RESUMEN
Genetic reversion is the phenomenon of spontaneous gene correction by which gene function is partially or completely rescued. However, it is unknown whether this mechanism always correctly repairs mutations, or is prone to error. We investigated a family of three boys with intellectual disability, and among them we identified two different mutations in KDM5C, located at Xp11.22, using whole-exome sequencing. Two affected boys have c.633delG and the other has c.631delC. We also confirmed de novo germline (c.631delC) and low-prevalence somatic (c.633delG) mutations in their mother. The two mutations are present on the same maternal haplotype, suggesting that a postzygotic somatic mutation or a reversion error occurred at an early embryonic stage in the mother, leading to switched KDM5C mutations in the affected siblings. This event is extremely unlikely to arise spontaneously (with an estimated probability of 0.39-7.5 × 10(-28) ), thus a possible reversion error is proposed here to explain this event. This study provides evidence for reversion error as a novel mechanism for the generation of somatic mutations in human diseases.
Asunto(s)
Histona Demetilasas/genética , Discapacidad Intelectual/genética , Herencia Materna/genética , Mutación/genética , Preescolar , Exoma , Femenino , Genes Ligados a X , Haplotipos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Discapacidad Intelectual/fisiopatología , Masculino , Mosaicismo , Madres , Linaje , FenotipoRESUMEN
The halo structure of 31Ne is studied using 1n-removal reactions on C and Pb targets at 230 MeV/nucleon. A combined analysis of the cross sections of these nuclear and Coulomb dominated reactions that feed directly the 30Ne ground-state reveals 31Ne to have a small neutron separation energy, 0.15(-0.10)(+0.16) MeV, and spin-parity 3/2-. Consistency of the data with reaction and large-scale shell-model calculations identifies 31Ne as deformed and having a significant p-wave halo component, suggesting that halos are more frequent occurrences at the neutron drip line.
RESUMEN
Trimetaphosphate (TMP) effects on demineralized bovine enamel were studied after 15 days of pH cycling. Treatments included 30 wt% (weight percent) dilutions of 0, 500, 1,500 or 3,000 µg F/g aqueous NaF solutions with or without 3% TMP. Treated specimens were assessed by transverse microradiography. With the exception of the 3,000 µg F/g case, 3% TMP addition provided significant additional overall remineralization compared with F alone. Mineral content profiles differed significantly between corresponding F and F + TMP groups. Fluoride alone resulted in more remineralization in the original demineralized zone, whereas F + TMP caused less demineralization in the underlying, originally sound enamel.
Asunto(s)
Cariostáticos/administración & dosificación , Esmalte Dental/efectos de los fármacos , Polifosfatos/administración & dosificación , Fluoruro de Sodio/administración & dosificación , Desmineralización Dental/fisiopatología , Remineralización Dental/métodos , Animales , Bovinos , Precipitación Química , Cristalización , Esmalte Dental/patología , Combinación de Medicamentos , Concentración de Iones de Hidrógeno , Microrradiografía , Minerales/análisis , Factores de TiempoRESUMEN
Reaction cross sections (sigma(R)) for 19C, 20C and the drip-line nucleus 22C on a liquid hydrogen target have been measured at around 40A MeV by a transmission method. A large enhancement of sigma(R) for 22C compared to those for neighboring C isotopes was observed. Using a finite-range Glauber calculation under an optical-limit approximation the rms matter radius of 22C was deduced to be 5.4+/-0.9 fm. It does not follow the systematic behavior of radii in carbon isotopes with N < or = 14, suggesting a neutron halo. It was found by an analysis based on a few-body Glauber calculation that the two-valence neutrons in 22C preferentially occupy the 1s(1/2) orbital.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Ácido Hialurónico/uso terapéutico , Obstrucción Intestinal/prevención & control , Laparoscopía/métodos , Complicaciones Posoperatorias/prevención & control , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Obstrucción Intestinal/etiología , Intestino Delgado/patología , Masculino , Ilustración Médica , Membranas Artificiales , Persona de Mediana Edad , Cavidad Peritoneal/cirugía , Complicaciones Posoperatorias/etiología , Adherencias Tisulares/etiología , Adherencias Tisulares/prevención & controlRESUMEN
BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.
