New model of radiation-induced skin ulcer in rats

Our aim was to provide a new animal model for intractable skin ulcers in irradiated rats. Twenty-four rats were irradiated with total single radiographic irradiation doses of 10, 15, 20, and 30 Gy. The skin was observed for 6 months. In the 10-Gy group, there were no visible changes to the skin. In the 15-Gy group, epilation and depigmentation were seen about 2 weeks after irradiation. In the groups over 20-Gy, minor erosion or skin ulcers appeared in most rats. The wounds healed in the 20-Gy group, but many in the 30-Gy group could not be healed. A further 36 rats were irradiated with 20 Gy, and this was followed by the creation of cutaneous full-thickness defects at different periods. The size of the wounds was measured on days 0, 3, 5, 7, 10, and 14. Delayed wound healing was found in the irradiated groups compared with the unirradiated group (p = 0.01). There were no differences in the time of ulceration, except in the Day 7 group (p = 0.03).     

Movement-related activity of thalamic neurons with input from the globus pallidus and projection to the motor cortex in the monkey

Summary Thalamic neurons projecting to the arm area of the motor cortex were identified by their antidromic response to stimulation of that area in two awake monkeys. Neurons were further identified as receiving inputs from the cerebellar nuclei or the internal segment of the globus pallidus by excitatory or inhibitory response to stimulation of these nuclei. Most (33/34) of the thalamic neurons in the cerebello-thalamo-cortical projection and more than half (12/18) of those in the pallido-thalamocortical projection changed their firing rate on the leverlifting hand movement in the reaction-time task. A considerable number of neurons of both groups (14/23 and 3/10) changed their firing rate prior to the onset of the earliest EMG. These findings agree with the model that activities of pallidal as well as cerebellar nuclear neurons related to motor control are transmitted to the motor cortex through the thalamus.     

Functional significance of the cortico-subthalamo-pallidal 'hyperdirect' pathway

How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. The cortico-subthalamo-pallidal 'hyperdirect' pathway conveys powerful excitatory effects from the motor-related cortical areas to the globus pallidus, bypassing the striatum, with shorter conduction time than effects conveyed through the striatum. We emphasize the functional significance of the 'hyperdirect' pathway and propose a dynamic 'center-surround model' of basal ganglia function in the control of voluntary limb movements. When a voluntary movement is about to be initiated by cortical mechanisms, a corollary signal conveyed through the cortico-subthalamo-pallidal 'hyperdirect' pathway first inhibits large areas of the thalamus and cerebral cortex that are related to both the selected motor program and other competing programs. Then, another corollary signal through the cortico-striato-pallidal 'direct' pathway disinhibits their targets and releases only the selected motor program. Finally, the third corollary signal possibly through the cortico-striato-external pallido-subthalamo-internal pallidal 'indirect' pathway inhibits their targets extensively. Through this sequential information processing, only the selected motor program is initiated, executed and terminated at the selected timing, whereas other competing programs are canceled.     

Monkey globus pallidus external segment neurons projecting to the neostriatum.

Experiments were performed to assess the number and parvalbumin (PV) immunoreactivity of neurons participating in the pallidostriatal projection in macaque monkeys. Injection of WGA-HRP into the right caudate nucleus and the left putamen of a Macaca mulatta and a M. fuscata labeled a large number of the globus pallidus external segment (GPe) neurons. Counting neurons labeled with WGA-HRP and those stained with neuronal markers indicated that approximately 30% of GPe neurons project to neostriatum. Approximately 2/3 of the pallidostriatal neurons are PV-immunoreactive. This study revealed that a significant number of primate GPe PV immunoreactive neurons project to the neostriatum, and suggest that the pallidostriatal projection should be taken into account in the analysis of functional roles of the basal ganglia circuitry.     

