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41.
Accelerated Loss of Islet β Cells in Sucrose-Fed Goto-Kakizaki Rats, a Genetic Model of Non-Insulin-Dependent Diabetes Mellitus
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Motoi Koyama Ryu-ichi Wada Hiroyasu Sakuraba Hiroki Mizukami Soroku Yagihashi 《The American journal of pathology》1998,153(2):537-545
The Goto-Kakizaki (GK) rat is a spontaneously diabetic animal model of non-insulin-dependent diabetes mellitus, which is characterized by progressive loss of β cells in the pancreatic islets with fibrosis. In the present study, we examined the effects of sucrose feeding on the islet pathology in this model. Six-week-old GK rats were fed with 30% sucrose for 6 weeks to induce severe hyperglycemia, and their condition was compared with that of nontreated rats. Age-matched normal Wistar rats were also given sucrose for the same periods and used for comparison. The sucrose-treated GK rats showed elevated blood glucose levels on oral glucose tolerance tests at 60 minutes and 120 minutes, representing 123% and 127% of values in untreated GK rats, respectively. At the end of the study, the mean β-cell volume density in GK rats was 50% less than that in untreated Wistar rats. Sucrose feeding further reduced the volume densities of β cells to only 50% of the levels of age-matched GK rats. Apoptotic cells were found in islet β cells only in GK rats fed sucrose (mean 0.067%). There appeared to be more islets that immunohistochemically stained strongly positive with 8-hydroxy-deoxyguanosine as a marker of oxidative damage of DNA in GK rats fed sucrose compared with those not given sucrose. GK rats not fed sucrose showed significantly lower proliferative activity of β cells measured by 5-bromo-2′-deoxyuridine uptake and intensified expression of Bcl-2 immunoreactivities at 6 weeks of age compared with those in age-matched Wistar rats. These two indices were reduced in both GK and Wistar rats with increasing age and were not affected by sucrose feeding in either group. The present study thus indicated that sucrose feeding promoted the apoptosis of β cells in GK rats through increased oxidative stress without altering their proliferative activity. 相似文献
42.
Nakata H Inui K Wasaka T Tamura Y Kida T Kakigi R 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2005,162(3):293-299
The present study investigated the characteristics of the middle-latency negative potential of event-related potentials (ERPs) using somatosensory go/nogo tasks. We manipulated interstimulus interval (ISI) in Experiment 1 and stimulus probability in Experiment 2 and analyzed the subtracted difference waveform resulting from subtraction of the ERP evoked by the go stimulation from that evoked by the nogo stimulation. In Experiment 1, the peak latency of negativity became significantly longer as the ISI increased, but the peak amplitude was unchanged. The reaction time (RT) was longer with increasing ISI. In Experiment 2, manipulation of the stimulus probability yielded an increase in peak amplitude with decreasing probability of the nogo stimulus, but did not affect the latency. The RT increased as the probability of a nogo stimulus rose. Because manipulation of the ISI and stimulus probability elicited different brain activities, we hypothesized that manipulation of the ISI elicited a delay of the stimulus evaluation process including response inhibition, and that stimulus probability significantly affected the strength of the response inhibition process. 相似文献
43.
Hiroki Kurahashi Kenzo Akagi Ikuo Yana Thomas Melot Olivier Delattre Gilles Thomas Shintaro Okada Shin-ichiro Takai Isamu Nishisho 《Journal of human genetics》1994,39(2):243-248
Summary Eight cosmid clones were regionally assigned to small subregions of chromosome 22 by hybridization with a total of 22 somatic cell hybrids. One cosmid was localized to the proximal part of 22q which contained the region commonly deleted in the DiGeorge syndrome. Seven cosmids showing restriction fragment length polymorphisms were localized to the telomeric region distal to the MB locus, which was reported to be frequently deleted in sporadic meningioma. These cosmids, when finely mapped and ordered, are considered useful for the identification of genetic alterations on this chromosome arm. 相似文献
44.
Expression of cytoplasmic TFF2 is a marker of tumor metastasis and negative prognostic factor in gastric cancer 总被引:8,自引:0,他引:8
Dhar DK Wang TC Maruyama R Udagawa J Kubota H Fuji T Tachibana M Ono T Otani H Nagasue N 《Laboratory investigation; a journal of technical methods and pathology》2003,83(9):1343-1352
Trefoil factor family 2 (TFF2) is a small peptide constitutively expressed in the gastric mucosa, where it plays a protective role in restitution of gastric mucosa. TFF2 has also been shown to be expressed in some gastric cancers, but its role in tumor metastasis and patient prognosis has not been examined. In this study, we examined TFF2 expression at both the mRNA and protein levels and correlated these results with the clinicopathologic characteristics and prognosis of gastric cancer patients. Among the 144 curatively resected samples, 43 (30%) were positive for TFF2. TFF2 expression was preferentially observed in the infiltrating tumor cells sparing the superficial cells. Significantly increased expression of TFF2 was noted in large tumors of the diffuse type. An increased prevalence of TFF2 expression was also found in tumors with advanced T and N stage and in patients with lymphatic and venous invasion. Accordingly, patients with TFF2-expressing tumors had a significantly worse disease-free survival, and in multivariate analysis, this finding remained significant as an independent prognostic factor. Taken together, our results suggest that TFF2 expression may play a role in gastric cancer invasion and as such could be a useful target for therapeutic intervention. 相似文献
45.
