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1.
Rev Sci Instrum ; 91(2): 023318, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32113411

RESUMEN

To provide a very powerful vanadium (V) beam with an intensity of at least 6 particle µA for synthesizing a new superheavy element (SHE) with atomic number Z = 119, we have developed a high-temperature oven (HTO) system to evaporate the metallic V powder inside the new superconducting (SC) electron cyclotron ion source. We successfully extracted a V13+ beam with a maximum beam intensity of 600 eµA with 2.8-kW microwave power and 900-W heating power of the HTO. Furthermore, from a systematic study of the dependence of the beam intensity on the microwave power and the HTO power, we successfully produced a V13+ beam of 300 eµA at a consumption rate of 3 mg/h, allowing a one-month duration continuous beam to carry out the SHE synthesis. In addition, to avoid serious damage to newly introduced SC acceleration cavities by beam losses, the beam should be transported with a well-controlled emittance. To efficiently limit the beam emittance, we employed a slit triplet consisting of three pairs of slits installed around the focus point of the low-energy beam transport. The first result of the emittance reduction was observed by a pepper-pot type emittance meter as a function of the acceptance of the slit triplet.

2.
Rev Sci Instrum ; 91(2): 025101, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32113460

RESUMEN

A new RIKEN 28-GHz superconducting electron cyclotron resonance ion source (SC-ECRIS) has been installed for the superconducting RIKEN linear accelerator (SRILAC). The new SC-ECRIS control system mainly consists of programmable logic controllers (PLCs) embedded with the Experimental Physics and Industrial Control System. To improve the reliability as compared with previous control systems, two types of PLC central processing units, sequential and Linux, have been installed in the same unit. Past experience has shown that new types of designs that can rapidly respond to system scalability are key. By connecting PLC stations using star-topology field buses, their rapid and cost-effective response to system changes is realized for the new devices. Furthermore, a unique data acquisition system employing a 920-MHz-band radio was developed to measure analog data such as the temperature at the high-voltage stage.

3.
Oral Dis ; 24(3): 465-475, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28898513

RESUMEN

OBJECTIVES: Sugar consumption has been decreasing in Japan, suggesting higher rates of sucrose-independent supragingival plaque formation. For developing an in vitro biofilm model of sucrose-independent supragingival plaque, this study aimed to investigate the compositions and functions on contributing to cariogenicity in comparison with sucrose-dependent biofilm. MATERIALS AND METHODS: An in vitro multispecies biofilm containing Actinomyces naeslundii, Streptococcus gordonii, S. mutans, Veillonella parvula and Fusobacterium nucleatum was formed on 24-well plates in the absence or presence of 1% sucrose. Compositions were assessed by plate culture, scanning electron microscopy and confocal laser scanning microscopy after fluorescent in situ hybridisation or labelling of extracellular polymeric substances (EPS). Functions were assessed by acidogenicity, adherence strength and sensitivities to anticaries agents. RESULTS: Although both biofilms exhibited a Streptococcus predominant bacterial composition, there were differences in bacterial and EPS compositions; in particular, little glucan EPS was observed in sucrose-independent biofilm. Compared with sucrose-dependent biofilm, acidogenicity, adherence strength and antimicrobial resistance of sucrose-independent biofilm were only slightly lower. However, dextranase degradation was substantially lower in sucrose-independent biofilm. CONCLUSION: Our findings suggest that sucrose-independent biofilm may have cariogenicity as with sucrose-dependent biofilm. These in vitro models can help further elucidate plaque-induced caries aetiology and develop new anticaries agents.


Asunto(s)
Fenómenos Fisiológicos Bacterianos , Biopelículas/efectos de los fármacos , Placa Dental/etiología , Modelos Biológicos , Actinomyces , Caries Dental/microbiología , Fusobacterium nucleatum , Concentración de Iones de Hidrógeno , Hibridación Fluorescente in Situ , Técnicas In Vitro , Microscopía Confocal , Microscopía Electrónica de Rastreo , Streptococcus gordonii , Streptococcus mutans , Sacarosa/farmacología , Edulcorantes/farmacología , Veillonella
4.
Rev Sci Instrum ; 89(12): 123111, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30599547

RESUMEN

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.

