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1.
Ultrasound Obstet Gynecol ; 63(4): 446-456, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38197327

RESUMO

OBJECTIVE: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). METHODS: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. RESULTS: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z-score of < -2 in the sagittal (P = 0.003) and three-vessel-and-trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. CONCLUSIONS: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Coartação Aórtica , Canal Arterial , Gravidez , Feminino , Humanos , Coartação Aórtica/diagnóstico por imagem , Ultrassonografia Pré-Natal , Aorta/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Canal Arterial/diagnóstico por imagem , Estudos Retrospectivos
2.
J Hosp Infect ; 146: 151-159, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37516280

RESUMO

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is the most common pathogen in orthopaedic surgical site infections (SSIs). However, few studies have investigated the transmission process of orthopaedic MRSA SSI. AIM: To investigate the transmission process of orthopaedic MRSA SSI using epidemiological and molecular analyses and to determine a method to prevent MRSA SSI in nosocomial orthopaedic surgery. METHODS: Active MRSA surveillance, preoperative decolonization and contact precautions for MRSA-positive cases was performed at our institution. Changes in epidemic strains were evaluated and the possibility of transmission from patients in an orthopaedic ward of a Japanese tertiary-care hospital was assessed by genotyping stored MRSA strains. In addition, data on the prevalence of MRSA SSI, MRSA colonization, and use of an alcohol antiseptic agent (mL/patient-days) during 2005-2022 were retrospectively assessed. FINDINGS: SCCmec type II strain in the SSI group decreased over time, associated with fewer outbreaks. Even during a period of high infection rates, no cases of transmission-induced SSI from nasal MRSA carriers were identified. The infection rate correlated negatively with the use of an alcohol antiseptic agent (r = -0.82; P < 0.0001). Two cases among five nasal carriers developed MRSA SSI caused by strains different from those related to nasal colonization. CONCLUSION: The infection control measures for transmission from the hospital reservoirs including strict adherence to hand hygiene and decolonization of carriers is likely to be important for the prevention of orthopaedic MRSA SSI. However, the need for contact precautions for decolonized nasal carriers might be low.

3.
J Hosp Infect ; 129: 189-197, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35835283

RESUMO

BACKGROUND: Surgical antimicrobial prophylaxis (SAP) is one of the major purposes of antimicrobial use. AIM: To determine the adherence to the Japanese SAP guidelines in Japanese university hospitals. METHODS: This was a retrospective cohort study including 15 general hospitals and one dental university hospital. Up to three cases of 18 designated surgeries were evaluated regarding adherence to Japanese SAP guidelines: selection of antibiotics, timing of administration, re-dosing intervals, and duration of SAP. When all items were appropriate, surgery was defined as 'appropriate'. FINDINGS: In total, 688 cases (22-45 cases per surgery) were included. The overall appropriateness was 46.8% (322/688), and the appropriateness of each surgery ranged from 8.0% (2/25, cardiac implantable electronic device implantation) to 92.1% (35/38, distal gastrectomy). The appropriateness of each item was as follows: pre/intraoperative selections, 78.5% (540/688); timing of administrations, 96.0% (630/656); re-dosing intervals, 91.6% (601/656); postoperative selection, 78.9% (543/688); and duration of SAP, 61.4% (423/688). The overall appropriateness of hospitals ranged from 17.6% (9/51) to 73.3% (33/45). The common reasons for inappropriateness were the longer duration (38.5%, 265/688) and choice of antibiotics with a non-optimal antimicrobial spectrum before/during, and after surgery (19.0%, 131/688 and 16.9%, 116/688, respectively), compared to the guideline. CONCLUSIONS: Adherence to the guidelines differed greatly between the surgeries and hospitals. Large-scale multi-centre surveillance of SAP in Japanese hospitals is necessary to identify inappropriate surgeries, factors related to the appropriateness, and incidences of surgical site infections.


