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1.
Pharmazie ; 75(4): 154-158, 2020 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-32295693

RESUMEN

Long-term azacitidine (AZA) treatment is necessary for its maximal therapeutic effect. This study examined the continuity and efficacy of AZA treatment in real-world use. We conducted a retrospective study in 38 patients who had completed AZA treatment at the Ogaki Municipal Hospital between April 2011 and August 2019. The median number of AZA received cycles was 4. The number of AZA treatment cycles received was 1-3 cycles in 15 (39.5%), 4-6 cycles in 15 (39.5%), and ≥ 7 cycles in 8 (21.1%). The most common reason for discontinued AZA treatment was infection. Overall response rate was 33.3% in patients with discontinued AZA use (< 4 cycles) and 56.5% in patients with continued AZA (≥ 4). Median overall survival (OS) was 124 (15-529) days and 391 (132-2,825) days in the respective groups (p<0.01). The presence of peripheral blood blasts (PBs) was a prognostic factor for continuation of treatment (p =0.03). Discontinued AZA treatment due to infection (p <0.01), and PBs (p =0.03) were unfavourable prognostic factors for OS. Long-term AZA use is beneficial for improvement and survival. Infection control and presence of PBs were important factors for continuing AZA. These data support the idea of long-term continued treatment with AZA for optimal benefit to patients.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Continuidad de la Atención al Paciente/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Azacitidina/administración & dosificación , Azacitidina/efectos adversos , Femenino , Humanos , Infecciones/complicaciones , Infecciones/epidemiología , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
2.
Eur J Vasc Endovasc Surg ; 52(2): 218-24, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27357968

RESUMEN

OBJECTIVES: Patients with critical limb ischemia (CLI) have poor overall and limb prognosis. Although nutritional status influences overall prognosis, and the Geriatric Nutritional Risk Index (GNRI) is a widely used, simple and well established nutritional status screening method, the association between the GNRI and the overall and limb prognosis of patients with CLI following endovascular therapy (EVT) has not been explored. METHODS: Clinical outcomes were retrospectively evaluated in 473 consecutive patients (74 ± 10 years; 59% male) with CLI who underwent EVT. The GNRI on admission was calculated as follows: [14.89 × albumin (g/dL)] + [41.7 × (body weight/ideal body weight)]. Cox proportional hazard analysis was performed to explore the independent association between the GNRI and mortality and major amputation. RESULTS: Patients (53% ambulatory, 38% wheelchair bound, and 9% bedridden) were divided into two groups based on the median GNRI: the higher group (GNRI ≥ 91.2, n = 237) and the lower group (GNRI < 91.2, n = 236). Median follow up duration after EVT was 11.3 months. Three years after EVT, the survival rate (74% in the higher GNRI, and 48% in the lower GNRI, respectively), and limb salvage rate (92% in the higher GNRI, and 84% in the lower GNRI) were significantly lower in the lower GNRI group. GNRI (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.05), along with being wheelchair bound (HR, 1.87; 95% CI 1.17-2.97; vs. ambulatory status), being bedridden (HR, 3.10; 95% CI, 1.63-2.97; vs. ambulatory status), being on hemodialysis (HR, 2.33; 95% CI, 1.49-3.64), and having chronic heart failure (HR, 2.22; 95% CI, 1.44-3.43) were the independent predictors of mortality. The GNRI (HR, 1.04; 95% CI, 1.01-1.07), being bedridden (HR, 4.15; 95% CI, 1.67-10.3; vs. ambulatory status), isolated below knee disease (HR, 2.49; 95% CI, 1.30-4.77), and hemodialysis (HR, 2.44; 95% CI, 1.23-4.85) were independently associated with major amputation. CONCLUSIONS: The GNRI on admission was independently associated with mortality and major amputation after EVT in patients with CLI.


Asunto(s)
Procedimientos Endovasculares/efectos adversos , Extremidades/irrigación sanguínea , Evaluación Geriátrica , Isquemia/diagnóstico , Evaluación Nutricional , Anciano , Amputación Quirúrgica/estadística & datos numéricos , Femenino , Humanos , Isquemia/complicaciones , Isquemia/mortalidad , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo
3.
J Viral Hepat ; 22(2): 94-102, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24750410

RESUMEN

The short-term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P < 0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 ± 0.9 log copies per mL in overall patients, 2.1 ± 0.8 in survived patients and 1.2 ± 0.9 in dead/transplanted patients. The decline of HBV DNA was significant between the first 2 weeks (P = 0.03) and 4 weeks (P = 0.02) in survived patients, but not in dead/transplanted patients. Our study shows that corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.


