A Sustainable Consciousness Promoting Dialogue With Alien Others: Bakhtin’s Views on Laughter and Euripides’ Tragi-comedy

Today, people live in a culturally diverse world and often face criticisms of their ideas by outsiders who have alien perspectives. Russian literary researcher M. M. Bakhtin valued such criticisms, which may bring forth unprecedented perspectives that bridge gaps between different viewpoints. In this paper, I investigate Bakhtin’s notions concerning ‘laughter’, which describe the mental functions involved in productive dialogue. Greek tragic dramatist Euripides is the main figure of my analysis as an influence on Bakhtin’s notions of the value of laughter and dialogue, although Bakhtin did not employ systemic citations of Euripides’ works. I focus on speaker consciousness, which is described as occurring when negotiating with others who have alien viewpoints in Greek tragedies. I then propose sustainable models of consciousness that may promote communication in current contexts of ideological diversity

Genome-Wide Expression of Azoospermia Testes Demonstrates a Specific Profile and Implicates ART3 in Genetic Susceptibility

Infertility affects about one in six couples attempting pregnancy, with the man responsible in approximately half of the cases. Because the pathophysiology underlying azoospermia is not elucidated, most male infertility is diagnosed as idiopathic. Genome-wide gene expression analyses with microarray on testis specimens from 47 non-obstructive azoospermia (NOA) and 11 obstructive azoospermia (OA) patients were performed, and 2,611 transcripts that preferentially included genes relevant to gametogenesis and reproduction according to Gene Ontology classification were found to be differentially expressed. Using a set of 945 of the 2,611 transcripts without missing data, NOA was further categorized into three classes using the non-negative matrix factorization method. Two of the three subclasses were different from the OA group in Johnsen's score, FSH level, and/or LH level, while there were no significant differences between the other subclass and the OA group. In addition, the 52 genes showing high statistical difference between NOA subclasses (p < 0.01 with Tukey's post hoc test) were subjected to allelic association analyses to identify genetic susceptibilities. After two rounds of screening, SNPs of the ADP-ribosyltransferase 3 gene (ART3) were associated with NOA with highest significance with ART3-SNP25 (rs6836703; p = 0.0025) in 442 NOA patients and 475 fertile men. Haplotypes with five SNPs were constructed, and the most common haplotype was found to be under-represented in patients (NOA 26.6% versus control 35.3%, p = 0.000073). Individuals having the most common haplotype showed an elevated level of testosterone, suggesting a protective effect of the haplotype on spermatogenesis. Thus, genome-wide gene expression analyses were used to identify genes involved in the pathogenesis of NOA, and ART3 was subsequently identified as a susceptibility gene for NOA. These findings clarify the molecular pathophysiology of NOA and suggest a novel therapeutic target in the treatment of NOA