Assuntos
Anti-Infecciosos , Antibioticoprofilaxia , Humanos , Estudos Retrospectivos , Hospitais Universitários , Japão , Fidelidade a Diretrizes , Antibacterianos/uso terapêutico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/tratamento farmacológico , Anti-Infecciosos/uso terapêutico
4.
BJS Open ; 4(5): 804-810, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32700415

RESUMO

BACKGROUND: The role of antithrombotic chemoprophylaxis in prevention of venous thromboembolism (VTE) in laparoscopic surgery for gastric and colorectal malignancies is unknown. This study compared the addition of enoxaparin following intermittent pneumatic compression (IPC) with IPC alone in patients undergoing laparoscopic surgery for gastrointestinal malignancy. METHODS: In this multicentre RCT, eligible patients were older than 40 years and had a WHO performance status of 0 or 1. Exclusion criteria were prescription of antiplatelet or anticoagulant drugs and history of VTE. Patients were allocated to IPC or to ICP with enoxaparin in a 1 : 1 ratio. Stratification factors included sex, location of cancer, age 61 years and over, and institution. Enoxaparin was administered on days 1-7 after surgery. Primary outcome was VTE, evaluated by multidetector CT on day 7. RESULTS: Of 448 patients randomized, 208 in the IPC group and 182 in the IPC with enoxaparin group were evaluated. VTE occurred in ten patients (4·8 per cent) in the IPC group and six (3·3 per cent) in the IPC with enoxaparin group (P = 0·453). Proximal deep vein thrombosis and/or pulmonary embolism occurred in seven patients (3·4 per cent) in the IPC group and one patient (0·5 per cent) in the IPC with enoxaparin group (P = 0·050). All VTE events were asymptomatic and non-fatal. Bleeding occurred in 11 of 202 patients in the IPC with enoxaparin group, and one patient needed a transfusion. All bleeding events were managed by discontinuation of the drug. CONCLUSION: IPC with enoxaparin after laparoscopic surgery for gastric and colorectal malignancies did not reduce the rate of VTE. Registration number: UMIN000011667 ( https://www.umin.ac.jp/).


ANTECEDENTES: El papel de la quimioprofilaxis para la prevención del tromboembolismo venoso (venous thromboembolism, VTE) en la cirugía laparoscópica de los tumores malignos gástricos y colorrectales se desconoce. El objetivo de este estudio fue comparar la quimioprofilaxis antitrombótica (enoxaparina) y la compresión neumática intermitente (intermittent pneumatic compression, IPC) en pacientes sometidos a cirugía laparoscópica de tumores malignos abdominales. MÉTODOS: Se efectuó un ensayo aleatorizado, controlado y multicéntrico de pacientes sometidos a cirugía laparoscópica de tumores gástricos y colorrectales en Japón. Los criterios de inclusión eran pacientes mayores de 40 años de edad y con un estado funcional de WHO de 0-1. Los criterios de exclusión fueron la prescripción al paciente de fármacos antiagregantes o anticoagulantes y la historia de VTE. Los pacientes fueron asignados a IPC y ICP con la adición de enoxaparina en una relación 1:1. Los factores de estratificación incluyeron el sexo, la localización del cáncer, la edad mayor o menor de 61 años, y la institución. La enoxaparina fue administrada en los días postoperatorios (postoperative day, POD) 1-7. El resultado primario fue la VTE evaluada mediante tomografía computarizada multidetector en el POD7. Los cálculos de la potencia determinaron que se requerían 184 pacientes en cada grupo. RESULTADOS: De los 448 pacientes aleatorizados, se evaluaron finalmente 208 pacientes en el grupo IPC y 182 pacientes en el grupo IPC más enoxaparina. La VTE ocurrió en 10 de 208 pacientes en el grupo IPC (4,8%) y 6 de 182 pacientes en el grupo IPC más enoxaparina (3,3%) (P = 0,45). La trombosis venosa profunda proximal (proximal deep vein thrombosis, DVT) y/o el embolismo pulmonar (pulmonary embolism, PE) ocurrieron en 7 de 208 pacientes en el grupo IPC (3,4%) y 1 de 182 pacientes en el grupo IPC más enoxaparina (0,55%) (riesgo relativo 0,163, i.c. del 95% 0,020-1,314, P = 0,0503). Todos los eventos de VTE fueron asintomáticos y no mortales. Se produjo una hemorragia en 11 de 202 pacientes en el grupo IPC con enoxaparina (5,4%, i.c. del 95% 3,1%-9,5%, P < 0,001), y un paciente precisó transfusión. Todos los eventos hemorrágicos pudieron ser tratados con la interrupción del fármaco. CONCLUSIÓN: La IPC con la adición de enoxaparina tras cirugía laparoscópica de los tumores malignos gástricos y colorrectales no disminuye la VTE.