Asunto(s)
Corticoesteroides/uso terapéutico , Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/tratamiento farmacológico , Nucleósidos/uso terapéutico , Carga Viral , Adulto , Anciano , ADN Viral/sangre , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
4.
J Viral Hepat ; 22(10): 817-27, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25720442

RESUMEN

Effective recognition of viral infection and successive activation of antiviral innate immune responses are vital for host antiviral defence, which largely depends on multiple regulators, including Toll-like receptors (TLRs) and microRNAs. Several early reports suggest that specific TLR-mediated immune responses can control hepatitis B virus (HBV) replication and express differentially with disease outcome. Considering the versatile function of miR-155 in the TLR-mediated innate immune response, we aimed to study the association between miR-155 and TLRs and their subsequent impact on HBV replication using both a HBV-replicating stable cell line (HepG2.2.15) and HBV-infected liver biopsy and serum samples. Our results showed that miR-155 was suppressed during HBV infection and a subsequent positive correlation of miR-155 with TLR7 activation was noted. Further, ectopic expression of miR-155 in vitro reduced HBV load as evidenced from reduced viral DNA, mRNA and subsequently reduced level of secreted viral antigens (HBsAg and HBeAg). Our results further suggested that CCAAT/enhancer-binding protein-ß (C/EBP-ß), a positive regulator of HBV transcription, was inhibited by miR-155. Taken together, our study established a correlation between miR-155 and TLR7 during HBV infection and also demonstrated in vitro that increased miR-155 level could help to reduce HBV viral load by targeting C/EBP-ß.


Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Virus de la Hepatitis B/inmunología , Hepatocitos/inmunología , Hepatocitos/virología , Hígado/virología , MicroARNs/biosíntesis , Receptor Toll-Like 7/biosíntesis , Línea Celular , Virus de la Hepatitis B/fisiología , Humanos , Hígado/patología , Replicación Viral
5.
Nat Genet ; 12(1): 65-71, 1996 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8528254

RESUMEN

The amplification and overexpression of a number of oncogenes is strongly associated with the progression of a variety of different cancers. We now present a strategy to purify amplified DNA on double minute chromosomes (DMs) to enable analysis of their prevalence and contribution to tumourigenesis. Using cell lines derived from four different tumour types, we have developed a general and rapid method to purify micronuclei that are known to entrap extrachromosomal elements. The isolated DNA is highly enriched in DM sequences and can be used to prepare probes to localize the progenitor single copy chromosomal regions. The capture of DMs by micronuclei appears to be dependent on their lack of a centromere rather than their small size.


Asunto(s)
Aberraciones Cromosómicas , Sondas de ADN , Amplificación de Genes , Micronúcleos con Defecto Cromosómico/ultraestructura , Fraccionamiento Celular/métodos , Centrómero/ultraestructura , Inhibidores Enzimáticos/farmacología , Humanos , Hidroxiurea/farmacología , Hibridación Fluorescente in Situ , Ribonucleótido Reductasas/antagonistas & inhibidores , Células Tumorales Cultivadas
6.
Int J Oral Maxillofac Surg ; 52(10): 1035-1038, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36804052

RESUMEN

Odontogenic fibroma is a rare benign mesenchymal odontogenic tumor, with its histological diversity possibly posing diagnostic challenges. A case of the amyloid variant of central odontogenic fibroma, with epithelial cells in perineural and intraneural locations, is reported herein. The 46-year-old female patient had experienced discomfort related to her anterior right hard palate for approximately 25 years. Clinical examination revealed a depression in the anterior hard palate, and radiographic examination showed a well-defined radiolucent lesion with root resorption of the adjacent teeth. Histologically, the well-circumscribed tumor was composed of hypocellular collagenous connective tissue with small islands of odontogenic epithelium. In addition, the juxta-epithelial deposition of amyloid globules without calcification and epithelial cells in perineural and intraneural locations were observed, which posed a diagnostic challenge in differentiating the lesion from the non-calcifying variant of calcifying epithelial odontogenic tumor and sclerosing odontogenic carcinoma. However, on the basis of the clinical and radiographic findings, which were suggestive of a benign and slowly progressive process given the corticated, unilocular radiolucency, the considerable root resorption, and the long history of this finding in an otherwise healthy patient, the final diagnosis was amyloid variant of central odontogenic fibroma. Increased recognition of this variant of odontogenic fibroma and its differentiation from other more aggressive lesions could help the clinician to avoid overdiagnosis and overtreatment.


