A Novel Method for Efficient Collection of Normal Mesothelial Cells In Vivo

Asbestos-induced mesothelioma is a challenging social problem in many countries, and oxidative stress via iron is closely associated with its carcinogenesis. Mesothelioma is thought to originate from the mesothelial cells that cover the somatic cavity such as pleural, pericardial and peritoneal cavities. They are single layered and so flat that it is extremely difficult to obtain pure mesothelial cells as control samples from experimental animals. Here we describe a novel method to collect mesothelial cells from animals by the use of simple equipments. Surface of the most organs including lung, spleen and liver are covered with a single layer of mesothelial cells. Scraping the surface of those organs with razor blades after snap-freeze in liquid nitrogen satisfactorily confers almost pure population of mesothelial cells. This simple method would be helpful for obtaining mesothelial control samples from animals to elucidate the molecular mechanisms of a variety of mesothelial pathology

Age- and sun exposure-dependent differences in 8-hydroxy-2'-deoxyguanosine and Nε-(carboxymethyl)lysine in human epidermis

Aging and exposure to sunlight are two major factors in the deterioration of skin function. In this study, thirty-six fixed human skin samples from sun-exposed and unexposed areas from young and old individuals were used to evaluate the localization of oxidative stress according to levels and distribution of 8-hydroxy-2'-deoxyguanosine and Nε-(carboxymethyl)lysine in samples using immunohistochemistry. In the epidermis of the young, negligible amounts of 8-hydroxy-2'-deoxyguanosine and Nε-(carboxymethyl)lysine were detected in unexposed areas, whereas nuclear 8-hydroxy-2'-deoxyguanosine and cytoplasmic Nε-(carboxymethyl)lysine were increased in the lower epidermis in sun-exposed areas. In contrast, the aged presented prominent nuclear 8-hydroxy-2'-deoxyguanosine and nuclear Nε-(carboxymethyl)lysine in the epidermis of unexposed areas, concomitant with dermal increase in Nε-(carboxymethyl)lysine. However, the immunostaining of 8-hydroxy-2'-deoxyguanosine and Nε-(carboxymethyl)lysine revealed a decrease in the epidermis of sun-exposed areas in the aged. These results suggest an age-dependent difference in the adaptation and protective mechanisms of the epidermis against sunlight-associated oxidative stress, thus necessitating distinct standards for evaluation in each age group. Further investigation is warranted to elucidate underlying molecular mechanisms

Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people

Objectives: Increased attention is being paid to Asian medicine in balanced total health care. We investigated the effects of mixed exercise including yoga ('Yoga-plus') among elderly individuals. Methods: A total of 385 subjects (72 males and 313 females, 75.5 ± 8.7 years old) participated in a 12-month (M) exercise program at a health and welfare center, a day service center, and a nursing home. Cognitive, affective, and physical functions, and activities of daily living (ADL), were compared at baseline (0M), 6M and 12M of exercise intervention. Results: Mean scores on the frontal assessment battery, clock drawing test, cube copying test, letter fluency, and category fluency significantly improved after the Yoga-plus intervention, while mini-mental state examination, Hasegawa dementia score-revised, and trail-making test performance were relatively stable. Affective scores on the geriatric depression scale (GDS), apathy scale (AS) and Abe's behavioral and psychological symptoms of dementia were not significantly affected by exercise therapy, but subgroups with higher baseline GDS (GDS ≥ 5) and AS (AS ≥ 16) scores showed a significant improvement after intervention. One-leg standing time and 3-m timed up and go test performance significantly improved after 12M intervention. Discussion: Yoga-plus improved cognitive, affective, ADL, and physical functions in a local elderly population, particularly among below-baseline individuals, indicating the benefits of dementia prevention among elderly individuals

Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase

AbstractThe Epstein-Barr virus (EBV) BGLF4 gene product is the only protein kinase encoded by the virus genome. In order to elucidate its physiological roles in viral productive replication, we here established a BGLF4-knockout mutant and a revertant virus. While the levels of viral DNA replication of the deficient mutant were equivalent to those of the wild-type and the revertant, virus production was significantly impaired. Expression of the BGLF4 protein in trans fully complemented the low yield of the mutant virus, while expression of a kinase-dead (K102I) form of the protein failed to restore the virus titer. These results demonstrate that BGLF4 plays a significant role in production of infectious viruses and that the kinase activity is crucial

Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis

In sudden unexpected death in infancy cases, postmortem genetic analysis with next-generation sequencing potentially can extract candidate genes associated with sudden death. However, it is difficult to accurately interpret the clinically significant genetic variants. The study aim was to conduct trio analysis of cases of sudden unexpected death in infancy and their parents to more accurately interpret the clinically significant disease-associated gene variants associated with cause of death. From the TruSight One panel targeting 4813 genes we extracted candidate genetic variants of 66 arrhythmia-, 63 inherited metabolic disease-, 81 mitochondrial disease-, and 6 salt-losing tubulopathy-related genes in 7 cases and determined if they were de novo or parental-derived variants. Thirty-four parental-derived variants and no de novo variants were found, but none appeared to be related to the cause of death. Using trio analysis and an in silico algorithm to analyze all 4813 genes, we identified OBSCN of compound heterozygous and HCCS of hemizygous variants as new candidate genetic variants related to cause of death. Genetic analysis of these deceased infants and their living parents can provide more accurate interpretation of the clinically significant genetic variants than previously possible and help confirm the cause of death

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

An Empirical Study Of Variation In The Use Of Honorific Forms In Japanese: An Analysis Of Forms Produced By A Group Of Women In An Urban Setting.

This is an empirical study of variation in the actual use of Japanese honorific speech forms by a network of female speakers in Setagaya ward, a middle to upper-middle class residential area of Tokyo. To the best of my knowledge, it is the first study of Japanese honorifics to offer a quantitative delineation of the relative importance of the social variables as factors which govern choice. The Cedergren-Sankoff variable rule program was used in the analysis of the data to find the relative constraining effect of age, status, role, sex, and solidarity on the choice of the respect forms; and to provide evidence of an apparent functional shift in the use of the nominal respect form kata. The present study examines honorific forms in a corpus of recorded speech. The subject sample was self-recruited, and was composed of six speakers, who belong to the same socioeconomic class, and age group (i.e., all but one in their mid-forties). The data were collected over a five-month period and consist of 19 45-minute lunch conversations and one 90-minute tea-time conversation. Two token samples were analyzed; one sample contains the neutral and respect alternatives of selected verbs (iru/irassharu 'to be,' iu/ossharu 'to say,' suru/nasaru 'to do,' V-te iru/irassharu resultative, repetitive, or continuative action); and the other the neutral and respect alternatives of a selected nominal form (hito/kata 'person, people'). All five social variables: solidarity, role, status, sex, and relative age, are found to be significant, and ranked in that order of importance as constraints governing the use of respect forms. The results provide quantitative support for the heretofore impressionistic observation, made by scholars, of the rising importance of solidarity as a factor governing choice of honorific form, and the concomitant decline in the importance of social status. In addition, the reduction in the number of social variables governing the use of the nominal respect form kata, and the contrasting patterns observed in the use of the respect and neutral forms of the verbs with that of the respect and neutral nominal forms kata and hito, provide empirical evidence in support of the notion that kata is losing its function as a respect form and is in the process of assuming the function of a beautificative (bikago) form.Ph.D.Language, Literature and LinguisticsLinguisticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/127649/2/8324314.pd

抗がん治療における抗体薬の価値最大化に向けた研究

京都大学0048新制・論文博士博士(農学)乙第12879号論農博第2806号新制||農||1028(附属図書館)学位論文||H26||N4878(農学部図書室)31597(主査)教授 植田 和光, 教授 植田 充美, 教授 矢﨑 一史学位規則第4条第2項該当Doctor of Agricultural ScienceKyoto UniversityDFA