritis in a male patient with congestive heart failure and colon cancer, and describe the ultrasonographic and CT findings.
Asunto(s)
Neoplasias del Colon/complicaciones , Enteritis/diagnóstico por imagen , Insuficiencia Cardíaca/complicaciones , Anciano , Enteritis/complicaciones , Humanos , Masculino , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
To compare the specific information provided by ultrasound (US) and galactography and to appreciate the clinical applicability of US as a primary diagnostic method for breast tumors associated with nipple discharge, a comparative study of each method in 15 patients with ductal tumors of the breast was performed. To evaluate the smallest anatomical unit of the lactiferous system demonstrable by US, 30 patients with normal lactating breasts were examined prospectively. The smallest anatomical ductal unit that could be evaluated with US in the normal lactating breast was the terminal duct lobular unit (TDLU). US is superior to galactography in detecting masses smaller than 0.5 cm or lesions involving multiple ducts. Galactography is better for visualizing the duct system and detecting calcification. In conclusion, US serves as a primary noninvasive diagnostic tool in patients with clinically suspicious breast tumor associated with bloody nipple discharge, but galactography also should be done in specific circumstances.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Mamografía/métodos , Pezones/metabolismo , Adulto , Femenino , Humanos , Mamografía/instrumentación , Persona de Mediana Edad , UltrasonografíaRESUMEN
During time-critical brain surgery, the detection of developing cerebral ischemia is particularly important because early therapeutic intervention may reduce the mortality of the patient. The purpose of this system is to provide an efficient means of remote teleconsultation for the early detection of ischemia, particularly when subspecialists are unavailable. The hardware and software design architecture for the multimedia brain function teleconsultation system including the dedicated brain function monitoring system is described. In order to comprehensively support remote teleconsultation, multi-media resources needed for ischemia interpretation were included: EEG signals, CSA, CD-CSA, radiological images, surgical microscope video images and video conferencing. PC-based system integration with standard interfaces and the operability over the Ethernet meet the cost-effectiveness while the modular software was customized with a diverse range of data manipulations and control functions necessary for shared workspace and standard interfaces.