5.
J Perinatol ; 37(5): 602-605, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28125093

RESUMEN

OBJECTIVE: To evaluate the effects of levothyroxine (L-T4) supplementation on growth and neurodevelopmental outcomes at 3 years of age in very low birth weight (VLBW) infants with transient hypothyroxinemia of prematurity (THOP). STUDY DESIGN: VLBW infants with plasma thyroid-stimulating hormone concentrations <10 mIU l-1 and free thyroxine concentrations <0.8 ng dl-1 were defined as having THOP and randomly assigned to the Treated (20 infants) or Untreated (31 infants) group. The Treated group received L-T4 at a dose of 5 µg kg-1 day-1. Growth and neurodevelopmental outcomes at 3 years of age were compared between the two groups. RESULTS: There were no significant differences in body length, body weight or head circumference mean s.d. scores or in neurodevelopmental outcomes between the two groups. CONCLUSION: L-T4 supplementation in VLBW infants with THOP demonstrated no beneficial effect at 3 years of age.


Asunto(s)
Hipotiroidismo/tratamiento farmacológico , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Tirotropina/sangre , Tiroxina/administración & dosificación , Tiroxina/sangre , Estatura , Peso Corporal , Cefalometría , Desarrollo Infantil , Preescolar , Femenino , Cabeza/crecimiento & desarrollo , Humanos , Hipotiroidismo/sangre , Recién Nacido , Japón , Masculino , Pruebas de Función de la Tiroides
6.
J Perinatol ; 36(10): 890-6, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27442157

RESUMEN

OBJECTIVES: To evaluate the impact of pulmonary hypertension (PH) on long-term growth and neurodevelopmental outcomes of extremely preterm infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: A single-center retrospective cohort of preterm infants born at <28 weeks gestational age from 2000 to 2011 was evaluated at 3 years of age. Growth and neurodevelopmental outcomes were compared among 3 groups: non-BPD, BPD without PH and BPD with PH. BPD was defined according to oxygen demand at 36 weeks postmenstrual age. PH was diagnosed by echocardiography during the neonatal intensive care unit stay. RESULTS: Sixty-two infants without BPD, 60 with BPD without PH and 20 with BPD with PH were analyzed. Regardless of PH status, somatic growth was smaller in both BPD groups of infants than in non-BPD infants, with further reduction in the group having BPD with PH. Furthermore, a developmental quotient of <70 was more prevalent in the BPD infants with PH than in the BPD infants without PH (odds ratio (OR): 4.37; 95% confidence interval, CI: 1.16 to 16.5). Multivariate analysis demonstrated that BPD with PH was one of the independent perinatal risk factors for developmental quotient <70 at 3 years of age (OR: 4.94, 95% confidence interval: 1.06 to 24.1). CONCLUSION: PH had an additional negative effect on long-term growth and neurodevelopmental outcomes of extremely preterm infants with BPD.


Asunto(s)
Displasia Broncopulmonar/complicaciones , Discapacidades del Desarrollo/etiología , Hipertensión Pulmonar/complicaciones , Recien Nacido Extremadamente Prematuro/crecimiento & desarrollo , Adulto , Peso Corporal , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/epidemiología , Estudios de Casos y Controles , Preescolar , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/epidemiología , Ecocardiografía , Femenino , Edad Gestacional , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/epidemiología , Incidencia , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Estudios Longitudinales , Masculino , Embarazo , Estudios Retrospectivos , Factores de Riesgo
7.
J Neonatal Perinatal Med ; 9(1): 99-105, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27002262

RESUMEN

OBJECTIVE: In order to evaluate safety and usefulness of peripherally inserted double lumen central catheter (PIDLCC) in very low birth weight (VLBW) infants, outcomes of VLBW infants who had PIDLCC was studied. SUBJECTIVE: Thirty-nine VLBW infants who were admitted to our NICU in 2013 were retrospectively analyzed. RESULTS: Mean birth weight and gestational age was 1042.7 gram and 28.5 weeks, respectively. Total duration of indwelling PIDLCC was 1121 days (mean 28.5+18.2 days) with 85 PIDLCCs used. Dressing at the insertion site was done twice weekly with 10% povidone iodine. Four (10.3% with mean of 48 days) infants had catheter-related blood stream infection (CRBSI), with a 3.57 infection per 1000 catheter-day. The mean for days of PIDLCC in 35 infants without CRBSI was 26.5 days. Organisms isolated were Staphylococcus epidermidis, Staphylococcus aureus and Staphylococcus capitis ureolytic. Our study showed significant difference in the duration of indwelling catheter (p = 0.023) and intraventricular hemorrhage (p = 0.043) between the CRBSI group and non-CRBSI group. Five (12.8%) infants had abnormal thyroid function test, in which two infants required thyroxine supplementation upon discharge. However, duration of PIDLCC and abnormal thyroid function test was not statistically significant (p = 0.218). One (2.5%) infant died (death was not related to CRBSI). There was no serious adverse effects secondary to PIDLCC. CONCLUSION: It is concluded that the use and maintenance of PIDLCC is safe for VLBW infants, but close monitoring should be observed to detect early signs of infection.


