RESUMEN
DYT1 dystonia is a debilitating movement disorder characterized by repetitive, unintentional movements and postures. The disorder has been linked to mutation of the TOR1A/DYT1 gene encoding torsinA. Convergent evidence from studies in humans and animal models suggest that striatal medium spiny neurons and cholinergic neurons are important in DYT1 dystonia. What is not known is how torsinA dysfunction in these specific cell types contributes to the pathophysiology of DYT1 dystonia. In this study we sought to determine whether torsinA dysfunction in cholinergic neurons alone is sufficient to generate the sensorimotor dysfunction and brain changes associated with dystonia, or if torsinA dysfunction in a broader subset of cell types is needed. We generated two genetically modified mouse models, one with selective Dyt1 knock-out from dopamine-2 receptor expressing neurons (D2KO) and one where only cholinergic neurons are impacted (Ch2KO). We assessed motor deficits and performed in vivo 11.1 T functional MRI to assess sensory-evoked brain activation and connectivity, along with diffusion MRI to assess brain microstructure. We found that D2KO mice showed greater impairment than Ch2KO mice, including reduced sensory-evoked brain activity in key regions of the sensorimotor network, and altered functional connectivity of the striatum that correlated with motor deficits. These findings suggest that (1) the added impact of torsinA dysfunction in medium spiny and dopaminergic neurons of the basal ganglia generate more profound deficits than the dysfunction of cholinergic neurons alone, and (2) that sensory network impairments are linked to motor deficits in DYT1 dystonia.
Asunto(s)
Encéfalo/metabolismo , Distonía Muscular Deformante/metabolismo , Locomoción/fisiología , Chaperonas Moleculares/metabolismo , Red Nerviosa/metabolismo , Animales , Encéfalo/diagnóstico por imagen , Distonía Muscular Deformante/diagnóstico por imagen , Distonía Muscular Deformante/genética , Técnicas de Silenciamiento del Gen/métodos , Masculino , Ratones , Ratones Noqueados , Chaperonas Moleculares/genética , Red Nerviosa/diagnóstico por imagenRESUMEN
A modeling investigation was performed to choose moderator material and size for creating optimal epithermal neutron beams for BNCT based on a proton accelerator and the (7)Li(p,n)(7)Be reaction as a neutrons source. An optimal configuration is suggested for the beam shaping assembly made from polytetrafluoroethylene and magnesium fluorine to be placed on high current IPPE proton accelerator KG-2.5. Results of calculation were experimentally tested and are in good agreement with measurements.
Asunto(s)
Terapia por Captura de Neutrón de Boro/instrumentación , Neutrones Rápidos/uso terapéutico , Aceleradores de Partículas , Terapia por Captura de Neutrón de Boro/estadística & datos numéricos , Simulación por Computador , Arquitectura y Construcción de Instituciones de Salud , Humanos , Método de Montecarlo , Neoplasias/radioterapia , Fantasmas de Imagen , Dosificación RadioterapéuticaRESUMEN
Neutron yields and energy spectra have been measured for various deuteron-induced reactions at low energy. Neutrons of energy > 100 keV emitted in the 9Be(d,n)10B, 12C(d,n)13N, and 13C(d,n)14N reactions at Ed= 1.5 MeV were detected at five angles by means of liquid scintillator detectors. While low-energy neutrons were observed in all studied reactions, only 13C(d,n)14N is characterized by a relatively large yield with spectral features potentially interesting for an accelerator-based neutron source for BNCT.
Asunto(s)
Terapia por Captura de Neutrón/instrumentación , Terapia por Captura de Neutrón/métodos , Planificación de la Radioterapia Asistida por Computador , Berilio/uso terapéutico , Boro/uso terapéutico , Carbono/uso terapéutico , Isótopos de Carbono , Nitrógeno/uso terapéutico , Radioisótopos de Nitrógeno/uso terapéuticoRESUMEN
A new beam line for radiotherapy and radiosurgery with accelerated helium-ion beams has been set up at the Bevalac. The new treatment room has been equipped with a very precise patient positioner in order to utilize the superior dose localization properties of light-ion beams. The beam spreading and shaping system is described, the trade-offs involved in positioning the beam modifying devices are discussed, and the physical properties of the generated radiation fields are reported. The Bragg peak modulation by axial beam stacking employing a variable range shifter is explained and the control system including beam monitoring and dosimetry is presented.
Asunto(s)
Helio , Aceleradores de Partículas , Radioterapia de Alta Energía , Técnicas Estereotáxicas , Humanos , IonesRESUMEN
A system for spreading relativistic heavy ion beams into large uniform radiation fields has been developed. The charged particles passing through the system are deflected into azimuthally symmetric distributions which can then be superimposed to produce dose distributions as large as 30 cm in diameter with less than +/- 3.5% variation in uniformity.
Asunto(s)
Aceleradores de Partículas , Radioterapia/instrumentación , Iones , MagnetismoRESUMEN
A direct data link between a CT scanner and a radiation treatment planning system has been developed. The link transmits the data serially over a coaxial cable using the pseudo-paper-tape punch and reader (serial PIO) interfaces. The data transmission rate with error-check is approximately 25,000 8-bit bytes/s. This translates to about 7 s for transferring a CT scan with a 320-pixel diameter.
Asunto(s)
Computadores , Sistemas de Comunicación en Hospital , Neoplasias/radioterapia , Planificación de Atención al Paciente/métodos , Tomografía Computarizada por Rayos X/instrumentación , Humanos , Neoplasias/diagnóstico por imagenRESUMEN
Mice bearing L1210 leukemia did not show impaired humoral or cellular immune response to antigenic stimulation druing the early stage of the tumor, and a depressed response was noted only in the terminal stage. L1210 cells were shown to suppress inflammatory reaction in vivo.