Assuntos
Enoxaparina/uso terapêutico , Dispositivos de Compressão Pneumática Intermitente , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/uso terapêutico , Neoplasias Colorretais/cirurgia , Feminino , Hemorragia/epidemiologia , Hemorragia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/prevenção & controle , Neoplasias Gástricas/cirurgia , Tromboembolia Venosa/epidemiologia
5.
Phys Rev Lett ; 124(4): 047202, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32058748

RESUMO

We have theoretically investigated transport properties of the classical Heisenberg antiferromagnet on the triangular lattice, in which a binding-unbinding topological transition of Z_{2} vortices is predicted to occur at a finite temperature T_{v}. It is shown by means of the hybrid Monte Carlo and spin-dynamics simulations that the longitudinal spin-current conductivity exhibits a divergence at T_{v}, while the thermal conductivity only shows a monotonic temperature dependence with no clear anomaly at T_{v}. The significant enhancement of the spin-current conductivity is found to be due to the rapid growth of the spin-current-relaxation time toward T_{v}, which can be understood as a manifestation of the topological nature of the free Z_{2} vortex whose lifetime gets longer toward T_{v}. The result suggests that the spin-current measurement is a promising probe to detect the Z_{2}-vortex topological transition, which has remained elusive in experiments.

6.
Rev Sci Instrum ; 89(12): 123111, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30599547

RESUMO

Herein, we report an effective method for the generation of radio-frequency (RF) sidebands in an electro-optic modulator for the simultaneous magneto-optical trapping of two isotopes. This is achieved by switching the RF signals alternately, which suppresses the generation of unwanted frequency signals and improves the laser power per sideband. The generated sidebands are successfully applied to a dual-rubidium-isotope magneto-optical trap (MOT), which results in an increased number of trapped atoms. This simple, flexible, and robust technique can be implemented in experiments that require a large number of atoms in multiple-isotope MOTs and for various applications.

7.
Eur J Clin Microbiol Infect Dis ; 35(4): 665-71, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26864040

RESUMO

This study was performed to determine whether multiparous pregnant women are prone to influenza. A questionnaire survey was conducted at 19 centres located throughout Japan, targeting all 6,694 postpartum women within 7 days after birth before leaving the hospital. All women gave birth during the study period between March 1, 2015, and July 31, 2015. Data regarding vaccination and influenza infection in or after October 2014, age, previous experience of childbirth, and number and ages of cohabitants were collected. Seventy-eight percent (n = 51,97) of women given questionnaires responded. Of these, 2,661 (51 %) and 364 (7.0 %) women reported having been vaccinated and having contracted influenza respectively. Multiparous women had a higher risk of influenza regardless of vaccination status (8.9 % [121/1362] vs 5.7 % [74/1299], relative risk [95 % confidence interval], 1.80 [1.36 to 2.38] for vaccinated and 9.3 % [112/1198] vs 4.3 % [57/1328], 2.18 [1.60 to 2.97] for unvaccinated women) compared to primiparous women. The risk of influenza increased with increasing number of cohabitants: 4.8 % (100/2089), 7.5 %, (121/1618), 9.0 %, (71/785), and 10.4 % (58/557) for women with 1, 2, 3, and ≥4 cohabitants respectively. Family size is a risk factor for influenza infection in pregnancy.


Assuntos
Influenza Humana/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Adolescente , Adulto , Povo Asiático , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Japão/epidemiologia , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
8.
Appl Opt ; 55(5): 1164-9, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26906392

RESUMO

We demonstrate frequency offset locking between two laser sources using a waveguide-type electro-optic modulator (EOM) with 10th-order sidebands for magneto-optical trapping of Fr atoms. The frequency locking error signal was successfully obtained by performing delayed self-homodyne detection of the beat signal between the repumping frequency and the 10th-order sideband component of the trapping light. Sweeping the trapping-light and repumping-light frequencies with keeping its frequency difference of 46 GHz was confirmed over 1 GHz by monitoring the Doppler absorption profile of I2. This technique enables us to search for a resonance frequency of magneto-optical trapping of Fr.

10.
Phys Rev Lett ; 113(10): 102501, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25238351

RESUMO

The direct 3α decay branch from the 02+ state at Ex=7.65 MeV in 12C, which is known as the Hoyle state, is considered to affect the triple-α reaction rate strongly and to give crucial information on its structure. We have performed a high-precision measurement of the 3α decay from this state using the 12C(12C,3α)12C reaction at E12C=110 MeV. The branching ratio of the direct 3α decay was under the detection limit in the present experiment. By comparing with Monte Carlo simulations for three decay mechanisms as the sequential decay through the ground state of ^{8}Be, the direct decay with equal energies of three α particles, and the direct decay to the phase space uniformly, we have obtained the upper limit of 0.2% on the direct 3α decay.

