Public transportation and the disabled person

機能訓練事業として実施している「生活リハビリ教室」の教室生208名を対象に，公共交通機関を利用して外出するために障害になっている要因を明らかにする目的で，郵送法による自記式アンケート調査を行った。回答は125名（60.1％）からあった。外出経験がある者は67名（53.6％）で外出経験がない者が58名であった。外出時に付添いが必要と思っている者は，外出経験のない者に多かった。公共交通機関を利用しての外出を阻害している要因には，乗り物の昇降口に段差があることや早く発車して危険である，また周囲の人に介助を依頼しにくいことなどが挙げられている。身体機能障害者が外出できない理由は個人によって異なってはいるが，地域社会に身体機能障害者を受け入れる環境を整えていく必要がある。A survey was distributed by mail to disabled people who received functional training in 1997. Of 208 questionnaires sent, 125 (60.1%) were returned. Sixty-seven (53.6%) of the respondents had experience traveled outside. People who participate in functional trainning for disability hope to have an attendant to accompany them when traveling. One primary factor that hinders traveling outside and using public transportation is that they cannot ask for help because of shyness. Another factor is the construction of entrances (e.g.,bumps) for vehicles which cannot be traversed easily. Reasons differed among those who had traveled outside and those who had not. It is necessary to prepare an environment (e.g., public transportationto) for ease of use for disabled persons in regional communities

Intratumoral heterogeneity and clonal evolution induced by HPV integration

The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines identified a previously undescribed form of structural variation, "heterocateny," characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer. Unique breakpoints shared across structural variants facilitated stepwise reconstruction of their evolution from a common molecular ancestor. This analysis revealed that virus and virus-host concatemers are unstable and, upon insertion into and excision from chromosomes, facilitate capture, amplification, and recombination of host DNA and chromosomal rearrangements. Evidence of heterocateny was detected in extrachromosomal and intrachromosomal DNA. These findings indicate that heterocateny is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intratumoral heterogeneity and clonal evolution

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in Japan

Background The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. Methods We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. Results The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. Conclusion The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex

Murine Leukemias with Retroviral Insertions at Lmo2 Are Predictive of the Leukemias Induced in SCID-X1 Patients Following Retroviral Gene Therapy

Five X-linked severe combined immunodeficiency patients (SCID-X1) successfully treated with autologous bone marrow stem cells infected ex vivo with an IL2RG-containing retrovirus subsequently developed T-cell leukemia and four contained insertional mutations at LMO2. Genetic evidence also suggests a role for IL2RG in tumor formation, although this remains controversial. Here, we show that the genes and signaling pathways deregulated in murine leukemias with retroviral insertions at Lmo2 are similar to those deregulated in human leukemias with high LMO2 expression and are highly predictive of the leukemias induced in SCID-X1 patients. We also provide additional evidence supporting the notion that IL2RG and LMO2 cooperate in leukemia induction but are not sufficient and require additional cooperating mutations. The highly concordant nature of the genetic events giving rise to mouse and human leukemias with mutations at Lmo2 are an encouraging sign to those wanting to use mice to model human cancer and may help in designing safer methods for retroviral gene therapy

Ultra-Rare Mutation in Long-Range Enhancer Predisposes to Thyroid Carcinoma with High Penetrance

Peer reviewe

Correlation between Ca2+ oscillation and cell proliferation via CCKB/gastrin receptor

AbstractGastrin stimulates cell proliferation through the CCKB receptor coupled to Gq-protein, whereas the m3 muscarinic receptor, which also couples to Gq, has no trophic effects. In order to elucidate the cause of the difference, we stably transfected CHO cells with human CCKB and m3 receptors. Stimulation of the CCKB, but not the m3 receptor increased cell growth. Activation of MAP kinase via the m3 receptor was to the same extent as that via CCKB, indicating that there is an initial signaling common to both receptors. Stimulation of either receptor induced a transient increase in [Ca2+]i followed by a sustained plateau phase. After 2 h of stimulation, the [Ca2+]i response to the m3 receptor disappeared, whereas that to the CCKB receptor remained as a [Ca2+]i oscillation. Removal of extracellular Ca2+, which abolished [Ca2+]i oscillation, completely inhibited DNA synthesis via CCKB. When the C-terminal part of the CCKB receptor was truncated, the trophic effect as well as the [Ca2+]i response after 2 h of stimulation disappeared, whereas the chimeric CCKB receptor with the C-terminal region of the m3 receptor preserved its ability to elicit both DNA synthesis and [Ca2+]i oscillation. These results suggest that desensitization might be a principal determinant of cell proliferation, and the persistence of the [Ca2+]i response as [Ca2+]i oscillation could be essential for this type of signal transduction