Many neurons in the adult rat cingulate cortex possess perineuronal sulfated proteoglycans detectable with cationic iron colloid and aldehyde fuchsin, or cell surface glycoproteins reactive to lectin Vicia villosa or soybean agglutinin. The perineuronal sulfated proteoglycans develop three to four weeks after birth. The cell surface glycoproteins develop at earlier stage or two to three weeks after birth. Dark or active neurons begin to appear three to four weeks after birth. These findings indicate that the brain matures after birth or during weaning period.
en-copyright= kn-copyright= en-aut-name=TsubouchiMari en-aut-sei=Tsubouchi en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsubochiYutaka en-aut-sei=Tsubochi en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HitomiSayoko en-aut-sei=Hitomi en-aut-mei=Sayoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MurakamiTakuro en-aut-sei=Murakami en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama Univeristy affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University en-keyword=rat brain kn-keyword=rat brain en-keyword=perineuronal sulfated proteoglycans kn-keyword=perineuronal sulfated proteoglycans en-keyword=cell surface glycoproteins kn-keyword=cell surface glycoproteins en-keyword=dark neurons kn-keyword=dark neurons END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=6 article-no= start-page=305 end-page=311 dt-received= dt-revised= dt-accepted= dt-pub-year=1996 dt-pub=199612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cathepsin B in the Growth of Colorectal Cancer: Increased Activity of Cathepsin B in Human Colorectal Cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cathepsin B, a thiol protease, is involved in cancer metastasis. To clarify the role of cathepsin B in tumor progression in human colorectal cancer, the relationship between its activity, immunohistochemical staining, and clinical tumor progression was investigated. Cathepsin B activity in adenocarcinomas was significantly elevated compared with that in the tumor-bearing tissue. Furthermore, the tumor/tumor-bearing tissue (T/Tb) ratio of the activity was significantly higher than that of colorectal adenoma. Immunohistochemical studies demonstrated intense staining in the cancerous tissue. With respect to the clinical stage of tumors, the activity tended to be higher in tumors that had invaded the serosa or subserosa than in those that invaded the proper muscle. The results suggest that cathepsin B participates in the progression of human colorectal cancer, and its increased expression is a sensitive marker of the differentiation between colorectal adenoma and adenocarcinoma.
en-copyright= kn-copyright= en-aut-name=SatohYasumasa en-aut-sei=Satoh en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HigashiToshihiro en-aut-sei=Higashi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiotaTetsuya en-aut-sei=Shiota en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinugasaNobuyuki en-aut-sei=Kinugasa en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaKeigo en-aut-sei=Yoshida en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UematsuShuji en-aut-sei=Uematsu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakatsukasaHarushige en-aut-sei=Nakatsukasa en-aut-mei=Harushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimuraYukio en-aut-sei=Nishimura en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujiTakao en-aut-sei=Tsuji en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama Univeristy affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University affil-num=7 en-affil= kn-affil=Okayama University affil-num=8 en-affil= kn-affil=Okayama Univresity affil-num=9 en-affil= kn-affil=Kyushu University affil-num=10 en-affil= kn-affil=Okayama University en-keyword=cathepsin B kn-keyword=cathepsin B en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=colorectal adenoma kn-keyword=colorectal adenoma END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=6 article-no= start-page=285 end-page=292 dt-received= dt-revised= dt-accepted= dt-pub-year=1996 dt-pub=199612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Continuous Measurement of Tissue Oxygen and Carbon Dioxide Gas Tensions in Dog Liver in Ischemia/Reperfusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=An experiment was conducted to determine whether the oxygen and carbon dioxide gas tensions in liver tissue (PtO2 and PtCO2, respectively) reflect the