Wavelet compression on detection of brain lesions with magnetic resonance imaging

The purpose of this report is to assess clinically acceptable compression ratios on the detection of brain lesions at magnetic resonance imaging (MRI). Four consecutive T2-weighted and the corresponding T1-weighted images obtained in 20 patients were studied for 109 anatomic sites including 50 with lesions and 59 without lesions. The images were obtained on a 1.5-T MR unit with a pixel size of 0.9 to 1.2 x 0.47 mm and a section thickness of 5 mm. The image data were compressed by wavelet-based algorithm at ratios of 20:1, 40:1, and 60:1. Three radiologists reviewed these images on an interactive workstation and rated the presence or absence of a lesion with a 50 point scale for each anatomic site. The authors also evaluated the influence of pixel size on the quality of image compression. At receiver operating characteristic (ROC) analysis, no statistically significant difference was detected at a compression ratio of 20:1. A significant difference was observed with 40:1 compressed images for one reader (P = .023), and with 60:1 for all readers (P = .001 to .012). A root mean squared error (RMSE) was higher in 0.94- x 0.94-mm pixel size images than in 0.94- x 0.47-mm pixel size images at any compression ratio, indicating compression tolerance is lower for the larger pixel size images. The RMSE, subjective image quality, and error images of 10:1 compressed 0.94- x 0.94-mm pixel size images were comparable with those of 20:1 compressed 0.94- x 0.47-mm pixel size images. Wavelet compression can be acceptable clinically at ratios as high as 20:1 for brain MR images when a pixel size at image acquisition is around 1.0 x 0.5 mm, and as high as 10:1 for those with a pixel size around 1.0 x 1.0 mm.     

Abundant expression of the intestinal protein villin in Barrett's metaplasia and esophageal adenocarcinomas

Villin is a cytoskeletal protein that is involved in the formation of brush-border microvilli in normal small intestine and colon epithelium. This protein is present in Barrett's metaplasia but is reported not to be expressed in Barrett's adenocarcinoma. In this study, we analyzed villin protein expression in Barrett's metaplasia and in both Barrett's adenocarcinomas and tumors of the gastric cardia. Immunohistochemical analysis was used to evaluate the expression and cellular localization of the villin protein in 21 cases of Barrett's metaplasia, 30 cases of Barrett's adenocarcinoma, 16 cases of gastric cardia adenocarcinoma, and eight cases of adenocarcinoma of the distal esophagus. Southern, northern, and western blot analyses were used to evaluate the potential mechanisms for regulation of villin protein expression. Villin protein expression was observed in 21 of 21 cases (100%) of intestinal-type Barrett's metaplasia and in 28 of 30 cases (93%) of Barrett's adenocarcinoma and was thus highly expressed in these tumors. Northern blot analysis demonstrated villin mRNA (3.5 and 2.7 kb) in both villin-positive Barrett's metaplasia and adenocarcinomas. Western blot analysis with the antibody used for immunohistochemical analysis confirmed the presence of a single villin protein band of 95 kDa. Abundant villin expression also was present in both adenocarcinoma of the gastric cardia (13 of 16 cases; 81%) and distal esophageal adenocarcinomas of unknown origin (six of eight cases; 75%). The intestinal brush-border enzyme sucrase isomaltase was found to be present in only 22 of 46 cases (48%) of the adenocarcinomas that expressed villin. We concluded that the protein villin is highly expressed in Barrett's adenocarcinomas and is well maintained in these and other esophageal tumors. Mol. Carcinog. 22:182–189, 1998. © 1998 Wiley-Liss, Inc.     