Asunto(s)
Fibroma , Tumores Odontogénicos , Resorción Radicular , Neoplasias Cutáneas , Humanos , Femenino , Persona de Mediana Edad , Resorción Radicular/patología , Fibroma/diagnóstico por imagen , Fibroma/cirugía , Fibroma/patología , Tumores Odontogénicos/diagnóstico por imagen , Tumores Odontogénicos/cirugía , Células Epiteliales/patología , Neoplasias Cutáneas/patología
7.
J Viral Hepat ; 19(2): e97-104, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22239532

RESUMEN

There is no study that follows up longitudinal changes in laboratory data of patients with C-viral chronic liver disease (C-CLD) who achieved sustained virological esponse (SVR) with interferon treatment in a long-term study. We investigated the laboratory data in a long-term retrospective cohort study of 581 patients with C-CLD who underwent liver biopsy between January 1986 and December 2005. 467 were treated with interferon and 207 of these patients achieved SVR with follow-up periods of 8.36 ± 5.13 years. Alanine aminotransferase (ALT) levels, albumin levels, platelet counts, and the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values were serially examined during the follow-up period. None of the 207 patients with SVR exhibited hepatitis C virus (HCV) RNA positivity more than 6 months after the end of IFN treatment. Platelet counts and albumin levels increased only in those with eradication of HCV. APRI values decreased more in patients with SVR than in those with nonsustained virological responses (non-SVR). Patients who achieved SVR and had fibrosis stage 0-1 and 2-4 at enrolment had platelet counts that longitudinally increased by 2.81 ± 3.95 and 5.49 ± 4.53 × 10(3) /µL during the 10-year follow-up period, respectively. Albumin levels continuously increased during the first 2 years by 0.15 ± 0.31 and 0.33 ± 0.37 in fibrosis stage 0-1 and 2-4, respectively and then plateaued. ALT levels decreased rapidly one year after the start of treatment by 110.3 ± 140.0 and 100.5 ± 123.4 in fibrosis 0-1 and 2-4, respectively. HCV RNA negativity persisted in all patients with SVR, and laboratory data including APRI longitudinally improved during the long-term follow-up period.


Asunto(s)
Antivirales/administración & dosificación , Análisis Químico de la Sangre , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Carga Viral , Adulto , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biopsia , Estudios de Cohortes , Femenino , Hepatitis C Crónica/virología , Humanos , Interferones/administración & dosificación , Cirrosis Hepática/patología , Pruebas de Función Hepática , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Retrospectivos , Albúmina Sérica/análisis , Índice de Severidad de la Enfermedad
9.
Diabetologia ; 54(6): 1517-26, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21409414

RESUMEN

AIMS/HYPOTHESIS: The breakdown of the blood-nerve barrier (BNB) is considered to be a key step in diabetic neuropathy. Although basement membrane hypertrophy and breakdown of the BNB are characteristic features of diabetic neuropathy, the underlying pathogenesis remains unclear. The purpose of the present study was to identify the possible mechanisms responsible for inducing the hypertrophy of basement membrane and the disruption of the BNB after exposure to AGEs. METHODS: The newly established human peripheral nerve microvascular endothelial cell (PnMEC) and pericyte cell lines were used to elucidate which cell types constituting the BNB regulate the basement membrane and to investigate the effect of AGEs on the basement membrane of the BNB using western blot analysis. RESULTS: Fibronectin, collagen type IV and tissue inhibitor of metalloproteinase (TIMP-1) protein were produced mainly by peripheral nerve pericytes, indicating that the basement membrane of the BNB is regulated mainly by these cells. AGEs reduced the production of claudin-5 in PnMECs by increasing autocrine signalling through vascular endothelial growth factor (VEGF) secreted by the PnMECs themselves. Furthermore, AGEs increased the amount of fibronectin, collagen type IV and TIMP-1 in pericytes through a similar upregulation of autocrine VEGF and transforming growth factor (TGF)-ß released by pericytes. CONCLUSIONS/INTERPRETATION: These results indicate that pericytes may be the main regulators of the basement membrane at the BNB. AGEs induce basement membrane hypertrophy and disrupt the BNB by increasing autocrine VEGF and TGF-ß signalling by pericytes under diabetic conditions.


