Legal Training and Front Line of Criminal Defense

平成30年11月4日（日）に，第12回広島大学ホームカミングデー企画（法科大学院講演会）「刑事弁護の最前線と法曹養成」として，東千田未来創生センターにおいて，弁護士（大阪弁護士会）の亀石倫子氏，弁護士（広島弁護士会）で元広島大学大学院法務研究科教授の久保豊年氏を講師に迎え，第1部では講演会を，第2部では本研究科の新井誠教授，堀田尚徳准教授が加わりパネルディスカッションを開催しました。 本稿は，当日のテープ録音をもとに，その概要を報告するものです。（なお，講演会とパネルディスカッションに引き続き行われた，フロアとの質疑応答については，紙幅の関係上，省略させていただきました。

Skeletal muscle function and vitamin D

Age-related changes in muscle strength and physical functions, and the association between vitamin D status and skeletal muscle functions were investigated in 36 men (21-90 years old) and 52 women (21-104 years old). Significant ageing-related decreases in several skeletal muscle functions and serum 25-hydroxyvitamin D [25(OH)D] levels were observed in both men and women. Cut-off values for the Timed up and go (TUG) test, walking speed, handgrip strength and Barthel Index (BI) detecting walking difficulties in the receiver operating characteristic (ROC) analysis were 11.1 sec, 0.60 m / sec, 17.0 kg, and 90.0 in males, and 28.6 sec, 0.43 m / sec, 13.9 kg, and 67.5 in females, respectively. By comparing personal present data of muscle strength with these cut-off values, people can easily understand their process to walking difficulty. Therefore, these results are important and useful to avoid or to delay a handicapped and dependent status by improving the vitamin D level, rehabilitation and nursing care

Skeletal muscle mass and vitamin D

A clearer understanding of skeletal muscle mass (SMM) in middle-aged and elderly individuals is important for maintaining functionality. In the present study, age-related changes in SMM, the threshold of SMM with walking difficulty, intestinal nutrient absorption rate, and various serum factors were examined in Japanese populations of different ages. We used 24-h creatinine excretion as a measure of total body SMM. Age-related decreases in SMM, intestinal nutrient absorption rates, and serum 25-hydroxyvitamin D [25(OH)D] concentrations were significantly higher in women than in men. The cut-off values for SMM (kg), its percentage of total body weight (BW), the SMM index [SMMI] (Kg / m2), and creatinine height index (CHI) (%) in elderly individuals with walking difficulty were approximately 8-10 kg, 17-20% of BW, 3.9-4.6 kg / m2, and 44%, respectively. Serum 25(OH)D concentrations were closely associated with SMM (kg, % of BW, kg / m2) and CHI (%) as well as the intestinal absorption rates of nitrogen (%) and phosphorus (%) in women, but not in men. The present results demonstrate that vitamin D is an important metabolic factor in skeletal muscle, and contributes to the optimal management of skeletal muscle and the prevention of sarcopenia

Chronic inhibition of the norepinephrine transporter in the brain participates in the seizure sensitization to cocaine and local anesthetics

Involvement of chronic inhibition of monoamine transporters (MAT) in the brain concerning the sensitization of cocaine- and local anesthetic-induced seizures was studied in mice. Repeated administration of subconvulsive doses of meprylcaine as well as cocaine, both of which inhibit MAT, but not lidocaine, which does not inhibit MAT, increased seizure activity and produced sensitization to other local anesthetics. Effects of 5 daily treatments of monoamine transporter inhibitors on lidocaine-induced convulsions were examined 2 or 3 days after the last dose of the inhibitors. The daily treatments of GBR 12935, a specific inhibitor of dopamine uptake, significantly increased the incidence and the intensity of lidocaine-induced convulsions at 20 mg/kg and decreased the threshold of the convulsions. The daily treatments of desipramine and maprotiline, selective norepinephrine uptake inhibitors, markedly increased the incidence and intensity of lidocaine-induced convulsions, and decreased the threshold with dose-dependent manner between 5 and 20 mg/kg. The daily treatments of citaloplam, a selective serotonin uptake inhibitor, 10 and 20 mg/kg, produced no significant increase in the incidence or intensity of lidocaine-induced convulsions but decreased the threshold of the convulsions. These results suggest that the chronic intermittent inhibition of monoamine uptake increases susceptibility to cocaine- and local anesthetic-induced seizures, and a norepinephrine transporter is an integral component of this sensitization

Intramuscular Adipose Tissue Content Predicts Patient Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

移植の成功に重要なのは、「質の良い」筋肉 --コンピュータ断層撮影を用いて評価した骨格筋指標での検討--. 京都大学プレスリリース. 2022-07-12.During clinical courses involving allogeneic hematopoietic stem cell transplantation (allo-HSCT), multidisciplinary assessments for patients including physical functions are indispensable, and quantitative skeletal muscle loss is a poor prognostic marker. In addition, deteriorating quality of muscle due to intra-muscle adipose tissue degeneration can be important as well, because many patients are cachexic or sarcopenic before allo-HSCT, although this approach has not been employed yet. Therefore, we conducted a retrospective cohort study to evaluate the quality, as well as quantity of skeletal muscle using computed tomography (CT). Psoas muscle mass index (PMI) and radiographic density (RD) calculated by cross-sectional area and averaged CT values of the psoas major muscle at the umbilical level were used to determine the quantity and quality of muscle, respectively. In total, 186 adult patients, aged 17-68 years (median, 49) were included in this study, and 46 (24.7%) and 49 (26.3%) patients were assigned to the lower PMI and RG groups. Low RD was identified as an independent risk factor for poor overall survival after allo-HSCT (adjusted hazard ratio 2.54, p<0.01), while PMI was not significant. Decreased RD along with reduced 6-min walking distance before transplantation was also significant factor for increased non-relapse mortality (hazard ratio, 2.69, p=0.01). This study is the first to suggest the use of a qualitative skeletal muscle index to serve as a prognostic indicator following allo-HSCT. RD should be included in pre-transplant screening parameters, and approaches that include rehabilitation focused on improving both muscle quality and quantity may improve the prognosis of allo-HSCT

