大学院医学系研究科（医学）

Abstract Purpose: The purpose of this study was to investigate the effects of two different postures (sitting and standing) and three different ambient temperatures (10℃, 20℃, and 30℃) on heart rate variability (HRV) among healthy young adults. Methods: Twelve young adult volunteers (males 6, females 6) were recruited. Following acclimatization to any the room temperature (10℃, 20℃ or 30℃), 5-min measurements of HRV were conducted in sitting and standing postures of the subjects. Results: Compared to the sitting posture, measurements obtained in the standing posture revealed a significant decrease in high-frequency power/HF, root mean square of successive differences between RR intervals, standard deviation of Poincaré plot perpendicular to the line-of-identity or SD1 and SD1/standard deviation of Poincaré plot along the line-of-identity or SD2, and a significant increase in lowfrequency power/LF and LF/HF under all experimental conditions (p<0.05 to 0.005). Majority of HRV parameters showed significant differences while the values obtained under 10℃ were compared with 20℃ and 30℃ conditions, respectively (p<0.05 to 0.001). Conclusions: Our findings suggest the predominance of sympathetic tone in the standing compared with sitting posture. Furthermore, colder conditions caused a predominance of the parasympathetic activity in both sitting and standing postures, and such effects of ambient temperature on the sympathovagal balance were stronger in the latter posture.

Abstract Objectives: This study examined the short-term outcomes of endovascular therapy (EVT) with the GORE VIABAHN VBX (VBX) which is a balloon-expandable covered stent in patients with aortoiliac occlusive disease (AIOD) and acute limb ischemia (ALI). Methods: This was a single-center retrospective review of patients with AIOD and ALI who underwent EVT with the VBX between December 2018 and January 2021. Primary, assisted, and secondary patency rates were assessed, along with 30-day mortality rates. Results: Twenty-two patients underwent EVT with the VBX; 18 patients had AIOD, whereas 4 had ALI. The incidence of TransAtlantic Intersociety Classification II D lesions was 50% (n=9). Technical success was 100%. One patient with unilateral common iliac artery stenosis developed an intraoperative dissection of the distal edge of the VBX, which required an additional self-expanding VIABAHN stent on the distal edge of the VBX. The primary patency rate at 24 months was 100%. No patients required additional target vessel treatment at a median follow-up of 10 months (range, 1-27). EVT was also successful in the four patients with ALI, who had no complications of the target vessel. Conclusion: The present study demonstrated that EVT with the VBX is effective for AIOD and ALI.

Incontinentia pigmenti (IP; OMIM# 308300) is a rare inherited disease caused by a mutation of IKBKG, which is also known as NEMO, located on Xq28. IP patients usually present with abnormalities of skin, eyes, nails and central nervous system. The neurological damege, which occur usually from neonatal through the early infantile period, leads to neulogical complication such as development retardation, motor paralysis and epilepsy. However, there has been little study done concerning the effect of therapy for the neural abnormalities. We have investigated the clinical findings in a female IP case with a novel mutation of IKBKG for six years due to disclosing the neurological prognosis and the immunological features. It is hoped that the present study will contribute to a better management of IP patients.

The hippocampal dentate gyrus has been identified to play a critical role in maintaining contextual memory in many mammalian species. To evaluate learninginduced synaptic plasticity of granule cells, we subjected male rats to an inhibitory avoidance (IA) task and prepared acute hippocampal slices. In the presence of 0.5 μM tetrodotoxin, we recorded miniature excitatory post synaptic currents (mEPSCs) and inhibitory post synaptic currents (mIPSCs) in male rats experiencing four groups: untrained, IA-trained, unpaired, and walk-through. Compared with the untrained, IA-trained, unpaired, and walk-through groups, the unpaired group significantly enhanced mean mEPSC amplitudes, suggesting the experience-induced plasticity at AMPA receptor-mediated excitatory synapses. For inhibitory synapses, both unpaired and walk-through groups significantly decreased mean mIPSC amplitudes, showing the experience-induced reduction of postsynaptic GABAA receptor-mediated currents. Unlike the plasticity at CA1 synapses, it was difficult to explain the learning- specific plasticity at the synapses. However, overall multivariate analysis using four variables of mE(I)PSC responses revealed experience-specific changes in the diversity, suggesting that the diversity of excitatory/inhibitory synapses onto granule cells differs among the past experience of animals include the learning. In comparison with CA1 pyramidal neurons, granule cells consistently showed greater amplitude and frequency of mE(I)PSCs. Fluctuation analysis further revealed that granule cells provide more postsynaptic AMPA receptor channels and greater single-channel current of GABAA receptors of than CA1 pyramidal neurons. These findings show functional differences between two types of principal cells in the hippocampus.

Androgen receptor (AR)-signaling plays an important role in promoting tumor cell survival and the development of castration-resistant prostate cancer (CRPC). Androgen deprivation therapy is the basic therapeutic strategy for AR signaling blockade, but that effects wonʼt last long and most of metastatic prostate cancer show castration resistance. Recently, new agents, AR Axis Targeted agents (ARAT), have been developed. We have been developing our bench-to-bedside translational research to elucidate the mechanisms of drug resistance in prostate cancer. This review describes our investigational results and recent advances in CRPC with ARAT treatment strategy.