Asunto(s)
Membrana Basal/patología , Barrera Hematonerviosa/efectos de los fármacos , Productos Finales de Glicación Avanzada/farmacología , Microvasos/patología , Pericitos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Membrana Basal/efectos de los fármacos , Barrera Hematonerviosa/fisiopatología , Células Cultivadas , Claudina-5 , Colágeno Tipo IV/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Endotelio Vascular/patología , Fibronectinas/metabolismo , Humanos , Hipertrofia , Proteínas de la Membrana/metabolismo , Pericitos/efectos de los fármacos , Pericitos/patología , Inhibidor Tisular de Metaloproteinasa-1/metabolismo
10.
J Viral Hepat ; 18(10): e508-15, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21914070

RESUMEN

Quantitative serology for hepatitis B surface antigen (HBsAg) is a new candidate marker for prediction of clinical outcome. The aim of this study was to investigate the clinical significance of quantifying HBsAg in patients with hepatitis B virus (HBV) infection. A total of 424 patients who tested positive for HBsAg and were referred to Chiba University Hospital between January 1985 and April 2008 were included in the study, and the following characteristics were analyzed: age, gender, status of hepatitis B e antigen (HBeAg), alanine aminotransferase level (ALT), HBV DNA level, number of platelets and development of hepatocellular carcinoma. Measurement of HBsAg was performed using the chemiluminescent enzyme immunoassay method. The study group consisted of 239 men and 185 women, and their average age was 40.6 ± 14.0 years. HBsAg showed a positive correlation with HBV DNA level (Pearson's product moment correlation, r = 0.586, P < 0.001) and a weak inverse correlation with age (r = 0.3325, P < 0.001). A control study, matched with age and sex, was performed between two groups with and without HBeAg seroconversion during follow-up period. Compared with the age and sex-matched controls, the change in HBsAg levels per year showed a significant decrease 2 years before seroconversion (paired t-test, P < 0.05). The serial measurement of quantitative HBsAg level has the possibility of predicting the occurrence of HBeAg seroconversion.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/patología , Suero/química , Adulto , Biomarcadores/sangre , ADN Viral/sangre , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento
11.
J Viral Hepat ; 18(7): e292-7, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21129130

RESUMEN

Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.


Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Anciano , Quimioterapia Combinada , Femenino , Genotipo , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/genética , Humanos , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Pronóstico , ARN Mensajero/sangre , ARN Viral/sangre , ARN Viral/genética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Ribavirina/administración & dosificación , Resultado del Tratamiento
12.
Rev Sci Instrum ; 92(11): 114709, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34852526

RESUMEN

We present the architecture of the versatile nuclear magnetic resonance (NMR) spectrometer with software-defined radio technology and its application to the dynamically controlled pulsed magnetic fields. The pulse-field technology is the only solution to access magnetic fields greater than 50 T, but the NMR experiment in the pulsed magnetic field was difficult because of the continuously changing field strength. The dynamically controlled field pulse allows us to perform NMR experiment in a quasi-steady field condition by creating a constant magnetic field for a short time around the peak of the field pulse. We confirmed the reproducibility of the field pulses using the NMR spectroscopy as a high precision magnetometer. With the highly reproducible field strength, we succeeded in measuring the nuclear spin-lattice relaxation rate 1/T1, which had never been measured by the pulse-field NMR experiment without dynamic field control. We also implement the NMR spectrum measurement with both the frequency-sweep and field-sweep modes and discuss the appropriate choices of these modes depending on the magnetic properties of the sample to be measured. This development, with further improvement at a long-duration field pulse, will innovate the microscopic measurement in extremely high magnetic fields.