Semiquantitative assessment of FDG uptake in primary tumours

Objective: To semiquantitatively estimate fluorine-18-fluorodeoxyglucose (FDG) uptake in primary lung cancer cells using dynamic and dual-time-point (DTP) positron emission tomography/computed tomography (PET/CT) to obtain a diagnostic index for lymph node (LN) metastasis. Methods: Forty-five patients with lung cancer underwent dynamic and DTP PET/CT examinations. All primary lesions and LN metastases were evaluated pathologically. At each time phase, we assessed the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the primary tumours. We investigated the relationship between semiquantitative index and the presence of LN metastasis for each case and for all cases satisfying indications for segmentectomy. In cases with LN metastasis, we assessed the SUVmax of pathologically proven metastatic LNs and non-metastatic LNs in each dynamic phase for evaluating temporal change. Results: Among 45 patients, 15 had 17 LN metastasis. SUVmax, MTV, and TLG of primary tumours at each time phase were significantly associated with LN metastasis (p < 0.05). In receiver operating characteristic analysis, dynamic second and third phases showed high diagnostic ability for LN metastasis. The temporal change in SUVmax in the dynamic phase between primary tumours and metastatic LNs were significantly different (p = 0.065). The temporal change in SUVmax was significantly lower in non-metastatic LNs than in primary tumours and metastatic LNs (p < 0.0001). Conclusions: Semiquantitative assessment of FDG uptake in dynamic second and third phases and the assessment of temporal changes in SUVmax on dynamic PET/CT scans were important predictors in diagnosing LN metastasis

Skeletal muscle mass of old Japanese women suffering from walking difficulty in nursing home

By using 24 hour urinary creatinine levels, skeletal muscle mass (kg), its rate (%) of body weight and creatinine height index (%) were determined in old Japanese women suffering from walking difficulty in nursing home and compare with those of young university students. Those of old subjects showed approximately 30- 50%, 36-44% and44-46% of young subjects, respectively. It is suggested that these values are important and useful biomarkers for the planning and the achievement of rehabilitation program for the maintaining and restoring skeletal muscle mass and for the careful support by registered care workers to aged persons

Higher exercise tolerance early after allogeneic hematopoietic stem cell transplantation is the predictive marker for higher probability of later social reintegration

同種造血幹細胞移植後における社会復帰の予測因子を発見 --移植後リハビリテーションがもつ重要性--. 京都大学プレスリリース. 2021-04-09.As the proportion of long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is on the rise, it is essential to consider the significance of quality of life (QOL), including reintegration with society (returning to school or work). This retrospective cohort study aims to illustrate the precise epidemiology of social reintegration later after allo-HSCT and determine its predictive indicators. We enrolled 56 patients, and 40 patients (71%) attained social reintegration at 2 years post-HSCT. Reintegration failure markedly correlated with an inferior performance status and concurrent chronic graft-versus-host disease. In non-reintegrated patients, the physical function at discharge measured by the 6-min walking distance (6MWD) was markedly decreased. On the multivariate risk analyses, sex (female; odds ratio (OR) 0.07; 95% confidence interval (CI) 0.01–0.54; p = 0.01), HCT-CI (≥ 2; OR 0.10; 95% CI 0.01–0.84; p = 0.03), and change in 6MWD (per 5% increase; OR 1.47; 95% CI 1.01–2.13; p = 0.04) were significant predictors of later social reintegration. This study suggests that a multidisciplinary strategy including rehabilitation is essential, especially in patients with poor predictive markers at an early phase, and we should consider suitable rehabilitation programs to prevent a decline in exercise tolerance and improve social reintegration and overall QOL in patients after allo-HSCT

The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene

The major physiological activity of 1,25-hydroxyvitamin D3 (1,25(OH)2D3) is the regulation of calcium absorption in the small intestine, and the level of vitamin D receptor (VDR) is an important factor in this regulation. In a previous study, we demonstrated that the caudal-related homeodomain Cdx-2 played an important role in the intestine-specific transcription of the human VDR gene. In the present study, the polymorphism was identified in the core sequence 5'-ATAAAAACTTAT-3' in the Cdx-2 binding site in the VDR gene promoter. In 261 Japanese women with genotyped VDR polymorphisms, 48 were genotype Cdx-A (adenine at-3731 nt relative to the transcription start site of human VDR gene, 5'-A_TAAAAACTTAT'-3'), 82 were genotype Cdx-G (guanine at-3731 nt, 5'-G_TAAAAACTTAT-3'), 131 were genotype Cdx-A/G (heterozygote). The bone mineral density (BMD) in the lumbar spine (L2-4) with the Cdx-A homozygote was 12% lower than that with the Cdx-G homozygote (P<0.05). In electropholertic gel mobility shift assay, the oligonucleotide with Cdx-G allele markedly decreased the binding to Cdx-2 compared with that in the Cdx-A allele. The transcriptional activity of the VDR promoter with Cdx-G allele was decreased to 70% of the Cdx-A allele. In addition, in the herpes simplex virus thymidine kinase promoter, the Cdx-2 binding element with the G allele showed significantly lower transcriptional activity than that of the A allele. Thus, the polymorphism in the Cdx-2 binding site of the VDR gene (Cdx-polymorphism) would affect the expression of VDR in the small intestine. In addition, this polymorphism may modulate BMD in postmenopausal Japanese women