Fabricated CAD/CAM Post-Core Using Glass Fiber-Reinforced Resin Shows Innovative Potential in Restoring Pulpless Teeth

The prevention of root fractures of pulpless teeth is an important clinical issue to maintain healthy teeth through lifetime. The aim of this study was to examine a clinically effective treatment method for strengthening vulnerable pulpless teeth using CAD/CAM (computer-aided design/computer-aided manufacturing) fiber-reinforced post-core by conducting a fracture resistance test. A post-core made with a fiber-reinforced resin disk TRINIA (TR, SHOFU, Kyoto, Japan) was fabricated using a CAD/CAM system. The fiber-layer orientation of the CAD/CAM post-core was parallel to the axis of the restored tooth. A post-core using a conventional composite and a fiber post (CF) was also prepared. A fracture resistance test of teeth restored with the post-cores and zirconia crowns was conducted using a universal testing machine, and fracture patterns were identified by micro-CT observation. The fracture load of the roots restored with TR was 1555.9 ± 231.8 N, whereas that of CF was 1082.1 ± 226.7 N. The fracture load of TR was 43.8% that was significantly higher than that of CF (Student’s t-test, p < 0.05). The restored teeth with CAD/CAM resin post-core were found to be repairable even after fracture. These results suggest that the CAD/CAM indirect fiber post-core has the potential to strengthen the vulnerable pulpless teeth.     

The subthalamic nucleus‐external globus pallidus loop biases exploratory decisions towards known alternatives: a neuro‐computational study

Theories and models of the basal ganglia have mainly focused on the role of three different corticothalamic pathways: direct, indirect and hyperdirect. Although the indirect and the hyperdirect pathways are linked through the bidirectional connections between the subthalamic nucleus (STN) and the external globus pallidus (GPe), the role of their interactions has been mainly discussed in the context of a dysfunction (abnormal oscillations in Parkinson's disease) and not of its function. We here propose a novel role for the loop formed by the STN and the GPe. We show, through a neuro‐computational model, that this loop can bias the selection of actions during the exploratory period after a change in the environmental conditions towards alternative responses. Testing well‐known alternative solutions before completely random actions can reduce the time required for the search of a new response after a rule change. Our simulations further show that the knowledge acquired by the indirect pathway can be transferred into a stable memory via learning in the hyperdirect pathway to establish the blocking of unwanted responses. After a rule switch, first the indirect pathway learns to inhibit the previously correct actions. Once the new correct association is learned, the inhibition is transferred to the hyperdirect pathway through synaptic plasticity.     

Subthalamo-pallidal interactions underlying parkinsonian neuronal oscillations in the primate basal ganglia

Parkinson’s disease is characterized by degeneration of nigral dopaminergic neurons, leading to a wide variety of psychomotor dysfunctions. Accumulated evidence suggests that abnormally synchronized oscillations in the basal ganglia contribute to the expression of parkinsonian motor symptoms. However, the mechanism that generates abnormal oscillations in a dopamine‐depleted state remains poorly understood. We addressed this question by examining basal ganglia neuronal activity in two 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐treated parkinsonian monkeys. We found that systemic administration of l ‐3,4‐dihydroxyphenylalanine (l ‐DOPA; dopamine precursor) decreased abnormal neuronal oscillations (8–15 Hz) in the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) during the ON state when parkinsonian signs were alleviated and during l ‐DOPA‐induced dyskinesia. GPi oscillations and parkinsonian signs were suppressed by silencing of the STN with infusion of muscimol (GABA_A receptor agonist). Intrapallidal microinjection of a mixture of 3‐(2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid (CPP; N‐methyl‐d ‐aspartate receptor antagonist) and 1,2,3,4‐tetrahydro‐6‐nitro‐2,3‐dioxo‐benzo[f]quinoxaline‐7‐sulfonamide (NBQX; AMPA/kainate receptor antagonist) also decreased the oscillations in the GPi and the external segment of the globus pallidus (GPe). Neuronal oscillations in the STN were suppressed after intrasubthalamic microinjection of CPP/NBQX to block glutamatergic afferents of the STN. The STN oscillations were further reduced by muscimol inactivation of the GPe to block GABAergic inputs from the GPe. These results suggest that, in the dopamine‐depleted state, glutamatergic inputs to the STN and reciprocal GPe–STN interconnections are both important for the generation and amplification of the oscillatory activity of STN neurons, which is subsequently transmitted to the GPi, thus contributing to the symptomatic expression of Parkinson’s disease.