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Biomedical subjects

Yuji Nagai

Publications and source records attributed to Yuji Nagai.

5 recordsLinked to original sources

Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: an imaging tool for glial cells in the brain.

Peripheral benzodiazepine receptor (PBR) is expressed in most organs and its expression is reported to be increased in activated microglia in the brain. [(11)C]PK11195 has been widely used for the in vivo imaging of PBRs, but its signal in the brain was not high enough for stable quantitative analysis. We synthesized a novel positron emission tomography (PET) ligand, [(11)C]DAA1106, for PBR and investigated its in vivo properties in rat and monkey brain. High uptake of [(11)C]DAA1106 was observed in the olfactory bulb and choroid plexus area, followed by the pons/medulla and cerebellum by in vivo autoradiography of rat brain, correlating with the binding in vitro. [(11)C]DAA1106 binding was increased in the dorsal hippocampus with neural destruction, suggesting glial reaction. [(11)C]DAA1106 binding was both inhibited and displaced by 1.0 mg/kg of DAA1106 and 5 mg/kg of PK11195 by 80% and 70%, respectively. Specific binding was estimated as 80% of total binding. [(11)C]DAA1106 binding was four times higher compared to the binding of [(11)C]PK11195 in the monkey occipital cortex. These results indicated that [(11)C]DAA1106 might be a good ligand for in vivo imaging of PBR.

Acetamides↗

Corneal epithelial barrier function in diabetic patients.

PURPOSE: To evaluate the corneal epithelial barrier function in diabetic patients. METHODS: In 29 eyes of 29 diabetic patients and 55 eyes of 55 nondiabetic controls, corneal epithelial permeability to fluorescein was measured using an anterior fluorophotometer. The average fluorescein concentration in the central cornea was compared between diabetic patients and controls. Multiple regression analysis was used to assess the factors that affect corneal epithelial barrier function in diabetic patients. RESULTS: The average fluorescein concentrations in diabetic patients and nondiabetic controls were 44.1 +/- 25.3 ng/mL and 29.9 +/- 19.8 ng/mL (mean +/- SD), respectively (P = 0.0057, unpaired t test). An explanatory variable relevant to the impaired corneal epithelial barrier function was the serum hemoglobin A1c (HbA1c) concentration (standardized partial regression coefficient = 0.466, P = 0.0163). CONCLUSIONS: The corneal epithelial barrier function is impaired in diabetic patients. Diabetic patients with higher serum HbA1c levels are more predisposed to impaired barrier function in the corneal epithelium.

Aged↗

Monkey brain areas underlying remote-controlled operation.

We can control distant tools effectively by manipulating other objects as controllers in various remote-operated ways, even when the two mechanics are altered. To master the remote operation, we may rely on internal representation to organize individual moves of the controller and tool into a set of sequences by mapping the motor space among hand, controller and tool as a continuum. The present study confirmed that monkeys could also organize a sequence by mapping such a motor space or reorganize by remapping even after alteration. In addition, to investigate the neural substrates underlying such mapping/remapping, we measured the regional cerebral blood flow of two monkeys during joystick-controlled operation with alterable function of mechanics using positron emission tomography with. The monkeys were scanned during three different tasks produced by altering the directional gains of the x or y axis of the joystick - the two mechanics are congruent (standard task) and not congruent (reversed in the X or Y axis, X reverse or Y reverse task, respectively). Compared with random movement of the joystick as the control task, increased activities were detected in the prefrontal cortex, higher-ordered motor cortex, posterior parietal cortex and cerebellum during the standard task. Common brain areas during performance of the X reverse and Y reverse task were identified as showing almost the same pattern as during the standard task. These shared areas may not simply be associated with organization of individual motor imagery, but also with context-dependent processing of reorganization based on current functions by means of internal representation.

Animals↗

Fronto-parieto-cerebellar interaction associated with intermanual transfer of monkey tool-use learning.

Prior motor skill learning (original learning; OL) with one hand (original hand; OH) can affect relearning of the same skill (transfer learning; TL) with the opposite hand (transferred hand; TH). This phenomenon is known as intermanual transfer of learning. We explored specialization of brain activation underlying tool-use between hands by measuring regional cerebral blood flow in two monkeys using positron emission tomography. We found brain activation specified for TL in the bilateral prefrontal cortex, bilateral intraparietal sulcus region, and cerebellum contralateral to TH. The results suggest that those regions may be related to intermanual transfer of tool-use learning, presumably in terms of modifying a motor engram specific for OH.

Animals↗

Macaque prefrontal activity associated with extensive tool use.

Macaques can utilize tools sequentially on a single object or they can modify functions effectively in a relevant context. Two Japanese macaques were scanned by positron emission tomography with H(2)15O during a tool combination task and two control tasks (single tool task and simple stick-waving task). In the tool combination task, monkeys were required to use two identical tools properly in different functions. We found increased activity in the bilateral prefrontal cortex (area 9/46), bilateral intraparietal sulcus regions, right cerebellum, and bilateral early visual cortices during the tool combination task with the right hand, compared with the single tool task. These results suggest that interactions between the fronto-cerebellar and the fronto-parietal circuit are responsible for appropriate and effective modifications of tools in their functions.

Animals↗