13.
Nat Commun ; 12(1): 7070, 2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34862386

RESUMEN

The metal-insulator transition (MIT), a fascinating phenomenon occurring in some strongly correlated materials, is of central interest in modern condensed-matter physics. Controlling the MIT by external stimuli is a key technological goal for applications in future electronic devices. However, the standard control by means of the field effect, which works extremely well for semiconductor transistors, faces severe difficulties when applied to the MIT. Hence, a radically different approach is needed. Here, we report an MIT induced by resonant tunneling (RT) in double quantum well (QW) structures of strongly correlated oxides. In our structures, two layers of the strongly correlated conductive oxide SrVO3 (SVO) sandwich a barrier layer of the band insulator SrTiO3. The top QW is a marginal Mott-insulating SVO layer, while the bottom QW is a metallic SVO layer. Angle-resolved photoemission spectroscopy experiments reveal that the top QW layer becomes metallized when the thickness of the tunneling barrier layer is reduced. An analysis based on band structure calculations indicates that RT between the quantized states of the double QW induces the MIT. Our work opens avenues for realizing the Mott-transistor based on the wave-function engineering of strongly correlated electrons.

14.
J Viral Hepat ; 17(9): 618-23, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19889140

RESUMEN

Hepatitis A virus (HAV) infection is still an important issue worldwide. A distinct set of viruses encode proteins that enhance viral cap-independent translation initiation driven by an internal ribosome entry site (IRES) and suppress cap-dependent host translation. Unlike cytolytic picornaviruses, replication of HAV does not cause host cell shut off, and it has been questioned whether HAV proteins interfere with its own and/or host translation. HAV proteins were coexpressed in Huh-7 cells with reporter genes whose translation was initiated by either cap-dependent or cap-independent mechanisms. Among the proteins tested, HAV proteinase 3C suppressed viral IRES-dependent translation. Furthermore, 3C cleaved the polypyrimidine tract-binding protein (PTB) whose interaction with the HAV IRES had been demonstrated previously. The combined results suggest that 3C-mediated cleavage of PTB might be involved in down-regulation of viral translation to give way to subsequent viral genome replication.


Asunto(s)
Cisteína Endopeptidasas/metabolismo , Virus de la Hepatitis A/fisiología , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Biosíntesis de Proteínas , Proteínas Virales/metabolismo , Replicación Viral , Proteasas Virales 3C , Línea Celular , Genes Reporteros , Hepatocitos/virología , Humanos
15.
Sci Rep ; 10(1): 11918, 2020 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-32681110

RESUMEN

Several studies have shown that the human gaze, but not the robot gaze, has significant effects on infant social cognition and facilitate social engagement. The present study investigates early understanding of the referential nature of gaze by comparing-through the eye-tracking technique-infants' response to human and robot's gaze. Data were acquired on thirty-two 17-month-old infants, watching four video clips, where either a human or a humanoid robot performed an action on a target. The agent's gaze was either turned to the target (congruent) or opposite to it (incongruent). The results generally showed that, independent of the agent, the infants attended longer at the face area compared to the hand and target. Additionally, the effect of referential gaze on infants' attention to the target was greater when infants watched the human compared to the robot's action. These results suggest the presence, in infants, of two distinct levels of gaze-following mechanisms: one recognizing the other as a potential interactive partner, the second recognizing partner's agency. In this study, infants recognized the robot as a potential interactive partner, whereas ascribed agency more readily to the human, thus suggesting that the process of generalizability of gazing behaviour to non-humans is not immediate.


Asunto(s)
Tecnología de Seguimiento Ocular , Fijación Ocular/fisiología , Robótica , Femenino , Humanos , Lactante , Estadística como Asunto , Factores de Tiempo
16.
Ann Oncol ; 20(2): 337-42, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18725393