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Tronco Encefálico/anomalías , Venas Cerebrales/anomalías , Síndrome de Walker-Warburg/diagnóstico por imagen , Adolescente , Tronco Encefálico/diagnóstico por imagen , Venas Cerebrales/diagnóstico por imagen , Niño , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Neuroimagen/métodos , Estudios Retrospectivos , Adulto JovenRESUMEN
The cross sections for single-neutron removal from the very neutron-rich nucleus 31Ne on Pb and C targets have been measured at 230 MeV/nucleon using the RIBF facility at RIKEN. The deduced large Coulomb breakup cross section of 540(70) mb is indicative of a soft E1 excitation. Comparison with direct-breakup model calculations suggests that the valence neutron of 31Ne occupies a low-l orbital (most probably 2p(3/2)) with a small separation energy (S(n) approximately < 0.8 MeV), instead of being predominantly in the 1f(7/2) orbital as expected from the conventional shell ordering. These findings suggest that 31Ne is the heaviest halo system known.
RESUMEN
One way to reduce dental fluorosis is by reducing the fluoride (F) concentration in dentifrice, but low-F dentifrice should be as effective as a standard dentifrice. This study evaluated in vitro whether the supplementation with sodium trimetaphosphate (TMP) of a dentifrice with low F content (500 microg/g) would provide a similar effect to that of a standard dentifrice. Bovine enamel blocks were submitted to a pH cycling regime incorporating daily exposures to a slurry of dentifrice: a low-F dentifrice with or without 0.1-3.0% TMP; an F-free, phosphate-free dentifrice (negative control), or a dentifrice with 1,100 microg/g F (positive control). The addition of TMP to dentifrice with or without F was associated with higher surface hardness and decreased loss of integrated subsurface hardness after pH cycling. The combination of 1% TMP and 500 microg F/g had a greater effect than the positive control dentifrice. It is concluded that the addition of TMP to the 500-microg F/g dentifrice allowed a similar or larger effect as compared with a standard dentifrice in this in vitro model.
Asunto(s)
Cariostáticos/administración & dosificación , Esmalte Dental/química , Dentífricos/química , Polifosfatos/administración & dosificación , Fluoruro de Sodio/administración & dosificación , Remineralización Dental/métodos , Animales , Calcio/análisis , Bovinos , Análisis del Estrés Dental , Combinación de Medicamentos , Fluoruros/análisis , Fluorosis Dental/prevención & control , Dureza , Fosfatos/análisis , Desmineralización Dental/terapiaRESUMEN
A polymorphism in the gene for cholesteryl ester transfer protein (CETP) has been reported to be associated with serum cholesterol levels and risk for atherosclerotic vascular diseases, and to clarify the relationship between the gene polymorphism for CETP and macroangiopathy in diabetes mellitus, a cross-sectional study was performed. The subjects of the study were182 Japanese (age: 59.6+/-8.6 years) with type 2 diabetes and no signs of renal dysfunction, 24 of whom had macroangiopathy, and 158 of whom did not. The genotype of the subjects for the TaqIB polymorphism of CETP in intron one was analyzed by using polymerase chain reaction - restriction fragment length polymorphism. Serum CETP levels were significantly higher in the B1/B1 genotype than in the other genotypes (P<0.05). The serum CETP levels were correlated with the serum LDL cholesterol levels (P<0.01), but not with the HDL cholesterol levels. Macroangiopathy was more frequently observed in subjects with the B1/B1 genotype than in the other genotypes (odds ratio=2.953, 95% confidence interval=1.250-6.977, P=0.0136). Logistic regression analysis revealed that the CETP genotype was independently associated with macroangiopathy. The exact mechanism underlying the association remains unknown, but differences in serum CETP levels may be involved.
Asunto(s)
Pueblo Asiatico/genética , Proteínas Portadoras/genética , Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas/genética , Glicoproteínas , Polimorfismo Genético , Anciano , Proteínas Portadoras/sangre , Estudios de Casos y Controles , Proteínas de Transferencia de Ésteres de Colesterol , Estudios Transversales , Angiopatías Diabéticas/sangre , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Japón , Lipoproteínas/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica)RESUMEN
It has been reported that patients with essential hypertension have high plasma prolactin levels and suggested that reduced central dopaminergic activity may be a factor in the pathogenesis of essential hypertension. This study examines the influence of posture on plasma prolactin, plasma catecholamines, plasma renin activity, blood pressure and heart rate in 24 patients with borderline hypertension (age 19 +/- 1 years) and 20 normotensive subjects matched for age and body mass index. Supine plasma prolactin levels were similar in both groups [borderline hypertension, 11.3 +/- 0.7 ng/ml; normotensive, 10.7 +/- 0.8 ng/ml (mean +/- s.e.m.)] and no increase in plasma prolactin was observed after 10 min standing in both groups. Normotensive and borderline hypertensive subjects had similar values for supine and upright plasma renin activity and plasma norepinephrine. There were no significant correlations between supine plasma prolactin and supine blood pressure, supine plasma renin activity or plasma norepinephrine when data from both normotensive and borderline hypertensive subjects were combined. These results may provide indirect evidence against the occurrence of reduced central dopaminergic activity in borderline hypertension.