state of microcirculation and/or metabolism in the ischemic liver. Subjects were divided into three groups: group 1, 30 min ischemia; group 2, 60 min ischemia; group 3, four times of intermittent 15 min ischemia after every 10 min of reperfusion. PtO2, PtCO2 and tissue blood flow (TBF) were measured by mass spectrometry, comparatively studied with the serum GOT level as an indicator of liver tissue damage. Furthermore, the time point at which the PtCO2 increase for 1 min initially became less than 1/2 of the maximum value was located on the transit curve of PtCO2, referred to as the critically anaerobic (CA) point, with which new indices of critically anaerobic score (CAS) and time (CAT) (see details in text) were developed. The profiles of PtO2 and PtCO2 during ischemia and reperfusion were clearly demonstrated, and the CA point was observed 12.7 +/- 2.9 min after induction of ischemia. PtO2 was positively correlated with TBF and negatively with the serum GOT level. Furthermore, not only CAS but also CAT were significantly correlated with PtO2, TBF, and the serum GOT level. It was concluded that PtCO2 reflects the state of anaerobic tissue metabolism during ischemia and PtO2 reflects the magnitude of microcirculatory disturbance and tissue injury caused by ischemia/reperfusion. Therefore, continuous monitoring of not only PtO2 but also PtCO2 is beneficial for patients undergoing hepatic surgery with ischemia. en-copyright= kn-copyright= en-aut-name=UrakamiAtsushi en-aut-sei=Urakami en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiraiRyuji en-aut-sei=Hirai en-aut-mei=Ryuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OtaTetsuya en-aut-sei=Ota en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SogaHiroyuki en-aut-sei=Soga en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NawaSugato en-aut-sei=Nawa en-aut-mei=Sugato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimizuNobuyoshi en-aut-sei=Shimizu en-aut-mei=Nobuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Second Department of Surgery, Okayama University Medical School affil-num=2 en-affil= kn-affil=Second Department of Surgery, Okayama University Medical School affil-num=3 en-affil= kn-affil=Second Department of Surgery, Okayama University Medical School affil-num=4 en-affil= kn-affil=Second Department of Surgery, Okayama University Medical School affil-num=5 en-affil= kn-affil=Second Department of Surgery, Okayama University Medical School affil-num=6 en-affil= kn-affil=Second Department of Surgery, Okayama University Medical School en-keyword=liver kn-keyword=liver en-keyword=ischemia kn-keyword=ischemia en-keyword=oxygen kn-keyword=oxygen en-keyword=carbon dioxide kn-keyword=carbon dioxide en-keyword=mass spectrometry kn-keyword=mass spectrometry END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=6 article-no= start-page=305 end-page=311 dt-received= dt-revised= dt-accepted= dt-pub-year=1996 dt-pub=199612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cathepsin B in the Growth of Colorectal Cancer: Suppressive Effect of Leupeptin on the Growth of DMH-Induced Rat Colon Neoplasm en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cathepsin B, a thiol protease, has been reported to be involved in cancer progression and metastasis. The suppressive effects of two kinds of protease inhibitors, leupeptin and dietary camostate (FOY-305), on tumorigenesis and progression in 1, 2-dimethylhydrazine (DMH)-induced rat colon neoplasm were examined in relation to tissue cathepsin B activity. Male Donryu rats were treated with leupeptin or FOY-305 during or after the administration of DMH. There were no significant differences in average tumor numbers among all DMH-treated groups. However, the percentage of small tumors was significantly higher in the group in which leupeptin was supplied during DMH administration. This trend was not recognized in the FOY-305-treated groups. The ratio of cathepsin B activity in the tumors to that in the tumor-bearing tissue (T/Tb) was significantly increased with increasing tumor size (P = 0.009). The cathepsin B activity levels in the tumor-bearing mucosa in the groups which received leupeptin or FOY-305 following DMH treatment were both significantly lower than that in the group which received neither protease inhibitor (P = 0.046 and P = 0.0067, respectively). The results obtained indicate that leupeptin may have suppressed tumor growth by lowering the tissue cathepsin B activity.