Asunto(s)
Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres de Permanencia/efectos adversos , Unidades de Cuidado Intensivo Neonatal , Nutrición Parenteral/efectos adversos , Seguridad del Paciente , Infecciones Relacionadas con Catéteres/microbiología , Cateterismo Venoso Central/estadística & datos numéricos , Cateterismo Periférico/estadística & datos numéricos , Catéteres de Permanencia/microbiología , Femenino , Humanos , Recién Nacido , Recién Nacido de muy Bajo Peso , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
8.
Rev Sci Instrum ; 87(2): 02A722, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26931940

RESUMEN

A RIKEN 18 GHz electron cyclotron resonance ion source (18 GHz ECRIS) is used as an external ion source at the Radioactive Ion Beam Factory (RIBF) accelerator complex to produce an intense beam of medium-mass heavy ions (e.g., Ca and Ar). In most components that comprise the RIBF, the control systems (CSs) are integrated by the Experimental Physics and Industrial Control System (EPICS). On the other hand, a non-EPICS-based system has hardwired controllers, and it is used in the 18 GHz ECRIS CS as an independent system. In terms of efficient and effective operation, the 18 GHz ECRIS CS as well as the RIBF CS should be renewed using EPICS. Therefore, we constructed an 18 GHz ECRIS CS by using programmable logic controllers with embedded EPICS technology. In the renewed system, an operational log system was developed as a new feature, for supporting of the 18 GHz ECRIS operation.

9.
Rev Sci Instrum ; 87(2): 02B921, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26932093

RESUMEN

Francium is the heaviest species among the alkali elements. Due to its properties, francium is said to be of advantage in measurements of tiny observations, such as atomic parity violation and electric dipole moment. Before executing experiments with francium, it must be produced artificially because it is one of the most unstable elements. We produced francium with the nuclear fusion reaction of an oxygen beam and gold target, ionized the produced francium through a thermal ionization process, and extracted the ion with electrostatic fields. However, the thermal ionization process is known to ionize not only an objective atom but also other atomic species. Therefore, a Wien filter was installed to analyze the composition of the ion beam and purify the beam. This allowed us to improve the beam purity from ∼10(-6) to ∼10(-3).

10.
Appl Opt ; 55(5): 1164-9, 2016 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-26906392

RESUMEN

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.

11.
Dis Esophagus ; 29(8): 1090-1099, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26541471

RESUMEN

Patients with thoracic esophageal cancer are often treated by minimally invasive esophagectomy. However, the long-term survival benefits of minimally invasive esophagectomy remain unclear. Two approaches are available for thoracoscopic surgery: one with the patient in the left lateral decubitus position (LLDP), and the other with the patient in the prone position (PP). We investigated the survival benefit of thoracoscopic esophagectomy according to the tumor stage and patient position during the thoracoscopic procedure. We reviewed the records of 220 consecutive patients with esophageal cancer treated from 1998 to 2012. In total, 146 and 74 patients were treated with thoracoscopic esophagectomy in the LLDP and PP, respectively. No patients were initially proposed to be candidates for esophagectomy by thoracotomy during the study period. Data collection was performed with a focus on survival and recurrent disease. Among all the 220 patients, the overall 5-year survival rates were 83.7%, 74.1%, 45.5%, 78.6%, 44.2%, 29.4% and 24.3% in the patients with pStage IA, IB, IIA, IIB, IIIA, IIIB and IIIC disease, respectively. Despite the greater number of dissected mediastinal lymph nodes in the PP procedure, there were no significant differences in the survival curves between the LLDP and PP procedures. The long-term results of thoracoscopic esophagectomy are comparable and acceptable. The PP procedure was not confirmed to offer a superior survival benefit to the LLDP procedure in this retrospective study.