Asunto(s)
Epinefrina/sangre , Hipertensión/sangre , Norepinefrina/sangre , Prolactina/sangre , Renina/sangre , Adulto , Creatinina/sangre , Humanos , Masculino , Postura , Potasio/sangre , Descanso , Sodio/sangreRESUMEN
To define the role of the renal dopaminergic system in the pathogenesis of essential hypertension, urinary free dopamine excretion was examined in 23 normotensive subjects who had one or more first-degree relatives with essential hypertension, and also in 36 matched control subjects without any such family history. The group urinary dopamine excretion and urinary sodium excretion were not different. However, a significant urine dopamine-sodium relationship was apparent in the controls but not in the relatives due to relatively high dopamine output in those with lower sodium excretion. The two groups were similar as regards blood pressure (BP), plasma renin activity (PRA), prolactin and catecholamines. These findings demonstrate an alteration in the urine dopamine-sodium relationship in some normotensive subjects with genetic risk of hypertension.
Asunto(s)
Dopamina/orina , Hipertensión/genética , Adulto , Presión Sanguínea , Catecolaminas/sangre , Humanos , Hipertensión/etiología , Hipertensión/orina , Masculino , Prolactina/sangre , Renina/sangre , Sodio/orinaRESUMEN
Plasma and urine norepinephrine, epinephrine and home blood pressure were measured in 48 young hypertensive men (mean age, 21 years) and 25 matched normotensive controls. Plasma samples were drawn following 30 min rest in the clinic and 24 h urine samples were collected at home. Twenty-one hypertensive patients were given a single dose of clonidine (150 micrograms orally). Changes in blood pressure, heart rate and plasma norepinephrine were assessed. Twenty-five of the hypertensive patients were found to have a normal home blood pressure (defined from records of the normotensive subjects). The other group of patients maintained a high home blood pressure. In comparison to normal subjects, patients with a high home blood pressure were characterized by higher urinary norepinephrine and epinephrine excretion and higher plasma epinephrine. Patients with a normal home blood pressure had normal heart rate at home, normal plasma and urinary catecholamines. However, the two groups of hypertensives could not be distinguished on the basis of clinic blood pressure, plasma or urinary catecholamines due to considerable overlap. At 90 min after oral clonidine administration, the plasma norepinephrine and blood pressure levels were decreased in both groups of hypertensives to a similar extent. The changes in heart rate were significantly smaller in patients with a high home blood pressure than in those with a normal home blood pressure. These results suggest that the patients with a high home blood pressure tended to have a high sympathetic nerve activity. However, the two groups of hypertensives could not be separated on the basis of plasma or urinary catecholamine measurements.
Asunto(s)
Determinación de la Presión Sanguínea , Presión Sanguínea , Clonidina/uso terapéutico , Epinefrina/metabolismo , Hipertensión/fisiopatología , Monitoreo Fisiológico , Norepinefrina/metabolismo , Administración Oral , Adolescente , Adulto , Instituciones de Atención Ambulatoria , Presión Sanguínea/efectos de los fármacos , Clonidina/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Masculino , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
This study was designed to investigate the possibility of sex and age differences in the insulin-blood pressure relationship in a general Japanese population with a wide age range. Fasting serum insulin, lipids, plasma glucose, blood pressure and anthropometric measurements were made on 1,537 men and 843 women aged 16 to 65 years. Of the 2,380 subjects in the present analysis, 290 (184 men, 106 women) were hypertensive. When divided into four age groups (16 to 17, 21 to 22, 30 to 49 and 50 to 65 years), the male hypertensive subjects were found to have significantly higher fasting insulin levels, triglycerides levels and body mass index and lower glucose/insulin ratios than normotensive male subjects in all age groups. In the women, there was no significant difference in serum insulin levels or glucose insulin ratios between the hypertensive and normotensive groups in any age group. Simple correlation analysis showed that blood pressure was statistically significantly correlated with serum insulin levels and body mass index in the men in all age groups. In women, the correlation between blood pressure and serum insulin was insignificant in the 21- to 22-year-old age group. In men but not women, multivariate analysis showed that blood pressure was significantly and independently correlated with fasting serum insulin levels. The results of this study suggests the existence of sex and age differences in the insulin-blood pressure relationship in a Japanese population.
