Anesthetic Management with Propofol in a Patient with Rasmussen's Encephalitis Complicated by Intractable Partial-Onset Epileptic Seizures: A Case Report.

Introduction: Rasmussen's encephalitis (RE) is a progressive and chronic ailment characterized by drug-resistant epileptic seizures. RE is uncommon, and no documented accounts of its anesthetic management exist. Anesthetic management without causing epileptic seizures is important in RE. Here, we present a case of safe anesthetic management in a pediatric patient with RE. Case Presentation: A 7-year-old boy who was diagnosed with RE at the age of 6 years was scheduled for supernumerary tooth extraction under general anesthesia. The patient was being treated with prednisolone, sodium valproate, zonisamide, lacosamide, and famotidine. Despite receiving antiepileptic therapy, the patient experienced partial epileptic seizures several times per week. The seizures presented as numbness in his right hand and progressed to tonic-clonic seizures affecting the right side of his body. On the day of the surgical procedure, the patient was administered regular doses of antiepileptic drugs and prednisolone. Anesthesia was induced and maintained using a combination of propofol, remifentanil, and rocuronium. The surgical procedure was successfully performed, and the patient awakened smoothly from anesthesia. No epileptic seizures were observed intra- or postoperatively. Conclusion: RE typically presents with drug-resistant seizures and the initial symptoms are usually refractory partial seizures. Propofol is well-established as a treatment option for refractory status epilepticus, and it reduces the frequency of spikes in patients with partial epilepsy. In this case, general anesthesia without epileptic seizures was achieved using propofol.

Self-organization, quality control, and preclinical studies of human iPSC-derived retinal sheets for tissue-transplantation therapy.

Three-dimensional retinal organoids (3D-retinas) are a promising graft source for transplantation therapy. We previously developed self-organizing culture for 3D-retina generation from human pluripotent stem cells (hPSCs). Here we present a quality control method and preclinical studies for tissue-sheet transplantation. Self-organizing hPSCs differentiated into both retinal and off-target tissues. Gene expression analyses identified the major off-target tissues as eye-related, cortex-like, and spinal cord-like tissues. For quality control, we developed a qPCR-based test in which each hPSC-derived neuroepithelium was dissected into two tissue-sheets: inner-central sheet for transplantation and outer-peripheral sheet for qPCR to ensure retinal tissue selection. During qPCR, tissue-sheets were stored for 3-4 days using a newly developed preservation method. In a rat tumorigenicity study, no transplant-related adverse events were observed. In retinal degeneration model rats, retinal transplants differentiated into mature photoreceptors and exhibited light responses in electrophysiology assays. These results demonstrate our rationale toward self-organizing retinal sheet transplantation therapy.

Critical roles of interactions among switch I-preceding residues and between switch II and its neighboring alpha-helix in conformational dynamics of the GTP-bound Ras family small GTPases.

GTP-bound forms of Ras family small GTPases exhibit dynamic equilibrium between two interconverting conformations, "inactive" state 1 and "active" state 2. A great variation exists in their state distribution; H-Ras mainly adopts state 2, whereas M-Ras predominantly adopts state 1. Our previous studies based on comparison of crystal structures representing state 1 and state 2 revealed the importance of the hydrogen-bonding interactions of two flexible effector-interacting regions, switch I and switch II, with the γ-phosphate of GTP in establishing state 2 conformation. However, failure to obtain both state structures from a single protein hampered further analysis of state transition mechanisms. Here, we succeed in solving two crystal structures corresponding to state 1 and state 2 from a single Ras polypeptide, M-RasD41E, carrying an H-Ras-type substitution in residue 41, immediately preceding switch I, in complex with guanosine 5'-(ß,γ-imido)triphosphate. Comparison among the two structures and other state 1 and state 2 structures of H-Ras/M-Ras reveal two new structural features playing critical roles in state dynamics; interaction of residues 31/41 (H-Ras/M-Ras) with residues 29/39 and 30/40, which induces a conformational change of switch I favoring its interaction with the γ-phosphate, and the hydrogen-bonding interaction of switch II with its neighboring α-helix, α3-helix, which induces a conformational change of switch II favoring its interaction with the γ-phosphate. The importance of the latter interaction is proved by mutational analyses of the residues involved in hydrogen bonding. These results define the two novel functional regions playing critical roles during state transition.