Asunto(s)
Neoplasias Esofágicas/cirugía , Esofagectomía/mortalidad , Toracoscopía/mortalidad , Anciano , Neoplasias Esofágicas/mortalidad , Esofagectomía/métodos , Femenino , Humanos , Escisión del Ganglio Linfático/métodos , Escisión del Ganglio Linfático/estadística & datos numéricos , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente/métodos , Posición Prona , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia , Toracoscopía/métodos , Resultado del Tratamiento
13.
Phys Rev Lett ; 113(10): 102501, 2014 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-25238351

RESUMEN

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.

14.
Rev Sci Instrum ; 85(2): 02A732, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24593466

RESUMEN

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.

15.
Rev Sci Instrum ; 85(2): 02A904, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24593483

RESUMEN

The control system for the RIKEN 28 GHz superconducting electron cyclotron resonance ion source (28 GHz SC-ECRIS) consists of a distributed control system based on the experimental physics and industrial control system. To maintain the beam quality for the long beam-service time at the radioactive isotope beam factory, beam tuning to prevent subtle changes in the 28 GHz SC-ECRIS conditions is required. Once this is achieved, it should then be possible to check conditions and operate the ion source at any time. We have designed a web-based operational interface to remotely control the ion source, but for access and control from several locations, suitable access security, policies, and methods are required. We thus implemented an operator intervention system that makes it possible to safely access the network externally with the permission of on-site accelerator operators in the control room.

16.
Aliment Pharmacol Ther ; 36(6): 575-86, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22817400

RESUMEN

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, characterised by thickening of the wall of the right hemicolon with calcification of mesenteric veins. However, the aetiology remains unknown. AIM: To investigate the possible association of herbal medicines with IMP. METHOD: The clinical data of four of our own patients were collected. Furthermore, we searched for previous reports about similar patients with detailed descriptions of herbal prescriptions that they had taken. We compared herbal ingredients to identify the toxic agent as a possible aetiological factor. RESULTS: Clinical data on a total of 25 patients were summarised. Mean age was 61.8 years and there was female predominance (6 men and 19 women). The used Kampo prescription, the number of cases, and the mean duration of use were as follows: kamisyoyosan in 12 cases for 12.8 years, inshin-iseihaito in 5 cases for 13.4 years, orengedokuto in 4 cases for 14.3 years, inchinkoto in 1 case for 20 years, kamikihitou in 1 case for 19 years, seijobofuto in 1 case for 10 years and gorinsan in 1 case for an unknown duration. Only one ingredient, sansisi, was common to the herbal medicines of all 25 patients. This crude drug called geniposide in English is a major constituent of the Gardenia fruits. CONCLUSION: The long-term use of geniposide in herbal medicines appears to be associated with mesenteric phlebosclerosis.


Asunto(s)
Medicamentos Herbarios Chinos/efectos adversos , Iridoides/efectos adversos , Oclusión Vascular Mesentérica/inducido químicamente , Venas Mesentéricas/patología , Plantas Medicinales/efectos adversos , Anciano , Biopsia , Femenino , Humanos , Mucosa Intestinal/patología , Masculino , Oclusión Vascular Mesentérica/diagnóstico por imagen , Oclusión Vascular Mesentérica/patología , Persona de Mediana Edad , Esclerosis/inducido químicamente , Factores de Tiempo , Tomografía Computarizada por Rayos X
17.
Rev Sci Instrum ; 83(2): 02A308, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22380155

RESUMEN

We measured the beam intensity of highly charged heavy ions and x-ray heat load for RIKEN superconducting electron cyclotron resonance ion source with 28 GHz microwaves under the various conditions. The beam intensity of Xe(20+) became maximum at B(min) ∼ 0.65 T, which was ∼65% of the magnetic field strength of electron cyclotron resonance (B(ECR)) for 28 GHz microwaves. We observed that the heat load of x-ray increased with decreasing gas pressure and field gradient at resonance zone. It seems that the beam intensity of highly charged heavy ions with 28 GHz is higher than that with 18 GHz at same RF power.