Asunto(s)
Hipertensión , Resistencia a la Insulina , Adolescente , Adulto , Factores de Edad , Anciano , Presión Sanguínea , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Factores SexualesRESUMEN
Plasminogen activator inhibitor-1 (PAI-1) has a central role in the regulation of the fibrinolytic enzyme system. An elevated plasma PAI-1 level is associated with thrombotic disorders. In vitro and in vivo studies indicate that the renin-angiotensin system is involved in the regulation of PAI-1. A 287-bp insertion/deletion (I/D) polymorphism in the gene-encoding angiotensin converting enzyme (ACE) is associated with cardiovascular disorders. We evaluated the association between the ACE I/D polymorphism and plasma PAI-1 antigen levels in 110 healthy Japanese male subjects. Subjects with the D-allele of the gene-encoding ACE had higher levels of PAI-1 (26.3 +/- 14.7 ng/ml, mean +/- standard deviation) compared with those without (21.0 +/- 12.0; P = 0.0491). A multiple linear regression model with independent variables (age, body-mass index, total cholesterol level, triglyceride level, ACE I/D genotype, and PAI-1 genotype due to a single guanine I/D polymorphism in the PAI-1 gene) demonstrated that the triglyceride level (P = 0.0059) and ACE I/D genotype (P = 0.0372) were independent predictors of plasma PAI-1 antigen levels in a subset of the subjects without diabetes mellitus that were not taking lipid-lowering drugs. These findings suggest that the ACE I/D polymorphism is a genetic factor for the regulation of plasma PAI-1 antigen levels in the healthy Japanese population.
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Antígenos/sangre , Peptidil-Dipeptidasa A/genética , Inhibidor 1 de Activador Plasminogénico/inmunología , Adulto , Índice de Masa Corporal , Colesterol/sangre , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Japón/epidemiología , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación Puntual , Polimorfismo Genético , Regiones Promotoras Genéticas , Triglicéridos/sangre , Enfermedades Vasculares/etiologíaRESUMEN
Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 +/- 0.81, 1.65 +/- 0.63, and 0.93 +/- 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P < 0.0001). This association was evident for each group studied (P < 0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels.
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Enfermedades Cardiovasculares/etiología , Factor XIIa/metabolismo , Anciano , Alelos , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/genética , Precursores Enzimáticos/sangre , Factor XIIa/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Factores de RiesgoRESUMEN
The possibility that a familial background of hypertension might influence the blood pressure response to a calcium entry blocker was evaluated in 15 normotensive relatives of patients with essential hypertension and 18 normotensive subjects with no family history of hypertension. Under control conditions, blood pressure, heart rate, plasma noradrenaline, adrenaline, and renin activity did not differ between the two groups. Nifedipine, at a dose of 10 mg administered sublingually, lowered the blood pressure and increased the heart rate, plasma noradrenaline, and renin activity. The normotensive relatives of patients with essential hypertension did not differ in their responses from the normotensive subjects with no family history of hypertension, with the exception of plasma noradrenaline thirty minutes after nifedipine. These results provide evidence to suggest that there is no functional abnormality with increased dependency of vascular smooth muscle tone on calcium influx in the prehypertensive state.
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Presión Sanguínea/efectos de los fármacos , Hipertensión/genética , Nifedipino/farmacología , Adulto , Epinefrina/sangre , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Masculino , Norepinefrina/sangre , Renina/sangreRESUMEN
The effects of the angiotensin-converting enzyme inhibitor captopril on blood pressure, heart rate, plasma prolactin, and renin activity were examined in a single-blind, placebo-controlled trial on 30 patients with essential hypertension (15 given drug, 15 placebo). Captopril, 25 mg administered orally, reduced the blood pressure and increased the plasma renin activity. Captopril decreased mean plasma prolactin from 17.5 +/- 1.4 ng/mL to 9.1 +/- 1.0 ng/mL (p less than 0.001). Significant correlation was found between captopril-induced change from control values of plasma prolactin (delta plasma prolactin) vs delta plasma renin activity (r = -0.688, p less than 0.001). These results suggest that acute administration of captopril was accompanied by a reduction in plasma prolactin and that this reduction may be of clinical significance during therapy of hypertension.