RESUMEN

BACKGROUND: Intestinal mucosal barrier injury (MBI), resulting from myeloablative conditioning for haematopoietic stem-cell transplantation (HSCT), is an important cause of morbidity. Despite its frequency, recognition presents a challenge, while the aetiology needs still to be unravelled. The relationship between enterocyte mass and enterocyte loss was explored by examining citrulline serum levels and by assessing circulating intestinal fatty acid-binding protein (I-FABP) and ileal bile acid-binding protein (I-BABP), proteins released by dying mature enterocytes. PATIENTS AND METHODS: Thirty-four adult patients with haematological malignancy received allogeneic HSCT (HSCT day 0) 12 days after being given idarubicin, cyclophosphamide and total body irradiation as myeloablative conditioning, a regimen known to induce oral and intestinal MBI. Serum levels of citrulline, I-FABP and I-BABP were measured on HSCT days -12, -6, 0, +7, +14 and +21. RESULTS: Myeloablative conditioning resulted in a significant decrease in serum citrulline with the nadir on HSCT day +7; thereafter, levels rose gradually. Simultaneously, a significant decrease in I-FABP and I-BABP levels occurred from the day of transplant until day +14. CONCLUSIONS: Simultaneous reduction and subsequent increase of citrulline and I-FABP and I-BABP levels following cytotoxic treatment show that enterocyte mass corresponds to lower rate of dying enterocytes, indicating reduced turnover of enterocytes. Assessment of enterocyte turnover and mass offers opportunities for evaluation of new MBI therapies.


Asunto(s)
Enterocitos/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Mucosa Intestinal/patología , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Proteínas Portadoras/sangre , Citrulina/sangre , Estudios de Cohortes , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ensayo de Inmunoadsorción Enzimática , Proteínas de Unión a Ácidos Grasos/sangre , Proteínas de Unión a Ácidos Grasos/química , Femenino , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/terapia , Humanos , Idarrubicina/administración & dosificación , Idarrubicina/efectos adversos , Mucosa Intestinal/efectos de los fármacos , Estudios Longitudinales , Masculino , Glicoproteínas de Membrana/sangre , Persona de Mediana Edad , Peso Molecular , Mucositis/tratamiento farmacológico , Mucositis/patología , Estándares de Referencia , Factores de Tiempo , Irradiación Corporal Total/efectos adversos
17.
J Cell Biol ; 126(1): 235-46, 1994 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8027181

RESUMEN

Since a number of anti-glycosphingolipid (GSL) antibody activities have been demonstrated in patients with various neurological disorders, the presence of common antigens between brain microvascular endothelial cells (BMECs) and the nervous tissues presents a potential mechanism for the penetration of macromolecules from the circulation to the nervous system parenchyma. We first investigated GSL composition of cultured bovine BMECs. Bovine BMECs express GM3(NeuAc) and GM3(NeuGc) as the major gangliosides, and GM1, GD1a, GD1b, GT1b, as well as sialyl paragloboside and sialyl lactosaminylparagloboside as the minor species. Sulfoglucuronosyl paragloboside was also found to be a component of the BMEC acidic GSL fraction, but its concentration was lower in older cultures. On the other hand, the amounts of neutral GSLs were extremely low, consisting primarily of glucosylceramide. In addition, we analyzed the effect of anti-SGPG IgM antibody obtained from a patient of demyelinative polyneuropathy with macroglobulinemia against cultured BMECs. Permeability studies utilizing cocultured BMEC monolayers and rat astrocytes revealed that the antibody facilitated the leakage of [carboxy-14C]-inulin and 125I-labeled human IgM through BMEC monolayers. A direct cytotoxicity of this antibody against BMECs was also shown by a leakage study using [51Cr]-incorporated BMECs. This cytotoxicity depended on the concentration of the IgM antibody, and was almost completely blocked by preincubation with the pure antigen, sulfoglucuronosyl paragloboside. Our present study strongly supports the concept that immunological insults against BMECs induce the destruction or malfunction of the blood-nerve barrier, resulting in the penetration of the immunoglobulin molecule to attach peripheral nerve parenchyma.


Asunto(s)
Encéfalo/irrigación sanguínea , Enfermedades Desmielinizantes/inmunología , Endotelio Vascular/inmunología , Globósidos/inmunología , Glicoesfingolípidos/inmunología , Inmunoglobulina M/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Astrocitos , Encéfalo/inmunología , Encéfalo/patología , Bovinos , Permeabilidad de la Membrana Celular , Células Cultivadas , Radioisótopos de Cromo , Citotoxicidad Inmunológica , Enfermedades Desmielinizantes/etiología , Gangliósido G(M3)/inmunología , Gangliósido G(M3)/aislamiento & purificación , Glicoesfingolípidos/aislamiento & purificación , Inulina/farmacocinética , Ratas
18.
Maturitas ; 62(1): 53-7, 2009 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-19042101