Biological properties and gene expression associated with metastatic potential of human osteosarcoma 总被引:4,自引:0,他引:4
Nakano T Tani M Ishibashi Y Kimura K Park YB Imaizumi N Tsuda H Aoyagi K Sasaki H Ohwada S Yokota J 《Clinical & experimental metastasis》2003,20(7):665-674
Lung metastasis has a great influence on the prognosis of patients with osteosarcoma. We previously established two high-metastatic
sublines, M112 and M132, from the HuO9 human osteosarcoma cell line by in vivo selection. In this study, we newly isolated a high-metastatic subline, H3, and three low-metastatic sublines, L6, L12 and
L13, from HuO9 by the dilution plating method. Three high-metastatic sublines produced more than 200 metastatic nodules in
the lung, while three low-metastatic sublines produced no or few nodules after injection of 2 × 106 cells into the tail vein of nude mice. There were significant differences in the motility and invasiveness between high-
and low-metastatic sublines, whereas the growth rates in vitro and the tumorigenicity in vivo showed no correlation with their metastatic abilities. Early adherence to culture plates was significantly lower in two of
three low-metastatic sublines, which occupied smaller surface areas on the culture plates than other sublines did. Comparison
of the expression of 637 cancer-related genes by cDNA microarray revealed that seven genes were differentially expressed between
high- and low-metastatic sublines. Among them, five genes (AXL, TGFA, COLL7A1, WNT5A, and MKK6) were associated with adherence, motility, and/or invasiveness. These results suggest that the differences in motility/invasiveness
and adhesive abilities are key determinants of lung metastasis in osteosarcoma.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
46.
WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production 总被引:6,自引:0,他引:6
Hamano S Himeno K Miyazaki Y Ishii K Yamanaka A Takeda A Zhang M Hisaeda H Mak TW Yoshimura A Yoshida H 《Immunity》2003,19(5):657-667
WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production. 相似文献
47.
Unlike acetylcholine, caffeine was much more effective in releasing catecholamine in the absence of extracellular Ca2+ than in its presence in perfused cat adrenal glands. The intracellular Ca2+ antagonist, TMB-8 (10−4 M), inhibited reversibly the catecholamine secretion evoked by caffeine (40 mM) and that induced by acetylcholine (10−4 M) in the presence of hexamethonium (10−3 M) during perfusion with Ca2+-free Locke solution containing EGTA (10−5 M). These results support our view that muscarinic receptor activation causes catecholamine secretion by mobilizing Ca2+ from an intracellular pool just as caffeine does. 相似文献
48.
Lura Brianna Caddle Jeremy L. Grant Jin Szatkiewicz Johann van Hase Bobbi-Jo Shirley Joerg Bewersdorf Christoph Cremer Alain Arneodo Andre Khalil Kevin D. Mills 《Chromosome research》2007,15(8):1061-1073
Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners,
and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation,
especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms
of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes
occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into
‘neighborhoods’ comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning,
neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could
induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested
whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods
comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These
findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary
lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular
etiology of tumor-specific translocation patterns. 相似文献
49.
Yoshihisa Umekita Nobumasa Enokizono Yoshiatsu Sagara Kazumi Kuriwaki Takashi Takasaki Aichi Yoshida Hiroki Yoshida 《Virchows Archiv : an international journal of pathology》1992,420(4):345-351
Summary In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF- and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-; positive EGF-R and TGF-; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF- correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF- are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immuno-histochemical demonstration of expression of EGF-R and TGF- may provide useful information for selecting the appropriate treatment. 相似文献
50.
Shoichi Fujita Eisei Shin Tsutomu Nakamura Hiroki Kurahashi Yasufumi Kaneda Kiyoji Tanaka Takesada Mori Shin-ichiro Takai Isamu Nishisho 《Journal of human genetics》1993,38(4):361-370
Summary Radiation-reduced hybrids for mapping of DNA markers in the pericentromeric region of chromosome 10 were developed. A Chinese hamster/human somatic cell hybrid (762-8A) carrying chromosomes 10 and Y as the only human material were exposed to 40,000 rads of irradiation and then rescued by fusion with non-irradiated recipient Chinese hamster cells (GM459). Southern hybridization analyses revealed that 10 of 128 HAT-resistant clones contained human chromosomal fragments corresponding to at least one marker locus betweenFNRB (10p-11.2) andRBP3 (10q11.2). These hybrids were then used to map microdissection clones previously isolated and roughly mapped to this chromosomal region by fluorescencein situ hybridization (FISH). Two of the six microclones studied could be mapped to the proximity of the D10-S102 locus. These radiation hybrids are useful for the construction of refined genetic maps of the pericentromeric region of chromosome 10. 相似文献