en-copyright= kn-copyright= en-aut-name=SatohYasumasa en-aut-sei=Satoh en-aut-mei=Yasumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HigashiToshihiro en-aut-sei=Higashi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ShiotaTetsuya en-aut-sei=Shiota en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KinugasaNobuyuki en-aut-sei=Kinugasa en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshidaKeigo en-aut-sei=Yoshida en-aut-mei=Keigo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=UematsuShuji en-aut-sei=Uematsu en-aut-mei=Shuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakatsukasaHarushige en-aut-sei=Nakatsukasa en-aut-mei=Harushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimuraYukio en-aut-sei=Nishimura en-aut-mei=Yukio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsujiTakao en-aut-sei=Tsuji en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama Univeristy affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University affil-num=7 en-affil= kn-affil=Okayama University affil-num=8 en-affil= kn-affil=Okayama University affil-num=9 en-affil= kn-affil=Kyushu University affil-num=10 en-affil= kn-affil=Okayama University en-keyword=cathepsin B kn-keyword=cathepsin B en-keyword=colorectal cancer kn-keyword=colorectal cancer en-keyword=colorectal adenoma kn-keyword=colorectal adenoma END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=6 article-no= start-page=293 end-page=297 dt-received= dt-revised= dt-accepted= dt-pub-year=1996 dt-pub=199612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Increased endothelial and epidermal thrombomodulin expression and plasma thrombomodulin level in progressive systemic sclerosis. en-subtitle= kn-subtitle= en-abstract= kn-abstract=To clarify the relation between systemic and cutaneous vascular endothelial injury in progressive systemic sclerosis (PSS), we examined thrombomodulin (TM) expression in PSS skin lesions immuno-histopathologically and compared it with plasma soluble TM levels measured by specific enzyme-linked immunosorbent assay. The plasma soluble TM level in PSS patients was significantly higher than that of normal controls and was as high as the levels of SLE patients. In relation to disease activities, the plasma TM levels of sclerotic phase PSS patients were significantly higher than that of atrophic phase PSS patients. The plasma samples with anti-Scl-70 antibody showed a high TM level than samples with anti-centromere antibody or anti-RNP antibody. Barnett's types or systemic corticosteroid treatment did not affect the TM level. Histopathologically, the dermal endothelial TM expression significantly increased in the sclerotic skin and moderately increased in the non-sclerotic skin of PSS compared with that of normal control skin. In addition, immunoreactive TM expression in the epidermis also increased in PSS. Disease activity-dependent elevation of plasma TM levels and immuno-histopathological expression of TM suggested generalized endothelial and epidermal cell involvement in PSS, and compensation in part by overproduction of TM by endothelial cells.
en-copyright= kn-copyright= en-aut-name=MizutaniHitoshi en-aut-sei=Mizutani en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiTatsuya en-aut-sei=Hayashi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NouchiNobuhiro en-aut-sei=Nouchi en-aut-mei=Nobuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InachiShin en-aut-sei=Inachi en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SuzukiKoji en-aut-sei=Suzuki en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimizuMasayuki en-aut-sei=Shimizu en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Mie University Faculty of Medicine affil-num=2 en-affil= kn-affil=Mie University Faculty of Medicine affil-num=3 en-affil= kn-affil=Mie University Faculty of Medicine affil-num=4 en-affil= kn-affil=Mie University Faculty of Medicine affil-num=5 en-affil= kn-affil=Mie University Faculty of Medicine affil-num=6 en-affil= kn-affil=Mie University Faculty of Medicine en-keyword=thrombomodulin kn-keyword=thrombomodulin en-keyword=scleroderma kn-keyword=scleroderma en-keyword=skin kn-keyword=skin en-keyword=endothelial cells kn-keyword=endothelial cells en-keyword=keratinocyte kn-keyword=keratinocyte END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=6 article-no= start-page=325 end-page=333 dt-received= dt-revised= dt-accepted= dt-pub-year=1996 dt-pub=199612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Relation between the instrumental activities of daily living and physical fitness tests in elderly women. en-subtitle= kn-subtitle= en-abstract= kn-abstract=A cross-sectional study was conducted to quantitatively evaluate the relationship between the instrumental activities of daily living (IADL) and various physical fitness tests in elderly women living at home. The study focused on the total population of those women aged 65 years and over living in Y Town, Hyogo Prefecture, Japan, who visited a nursing home for day services. A total of 128 subjects were divided into two groups: dependent in IADL group (n = 49) and independent in IADL group (n = 79). The magnitude of the relation was evaluated by the odds ratio (OR). The following tests showed a significant decrease in IADL: knee-raising test [age-adjusted OR = 4.23, 95% confidence interval (CI) 1.81-9.87], height (age-adjusted OR = 4.09, 95% CI 1.75-9.56), grip strength (age-adjusted OR = 3.68, 95% CI 1.57-8.60), sit-and-reach test (age-adjusted OR = 2.76, 95% CI 1.20-6.34), and standing on one leg with closed eyes (age-adjusted OR = 2.56, 95% CI 1.09-5.97). Multivariate analysis using Hayashi's quantification method I indicated that knee-raising was the test most highly correlated with decreased IADL. These results suggest that measurement of knee-raising ability, muscle strength of the lower extremities and flexibility of hip joint could be the most useful factors to assess the level of instrumental self-support ability.