Asunto(s)
Captopril/farmacología , Hipertensión/tratamiento farmacológico , Prolactina/sangre , Adulto , Presión Sanguínea/efectos de los fármacos , Captopril/uso terapéutico , Ensayos Clínicos como Asunto , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Renina/sangre , Método Simple CiegoRESUMEN
The effects of L-dopa on blood pressure, heart rate, plasma renin activity, norepinephrine, epinephrine and prolactin were studied in a randomized single-blind trial in 36 patients with essential hypertension. In response to L-dopa, 250 mg administered orally, the blood pressure decreased significantly as compared with the results of placebo treatment. The heart rate and plasma norepinephrine and epinephrine were unchanged. The plasma renin activity and prolactin decreased as a result of L-dopa administration. The administration of a peripheral DA2 dopamine receptor blocker, domperidone (20 mg, orally) prevented the L-dopa-induced reduction in plasma prolactin but failed to block the fall in blood pressure and plasma renin activity. These results suggest that the blood pressure-lowering effect of L-dopa may be mediated through multiple sites involving D1 dopamine receptors, the central nervous system, and the renin-angiotensin system.
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Hipertensión/tratamiento farmacológico , Levodopa/uso terapéutico , Adulto , Presión Sanguínea/efectos de los fármacos , Epinefrina/sangre , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Norepinefrina/sangre , Renina/sangre , Sistema Renina-Angiotensina/efectos de los fármacos , Método Simple CiegoRESUMEN
We evaluated 443 outpatients and inpatients in Keio University Hospital between 1994 and 1999. Morphologic features from peripheral blood and bone marrow aspiration were evaluated in our hematology laboratory, using Wright-Giemsa, peroxidase staining films and other cytochemistry. Immunophenotype was determined by cell surface antigen analysis by laser flow cytometry, FACscan, using various monoclonal antibodies. Information on cytogenetic and molecular genetic characteristics can be also integrated for diagnosis. One hundred fifty patients were diagnosed with acute leukemia, in which 59 cases were ALL and 91 cases were AML. Seventy-four cases were MDS, 76 cases were myeloproliferative disorders, 21 cases were CLL related disorders, 104 patients were malignant lymphoma, and 18 cases were multiple myeloma. The ratio of male to female was 1.7. The probability of diagnostic rate by Immunophenotyping was estimated by Discriminant analysis in 189 patients, using multivariate analysis of immunophenotype compared to morphology. The average probability by immunophenotypic analysis for diagnostic rate was 91.7%, in which the probability for NHL was very high of 97.1%. Thus, morphologic and immunophenotypic analysis is most essential and basic approach in laboratory hematology, from the perspective of rapid and precise diagnostic methods. Recent advance appreciates the rapid contribution for diagnosis by immunophenotypic analysis. Furthermore, Tele-hematology would contribute the standardization for morphologic method in the near future.
Asunto(s)
Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/inmunología , Inmunofenotipificación , Células de la Médula Ósea/patología , Diagnóstico Diferencial , Femenino , Citometría de Flujo , Neoplasias Hematológicas/sangre , Humanos , MasculinoRESUMEN
An ECR ion source of Gunma University Heavy Ion Medical Center, so-called KeiGM [M. Muramatsu, A. Kitagawa, Y. Sakamoto, S. Sato, Y. Sato, H. Ogawa, S. Yamada, H. Ogawa, Y. Yoshida, and A. G. Drentje, Rev. Sci. Instrum. 76, 113304 (2005)], has been operated for cancer therapy and physical/biological experiment since 2010. KeiGM produces typically 230 µA of 10 keV/u C(4+) ions from CH4 gases. The vacuum pressure is kept between 1.2 × 10(-4) and 1.7 × 10(-4) Pa so as to suppress the pulse-to-pulse current fluctuation within ±10%. The extraction electrode is cleaned every 6-8 months in order to remove deposited carbon, which increases the leak current and discharge. In order to investigate the possibility of long-term operation without such maintenances, oxygen aging for the cleaning of the extraction electrode has been tested in the test bench. The same-designed ion sources at National Institute of Radiological Sciences and SAGA Heavy Ion Medical Accelerator in Tosu (SAGA-HIMAT) are also operated with stable C(4+) current, which are suitable for the continuous operation for cancer therapy.