RESUMEN

OBJECTIVES: Hormone replacement therapy (HRT) increases skin elasticity in postmenopausal women. However, the effects of raloxifene, a selective estrogen receptor modulator (SERM), on skin degenerative changes in postmenopausal women remain unknown. We investigated whether raloxifene increases skin elasticity, similar to HRT, in postmenopausal women. METHODS: In a 12-month trial, 17 postmenopausal women (mean age, 66.4+/-7.8 years) received continuous raloxifene treatment (60 mg/day), 19 women (56.2+/-6.4 years) received continuous 17-beta estradiol treatment using a patch (0.72 mg/2 days) plus cyclic medroxyprogesterone acetate (2.5mg/day, for 12 days/month), and 11 women (58.1+/-7.3 years) did not receive either therapy. In each subject, the skin elasticity of the forearm was measured using a suction device at baseline and at 12 months after the start of the study. RESULTS: Raloxifene and HRT significantly increased skin elasticity from 52.4+/-3.8% and 64.1+/-7.2% at baseline to 55.1+/-4.7% and 67.4+/-7.4% after 12 months, respectively (P<0.05, each), but the untreated subjects did not exhibit any significant change in skin elasticity during the study. The delta value for skin elasticity was significantly higher among the raloxifene and HRT subjects than among the untreated subjects (P<0.05, each). CONCLUSIONS: These findings suggest that raloxifene may have a beneficial effect on skin elasticity, which undergoes degenerative changes in postmenopausal women, in addition to its effects on bone metabolism.


Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Elasticidad/efectos de los fármacos , Terapia de Reemplazo de Estrógeno , Clorhidrato de Raloxifeno/farmacología , Piel/efectos de los fármacos , Anciano , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Estudios de Casos y Controles , Estradiol/farmacología , Femenino , Sofocos/tratamiento farmacológico , Humanos , Acetato de Medroxiprogesterona/farmacología , Persona de Mediana Edad , Posmenopausia
19.
Dis Esophagus ; 22(4): E6-E10, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19473209

RESUMEN

Esophageal schwannoma is rare and it is difficult preoperatively to confirm a definitive diagnosis, even using current imaging techniques. We present a case of a benign esophageal schwannoma that was surgically excised and confirmed by immunohistochemical staining. Conventional radiological studies, including barium meal, computed tomography and endoscopic examination had shown a solid submucosal tumor of the upper thoracic esophagus but had been unable to confirm the diagnosis. Positron emission tomography was carried out to evaluate the malignant potential and showed a high uptake of 18F-fluorodeoxyglucose (FDG) into the tumor in both the early and delayed phase, suggesting that the tumor was a potentially malignant tumor such as a gastrointestinal stromal tumor. This is the first reported case of esophageal schwannoma that indicated a high FDG uptake. Although consensus has not been reached regarding the precise mechanism of FDG accumulation in schwannomas, we discuss our clinicopathological findings and review other studies of the subject.


Asunto(s)
Neoplasias Esofágicas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neurilemoma/diagnóstico por imagen , Neurilemoma/cirugía , Tomografía de Emisión de Positrones/métodos , Anciano , Anastomosis Quirúrgica , Biopsia con Aguja , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagectomía , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Estadificación de Neoplasias , Neurilemoma/patología , Medición de Riesgo , Sensibilidad y Especificidad , Toracotomía , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
20.
J Comp Pathol ; 171: 53-58, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31540625

RESUMEN

Mycoplasma bovis is a microorganism associated with pneumonia, mastitis, arthritis and otitis media of cattle; however, there are no reports of this organism causing bovine endocarditis. Five adult cattle with endocarditis characterized by caseated lesions (diameter 5-12 cm) of the endocardial surface of the left atrium, but without lesions in heart valves or affecting the right side of the heart, were identified in slaughterhouses in Japan. M. bovis was successfully isolated from the lesions and M. bovis antigen was detected immunohistochemically within the lesions. The results suggest that the lesions may have been associated with M. bovis alone. To our knowledge, this is the first demonstration of bovine endocarditis associated with M. bovis.


Asunto(s)
Enfermedades de los Bovinos/microbiología , Endocarditis Bacteriana/veterinaria , Infecciones por Mycoplasma/veterinaria , Mycoplasma bovis/aislamiento & purificación , Animales , Bovinos , Enfermedades de los Bovinos/patología , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/patología , Infecciones por Mycoplasma/microbiología , Infecciones por Mycoplasma/patología
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