11.
Rev Sci Instrum ; 85(2): 02A732, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24593466

RESUMO

The search for the violation of the fundamental symmetry in a radioactive atom is the promising candidate for precision tests of the standard model and its possible extensions. The subtle signal arising from the symmetry violation is enhanced in heavy atoms, such as a francium (Fr). To realize high precision measurements, a large amount of radioactive isotopes is required. The Fr is produced via a nuclear fusion reaction using a melted gold target with a (18)O primary beam at Cyclotron and Radioisotope Center, Tohoku University. The maximum extraction efficiency of the Fr ion was achieved at approximately 35%. The beam line consists of an electrostatic deflector, three electrostatic quadrupole triplets to the measurement area at 10 m away from the reaction point, and several beam diagnosis systems. We optimized parameters of the beam line.

12.
Appl Radiat Isot ; 77: 94-102, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23542121

RESUMO

It is difficult to obtain images of thin slices from measurement of spin-spin relaxation (R2) with magnetic resonance imaging (MRI) using the traditional dose reading method of polymer gel dosimetry. In this study, the dose reading method was performed using X-ray computed tomography (CT) for proton beam measurements in order to enable collection of thin slices. In addition, three-dimensional (3D) images of polymer gels were constructed using volume rendering. As a result of acquisition of thin slices, more detailed 3D data consisting of smaller voxel sizes compared to R2 were acquired. However, it was found that with thin slice thicknesses and small voxels, the signal-to-noise ratio around the voxels deteriorated. In addition, the coefficient of variation of non-irradiated gels with CT was smaller than that with R2 MRI.


Assuntos
Géis/efeitos da radiação , Imageamento por Ressonância Magnética/métodos , Polímeros/efeitos da radiação , Radiometria/métodos , Radioterapia Guiada por Imagem/métodos , Tomografia Computadorizada por Raios X/métodos , Terapia com Prótons , Doses de Radiação
13.
Clin Exp Hypertens ; 35(8): 574-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23488879

RESUMO

The circadian variations in the hemodynamics and locomotor activity (ACT) of congenic rats derived from stroke-prone spontaneously hypertensive (SHRSP) rats and Wistar-Kyoto (WKY) rats have not been studied in detail. We used radio telemetry and the maximum entropy method to examine these variations. The systolic arterial pressure of the congenic rats was intermediate between those of the SHRSP rats and WKY rats, while their heart rate was lower than that of the SHRSP rats. The congenic rats also showed the highest ACT. The circadian variations in the heart rates of the congenic rats were more like those of the WKY rats, and the variations in their ACT were more similar to those of the SHRSP rats.


Assuntos
Pressão Arterial/fisiologia , Ritmo Circadiano/fisiologia , Frequência Cardíaca/fisiologia , Atividade Motora/fisiologia , Animais , Animais Congênicos , Hemodinâmica , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sístole
14.
Cancer Gene Ther ; 19(11): 767-72, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22956040

RESUMO

Replication-selective oncolytic viruses are being developed for human cancer therapy. We previously developed an attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site. OBP-301 can replicate in, and causes selective lysis of, human cancer cells. Valproic acid (VPA), which is an effective antiepileptic drug, is known to inhibit the histone deacetylase activities. We determined whether the antitumor effect of OBP-301 could be enhanced by VPA in human lung cancer cells. In an in vitro cell viability assay, OBP-301 infection killed four human lung cancer cell lines, H1299, H1299-R5 (a subline of H1299 with a low level of the coxsackievirus and adenovirus receptor (CAR) expression), H460, and A549, more efficiently in the presence of VPA than in its absence. VPA treatment increased CAR expression in all the four lung cancer cells. Consistent with their CAR upregulation, the infection efficiency of adenoviruses in the presence of VPA was significantly higher than that in its absence. The molecular mechanism of this combined effect could be explained by an increase in adenovirus infectivity via VPA-mediated upregulation of CAR. These results suggest that treatment with OBP-301 in combination with VPA is a promising strategy for human lung cancer.