18.
Rev Sci Instrum ; 83(2): 02A333, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22380180

RESUMEN

A highly charged uranium (U) ion beam is produced from the RIKEN superconducting electron cyclotron resonance ion source using 18 and 28 GHz microwaves. The sputtering method is used to produce this U ion beam. The beam intensity is strongly dependent on the rod position and sputtering voltage. We observe that the emittance of U(35+) for 28 GHz microwaves is almost the same as that for 18 GHz microwaves. It seems that the beam intensity of U ions produced using 28 GHz microwaves is higher than that produced using 18 GHz microwaves at the same Radio Frequency (RF) power.

19.
Br J Cancer ; 106(5): 939-46, 2012 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-22281663

RESUMEN

BACKGROUND: The availability of molecular-targeted therapies for the treatment of melanoma has emphasised the need to identify mutations in target genes such as BRAF and KIT. Circulating tumour cells (CTC) are present in the peripheral blood of a significant proportion of cancer patients. METHODS: High molecular weight melanoma-associated antigen (HMW-MAA) was used to isolate melanoma cells from peripheral blood as it is selectively expressed at high levels on melanomas. The HMW-MAA-positive cells were isolated using immunomagnetic beads. After removing CD45(+) cells, CTC were identified by staining with MART-1- and gp100-specific antibodies (HMW-MAA(+), CD45(-), MART-1/gp100(+)). Single, isolated CTC were then subjected to BRAF and KIT mutational analysis. RESULTS: CTC (HMW-MAA(+), CD45(-), MART-1/gp100(+)) were isolated from the blood of 11 patients and BRAF and KIT were sequenced in nine and four patients, respectively. The BRAF sequences identified in the CTC were inconsistent with those identified in autologous melanoma tumours in three patients and the KIT sequences were inconsistent in three patients. In addition, polyclonal BRAF mutations were identified in one patient and concomitant mutations in BRAF and KIT were identified in another patient. CONCLUSION: Melanoma cells show clonal heterogeneity. Therefore, CTC genotyping may be crucial for successful molecular-targeted therapy.


Asunto(s)
Melanoma/genética , Melanoma/patología , Células Neoplásicas Circulantes , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales , Antígenos de Neoplasias/sangre , Secuencia de Bases , Línea Celular Tumoral , Separación Celular , Análisis Mutacional de ADN , Femenino , Genes ras , Genotipo , Humanos , Separación Inmunomagnética , Antígeno MART-1/sangre , Antígeno MART-1/inmunología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Mutación , Proteínas de Neoplasias/genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Proteínas Proto-Oncogénicas B-raf/sangre , Análisis de Secuencia de ADN , Análisis de la Célula Individual , Neoplasias Cutáneas/genética
20.
Br J Cancer ; 104(3): 464-8, 2011 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-21224857

RESUMEN

BACKGROUND: Oncogenic BRAF mutation had been considered to be a founder event in the formation of melanocytic tumours; however, we recently argued against this notion by showing marked polyclonality of BRAF mutations in acquired melanocytic nevi (Lin et al, J Natl Cancer Inst., 2009; 101:1423-7). Here, we tested whether similar heterogeneity of BRAF mutations exists in primary melanomas. METHODS: We isolated and sequenced single melanoma cells from five primary melanoma tissues using antibodies against human high-molecular-weight melanoma-associated antigen. We also examined 10 primary melanomas by the sensitive Mutector assay detecting the BRAF(V600E) mutation, as well as by cloning and sequencing of separated alleles. Furthermore, we estimated the frequency of BRAF mutant alleles in paired samples of primary tumour and recurrence or metastasis in three patients. RESULTS: Single-cell mutation analyses revealed that four of five primary melanomas contained both BRAF-wild-type and BRAF-mutant tumour cells. Tumour heterogeneity in terms of BRAF mutations was also shown in 8 of 10 primary melanomas. Selection of BRAF mutant alleles during progression was demonstrated in all the three patients. CONCLUSION: Acquisition of a BRAF mutation is not a founder event, but may be one of the multiple clonal events in melanoma development, which is selected for during the progression.


Asunto(s)
Proteínas Proto-Oncogénicas B-raf/genética , Alelos , Línea Celular Tumoral , Células Clonales , Humanos , Melanoma/genética , Mutación , Neoplasias Cutáneas/genética
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