en-copyright= kn-copyright= en-aut-name=UchidaHayato en-aut-sei=Uchida en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MinoYoshio en-aut-sei=Mino en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsudaToshihide en-aut-sei=Tsuda en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BabazonoAkira en-aut-sei=Babazono en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawadaYuichi en-aut-sei=Kawada en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ArakiHidetoshi en-aut-sei=Araki en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OgawaTakanori en-aut-sei=Ogawa en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AoyamaHideyasu en-aut-sei=Aoyama en-aut-mei=Hideyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Okayama University Medical School affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama Univeristy affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University affil-num=7 en-affil= kn-affil=Okayama University affil-num=8 en-affil= kn-affil=Kyusyu University en-keyword=elderly women living at home kn-keyword=elderly women living at home en-keyword=instrumental activities of daily living kn-keyword=instrumental activities of daily living en-keyword=physical fitness test kn-keyword=physical fitness test en-keyword=kneeraising ability kn-keyword=kneeraising ability END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=6 article-no= start-page=319 end-page=324 dt-received= dt-revised= dt-accepted= dt-pub-year=1996 dt-pub=199612 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Immortalization of Cells from Brains Derived from a Strain (MSM/MSfB6C3F1) of Wild Mouse en-subtitle= kn-subtitle= en-abstract= kn-abstract=Escape from cellular aging is the rate-limiting step of multistep carcinogenesis. While normal human cells invariably undergo cellular aging and almost never spontaneously immortalize, cells derived from rodents such as mice are relatively easily immortalized. In this experiment, we studied the immortalization patterns of cells obtained from brain tissues of an inbred strain (MSM/MSfB6C3F1) derived from wild mice. We established 12 cell strains derived from 12 mouse brains in order to investigate whether these cells show cellular aging in the same fashion as human cells or whether these cells are immortalized as easily as rodent cells reported previously. As a result, all cell strains were immortalized up to about 200 days in culture. One strain immortalized very early, in the first 50 days, four strains immortalized in the last 200 days, and the other seven strains became immortal between 150 and 200 days in culture. All immortalized cell strains showed varying amounts of chromosome abnormalities, numerically and structurally, but no specific changes related to immortalization were detected. Before immortalization, three types of cells, glial-like, polygonal flat-thin, and fibroblast-like cells, were observed in culture, but after immortalization most of the cultures became fibroblastic. From these results, we concluded that fibroblast-like cells derived from brains of these mice immortalized in like fashion to fibroblasts of other inbred mice.
en-copyright= kn-copyright= en-aut-name=YuasaTakae en-aut-sei=Yuasa en-aut-mei=Takae kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AbeEriko en-aut-sei=Abe en-aut-mei=Eriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OshimuraMitsuo en-aut-sei=Oshimura en-aut-mei=Mitsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NambaMasayoshi en-aut-sei=Namba en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Tottori University affil-num=4 en-affil= kn-affil=Okayama University en-keyword=cells from mouse brains kn-keyword=cells from mouse brains en-keyword=immortalization kn-keyword=immortalization en-keyword=aging kn-keyword=aging en-keyword=chromosomes kn-keyword=chromosomes END