Assuntos
Adenoviridae/metabolismo , Antineoplásicos/farmacologia , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/metabolismo , Vírus Oncolíticos/metabolismo , Telomerase/metabolismo , Ácido Valproico/farmacologia , Adenoviridae/genética , Adenoviridae/fisiologia , Proteínas E1A de Adenovirus/genética , Proteínas E1A de Adenovirus/metabolismo , Proteínas E1B de Adenovirus/genética , Proteínas E1B de Adenovirus/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/genética , Enterovirus/genética , Enterovirus/metabolismo , Enterovirus/fisiologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética , Vírus Oncolíticos/fisiologia , Telomerase/genética , Replicação Viral
15.
Oncogene ; 29(8): 1145-54, 2010 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-19935710

RESUMO

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that is related to asbestos exposure. MPM is characterized by rapid and diffuse local growth in the thoracic cavity, and it has a poor prognosis because it is often refractory to conventional therapy. Although MPM is an extraordinarily challenging disease to treat, locoregional virotherapy may be useful against this aggressive disease because of the accessibility by intrapleural virus delivery. In this study, we show that telomerase-specific, replication-selective adenovirus OBP-301 can efficiently infect and kill human mesothelioma cells by viral replication. Intrathoracic administration of virus significantly reduced the number and size of human mesothelioma tumors intrathoracically implanted into nu/nu mice. A high-definition, fluorescence optical imaging system with an ultra-thin, flexible fibered microprobe clearly detected intracellular replication of green fluorescent protein-expressing oncolytic virus in intrathoracically established mesothelioma tumors. As the extracellular matrix (ECM) may contribute to the physiological resistance of a solid tumor by preventing the penetration of therapeutic agents (including oncolytic viruses), we also examined whether the co-expression of heparanase, an endoglucuronidase capable of specifically degrading heparan sulfate, that influences the physiological barrier to macromolecule penetration, can modify the permeability of the ECM, resulting in profound therapeutic efficacy. Co-injection of OBP-301 and a replication-defective adenovirus (Ad-S/hep)-expressing heparanase resulted in more profound antitumor effects without apparent toxicity in an orthotopic pleural dissemination model. Our results suggest that intrathoracic dual virotherapy with telomerase-specific oncolytic adenovirus in combination with heparanase-expressing adenovirus may be efficacious in the prevention and treatment of pleural dissemination of human malignant mesothelioma.


Assuntos
Adenoviridae/genética , Terapia Genética , Glucuronidase/genética , Mesotelioma/terapia , Terapia Viral Oncolítica , Neoplasias Pleurais/terapia , Transfecção/métodos , Adenoviridae/enzimologia , Adenoviridae/crescimento & desenvolvimento , Animais , Linhagem Celular Tumoral , Terapia Combinada , Regulação Neoplásica da Expressão Gênica , Técnicas de Transferência de Genes , Glucuronidase/metabolismo , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/terapia , Mesotelioma/induzido quimicamente , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Pleurais/patologia , Biossíntese de Proteínas , Replicação Viral , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Clin Exp Immunol ; 153(3): 448-55, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18647322

RESUMO

In this study, normal adult mice carried B220(high) conventional B cells in the spleen and liver, but carried both B220(high) and B220(low) in the bone marrow. However, at the neonatal stage, only B220(low) unconventional B cells were found in all these organs. This pattern continued up to 2 weeks after birth, and at this stage autoantibodies were detected in the sera. This phenomenon was seen in all tested young mice (1-2 weeks), irrespective of their gender. Furthermore, at older stages (more than 20 weeks), B220(low) cells reappeared in the spleen and liver, and these B220(low) cells became dominant in the bone marrow. Autoantibodies also reappeared in the sera of these older mice. Cell-sorting experiments revealed that B220(low) cells were able to produce autoantibodies upon lipopolysaccharide stimuli in vitro. These results suggest that B220(low) cells appear at both neonatal and older stages as physiological responses and eventually produce autoantibodies.


Assuntos
Autoanticorpos/imunologia , Linfócitos B/imunologia , Medula Óssea/imunologia , Fígado/imunologia , Baço/imunologia , Animais , Animais Recém-Nascidos , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
Gene Ther ; 15(17): 1233-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18580968