前立腺癌に対するPepleomycin(Bleomycin Derivative, NK-631)の効果

未治療の前立腺腺癌2症例に本剤を投与し，その効果を検討した。症例1： 71歳， 排尿困難，左大腿部痛を主訴として1978年6月15日当科受診。前立腺は超鶏卵大，石様硬，表面不整，骨盤へ浸潤。左ソケイ部にくるみ大の硬いリンパ腺を触知。骨シンチで多数の転移を認めた。 前立腺の針生検組織像は分化型腺癌であった。pepleomycin 200 mg (1回10mg，静注， 週3回)の投与により前立腺癌，左ソケイ部リンパ腺の著明な縮小がみられ，血清酸ホスファターゼ値が治療前6.5K.A.U.から9.5K.A.U まで低下した。治療終了後の生検組織像は癌細胞の変性，壊死組織の線維化が目立った。　　症例2: 74歳，排尿困難で1978年8月19日当科受診。前立腺は鶏卵大，硬，周囲に浸潤。骨シンチで転移巣が多数あり，前立腺生検組織像は未分化型腺癌であった。 pepleomycin投与で自覚症状は症例1ほどの改善はみられず，前立腺癌そのものもあまり縮小しなかったが，残尿は80mlから10mlへ減少した。治療後の前立腺生検所見でも癌細胞の空胞化が著明に認められた。なお副作用としては症例1では著明な皮膚変化がみられたが，症例2でぎ軽度の口内炎を認めるにとどまった。NK 631 投与前後で血中FSH，LH，testosteroneを測定したところ，両症例ともに投与終了後FSH，LH，t estosterone値は投与前値の約1/2となっていた (Table 2)。 つまり， NK 631 の抗腫瘍作用はDNA合成抑制によるということになっているが，前立腺癌に対する抗腫聖書効果はNK631 の下重体抑制による睾丸のLeydig cellよりのandrogen分泌抑制も関与している可能性があることが示唆された。本剤の下垂体抑制効果については今後検討されるべき課題であると考える。Since the new bleomycin derivative-pepleomycin was reported to be effective for experimentally induced adenocarcinoma of stomach in rats, it was administered in two cases of prostatic cancer. Satisfactory response was obtained in well differentiated carcinoma, meanwhile only histological effect was observed in undifferentiated one. It seems that the effect of pepleomycin on prostatic cancer was brought about by the suppression of DNA synthesis of tumor and also of pituitary function resulting in decreased androgen secretion from Leydig cells

Gene expression in a canine basilar artery vasospasm model: a genome-wide network-based analysis

To investigate the changes of gene expression on the cerebral vasospasm after subarachnoid hemorrhage, we used genome-wide microarray for a canine double-hemorrhage model and analyzed the data by using a network-based analysis. Six dogs were assigned to two groups of three animals: control and hemorrhage. The effects were assessed by the changes in gene expressions in the artery 7 days after the first blood injection. Among 23,914 genes, 447 and 66 genes were up-regulated more than two- and fivefold, respectively, and 332 and 25 genes were down-regulated more than two- and fivefold, respectively. According to gene ontology, genes related to cell communication (P = 5.28E-10), host–pathogen interaction (7.65E-8), and defense–immunity protein activity (0.000183) were significantly overrepresented. The top high-level function for the merged network derived from the network-based analysis was cell signaling, revealing that the subgroup that regulates the quantity of Ca2+ to have the strongest association significance (P = 4.75E-16). Canine microarray analysis followed by gene ontology profiling and connectivity analysis identified several functional groups and individual genes responding to cerebral vasospasm. Ca2+ regulation may play a key role in these gene expression changes and may be involved in the pathogenesis of cerebral vasospasm

悪魔学書『魔女への鉄槌』の総合的研究 [全文の要約]

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Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis

Background: The results of meta-analyses conducted by previous association studies between total homocysteine and schizophrenia suggest that an elevated total homocysteine level is a risk factor for schizophrenia. However, observational studies have potential limitations, such as confounding and reverse causation. In the present study, we evaluated a causal relationship between plasma total homocysteine and schizophrenia by conducting a Mendelian randomization analysis. Methods: We used the MTHFR C677T polymorphism as an instrumental variable, which affects the plasma total homocysteine levels. To calculate the risk estimate for the association of this single nucleotide polymorphism (SNP) with schizophrenia, we conducted a meta-analysis of case–control studies that comprise a total of 11,042 patients with schizophrenia and 14,557 control subjects. We obtained an estimate for the association of this SNP with the plasma total homocysteine levels from a meta-analysis of genome-wide association studies comprising 44,147 individuals. Results: By combining these two estimates, we demonstrated a significant effect of the plasma total homocysteine on schizophrenia risk, representing an OR of 2.15 (95 % CI = 1.39–3.32; p = 5.3 x 10−4) for schizophrenia per 1-SD increase in the natural log-transformed plasma total homocysteine levels. Conclusions: We provided evidence of a causal relationship between the plasma total homocysteine and schizophrenia, and this result will add insight into the pathology and treatment of schizophrenia

悪魔学書『魔女への鉄槌』の総合的研究 [論文要旨及び審査の要旨]

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