RESUMO

Oncolytic adenoviruses are a promising tool in cancer therapy. In this study, we characterized the role of autophagy in oncolytic adenovirus-induced therapeutic effects. OBP-405, an oncolytic adenovirus regulated by the human telomerase reverse transcriptase promoter (hTERT-Ad, OBP-301) with a tropism modification (RGD) exhibited a strong antitumor effect on glioblastoma cells. When autophagy was inhibited pharmacologically, the cytotoxicity of OBP-405 was attenuated. In addition, autophagy-deficient Atg5(-/-) mouse embryonic fibroblasts (MEFs) were less sensitive than wild-type MEFs to OBP-405. These findings indicate that OBP-405-induced autophagy is a cell killing effect. Moreover, autophagy-inducing therapies (temozolomide and rapamycin) synergistically sensitized tumor cells to OBP-405 by stimulating the autophagic pathway without altering OBP-405 replication. Mice harboring intracranial tumors treated with OBP-405 and temozolomide survived significantly longer than those treated with temozolomide alone, and mice treated with OBP-405 and the rapamycin analog RAD001 survived significantly longer than those treated with RAD001 alone. The observation that autophagy inducers increase OBP-405 antitumor activity suggests a novel strategy for treating patients with glioblastoma.


Assuntos
Autofagia/efeitos dos fármacos , Neoplasias Encefálicas/terapia , Terapia Genética/métodos , Glioblastoma/terapia , Terapia Viral Oncolítica/métodos , Adenoviridae/genética , Animais , Linhagem Celular Tumoral , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Camundongos , Vírus Oncolíticos/genética , Sirolimo/uso terapêutico , Temozolomida
18.
J Neural Transm (Vienna) ; 115(3): 521-30, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18301953

RESUMO

Abnormality in cytokine signaling is implicated in the neuropathology of schizophrenia. Previously, we established an animal model for schizophrenia by administering epidermal growth factor (EGF) to neonatal rats. Here we investigated effects of the anthraquinone derivatives emodin (3-methyl-1,6,8-trihydroxyanthraquinone) and sennoside (bis-[D: -glucopyranosyl-oxy]-tetrahydro-4,4'-dihydroxy-dioxo[bianthracene]-2,2'-dicarboxylic acid) on behaviors of this model and EGF signaling. Subchronic oral administration of emodin (50 mg/kg) suppressed acoustic startle responses and abolished prepulse inhibition (PPI) deficits in this rodent model. ANCOVA revealed that emodin had distinct effects on PPI and startle responses. In contrast, sennoside (50 mg/kg) had no effects. Emodin attenuated weight gain initially during treatment but had no apparent effect on weight gain and locomotor activity thereafter. Application of emodin to neocortical cultures attenuated the phosphorylation of ErbB1 and ErbB2. We conclude that emodin can both attenuate EGF receptor signaling and ameliorate behavioral deficits. Therefore, emodin might be a novel class of a pro-drug for anti-psychotic medication.


Assuntos
Antipsicóticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Emodina/farmacologia , Esquizofrenia/tratamento farmacológico , Animais , Antraquinonas/farmacologia , Western Blotting , Catárticos/farmacologia , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/toxicidade , Inibição Neural/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/efeitos dos fármacos , Esquizofrenia/induzido quimicamente , Extrato de Senna , Senosídeos
19.
Phys Rev Lett ; 99(1): 019701; discussion 019702, 2007 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-17678196
20.
Australas Radiol ; 51(4): 330-3, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17635468

RESUMO

The purpose of this study was to establish quantification method of lactate concentration by proton magnetic resonance spectroscopy (MRS) carried out using a conventional 1.5-T MRI machine. We used a lactate phantom with known concentrations (1, 1.5, 3, 6, 12 and 14 mmol/L). As a clinical example, a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was evaluated. Proton MRS was carried out using a clinical 1.5-T super-conducting magnetic resonance whole-body system. Data were acquired by point resolved spectroscopy. A coupling constant of J = 7.35 Hz (2/J = 272 ms) and two long in-phase echo time of 272 ms and 544 ms were used to calculate the T2 relaxation time. The tissue water signal was used as an internal standard to quantify lactate. The correlation coefficient R between the calculated lactate concentrations and the known concentration of lactate was 0.99 with a constant factor of 0.32 (1/3.14). In patients with MELAS, the lactate concentration measured by MRS was 6.2 mmol/kg wet weight, which is similar to the value obtained in previous studies. In the present study, we have established a reliable method for lactate quantification in a phantom study and have shown a sample of clinical case of MELAS.


Assuntos
Lactatos/análise , Imageamento por Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética/métodos , Adulto , Biomarcadores/análise , Química Encefálica , Feminino , Humanos , Síndrome MELAS/diagnóstico , Imagens de Fantasmas , Prótons , Índice de Gravidade de Doença
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