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Multiple transferrin-independent iron uptake (Tf-IU) systems are known to be involved in the internalization of free iron salt in various mammalian cells. However, the characteristics of a Tf-IU system in cortical cells are not clear. In this study, we characterized the Tf-IU systems in both cortical and glial predominant (GP) cells from rat cerebral cortex to investigate the mechanism by which iron (Fe) or aliminum (Al) accumulates in the cerebral cortex. The Tf-IU systems in both cells were temperature- and Ca2+-dependent. The upregulation of Tf-IU system in GP cells by Fe- or Al-nitrilotriacetate (Fe- or Al-NTA) was 2- or 4-fold higher than that of cortical cells. Chemiluminescence analysis specific for O2‾ and 1O2 also showed that the production of active oxygen species in Fe-loading GP cells was twice higher than that of Fe-loading cortical cells. These results suggest the existence of Tf-IU systems in both cortical and GP cells similar to those of HeLa cells whose Tf-IU is metal- and Ca-2+ dependent, and that the glial cells contribute to metal accumulation in cerebral cortex. The present study may help to explain the pathogenesis of neurodegenerative disorders caused by inducing oxidative stress.departmental bulletin pape
To elucidate the mechanism for cell growth arrest in relation to apoptosis mediated by the p53 gene, I studied two p53-null human cancer cell lines (K562 and Jurkat) carrying a human p53 temperature sensitive (ts) mutant (p53138val). The cell growth in the newly established K562 cells carrying the ts mutant was arrested in G0/G1 at the permissive temperature (32.5℃), at least in part, due to induction of p21/waf1. In apoptosis-induced Jurkat cells upon temperature shift-down, a lower level of p21 induction relative to that of MDM2 was observed in comparison with that in K562 cells. Meanwhile, levels of bax and bcl-2 expression were relatively constant upon temperature shift-down in both cell lines. Studies on the phosphorylation pattern of Rb family proteins, and results of gelshift and antibody super-shift assays showed the accumulation of Rb/E2F complexes in growth-arrested K562 cells, but no such phenomenon was observed in Jurkat cells. Taken together, the results are consistent with the idea that a higher level of p21 expression and its subsequent Rb/E2F complex formation played an important role in the growth arrest of K562 cells.departmental bulletin pape
Articles concerning mathematical formulation of proliferating cells in well-mixed batch culture are reviewed. An age-structured formulation which takes varying generation times into consideration is shown to be able to explain the partial synchronization observed when the cells in the batch culture are starved. With this formulation, significance of the logarithmic phase is reconsidered. Further, the formulation is applied to describe age-structured population dynamics in fed-drained culture.departmental bulletin pape
Due to the general aging of society, increasing national medical expenditures are becoming a serious problem. It is thus highly desirable to reduce the need for medical services by maintaining the population in good health. Intensive monitoring of health parameters will become a necessary means for attaining good health at all times. Technology for health monitoring, however, is only recently being developed. A concept of home health monitoring is proposed by which health parameters are automatically monitored at home without disturbing daily activities. There are many attempts being made to realize this concept. This article reviews these attempts at developing home health monitoring techniques, which include monitoring during sleep, via the bath tub or toilet seat, as well as during daily activites. Preliminary studies show that home health monitoring can be achieved even by means of simple sensors and instruments. There are also many possible applications for advanced technologies. Potential future technologies for home health monitoring include automatic blood pressure measurement via the toilet seat, automatic blood sampling with a device mimicking a mosquito, and artificial noses for detecting smells.departmental bulletin pape
Propofol is a widely used intravenous anesthetic, which is known to affect cardiac functions. Cardiac effects may be caused by direct actions on ion channels of the heart. While effects of propofol on several ion channels have been studied at the whole cell and single-channel levels, its effects, if any, on anion currents have yet to be examined. Effects of propofol on Ca2+-activated Cl-current (Icl(ca)) were investigated in single myocytes isolated from rabbit ventricles by the whole-cell patch clamp technique at 36℃.Icl(ca) was activated by perfusing internal solutions with 0.1 µM free Ca2+ in the absence and presence of 10 mM internal Na+, eliciting Ica-dependent and -independent component, respectively. By the application of propofol (0.1-300 µM), Ica-independent Icl(ca) was strongly inhibited in a dose-dependent manner with an IC50 of about 5 µM. The blocking effects of propofol were voltage independent. On the other hand, the Ica-dependent component of Icl(ca) was little affected by propofol at concentrations of up to 50 µM. The outward Na+/Ca2+ exchanger current was also blocked by application of 5 µM propofol. We conclude that propofol inhibits cardiac Icl(ca) in rabbit ventricular myocytes, mainly the Ica-independent component, at therapeutic concentrations. The inhibition may be due to block of a reverse mode of Na+/Ca2+ exchange current.departmental bulletin pape
To evaluate the vibrational characteristics of the maxillary arch, modal analysis was applied to human subjects. Twelve healthy human subjects and 2 cleft lip and palate (CLP) subjects with surgical failure in their cleft area were chosen for this study. The main measurement system was composed of an impact hammer, acceleration sensor, CF-6400 FFT Analyzer, PC-9821Xn personal computer, and Vibrant PC modal analysis software. The measurement points were established on 12 teeth between the upper first molars on both sides of the mouth in healthy subjects, and on 10 teeth in CLP subjects. In all subjects, one distinct resonance peak was observed in each transfer function at each measurement point. All of the transfer functions of a given subject strongly resembled each other in terms of shape. The amplitude and modal shapes of the maxillary arches of all the subjects were obtained by using a curve-fitting function in the software. In the healthy subjects, the maxillary arch expanded outward and shrank inward on vibration with no node after an impact. In the CLP subjects, the phase lag between the large and small segment was distinctly observed after an impact. In this study, the applicability of modal analysis for human subjects was demonstrated.departmental bulletin pape
The occurrence of apoptosis and cell proliferation in hereditary intestinal diseases was analyzed for possible diagnostic markers that could discriminate the formation of tumors that would develope into cancer. In all, 15 adenomas in familial adenomatous polyposis, 3 juvenile polyposis, 5 Peutz-Jeghers syndrome, 14 sporadic adenomas, and 46 colorectal carcinomas were investigated. Tissue specimens were examined for apoptotic cells by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and proliferating cells by immunohistochemistry of proliferating cells nuclear antigen (PCNA).In hereditary intestinal diseases, the apoptotic and proliferating indexes were significantly lower than those in colorectal carcinoma, and higher apoptotic and proliferating indexes were observed in poorly differentiated colorectal adenocarcinoma and in subserosal stages of invasion. There were no significant differences in proliferating and apoptotic indexes between adenoma in FAP and sporadic adenoma. No apoptotic and proliferating cells were observed in juvenile polyposis, and only occasional proliferating cells were seen in Peutz-Jeghers syndrome. These findings demonstrated that TUNEL and PCNA staining are useful in correctly reflecting disease progression in hereditary intestinal diseases.departmental bulletin pape
We have previously identified a novel gene, Nau (Neuron-specific gene, which has a number of AU-rich RNA instability motifs), from a quail spinal cord cDNA library. Nau expression was observed mainly in post-mitotic neuroblasts, especially in the stage of axonogenesis. In this study, we cloned its chick orthologue (cNau, 5069 bp), which encodes 369 amino acid residues. cNau's open reading frame has three highly conserved regions with rat STOP (stable tubule-only polypeptide). cNau may be an orthologue of STOP gene considering its uniqueness in zoo blot analysis and its sequence similarity. Both the genetic structure and temporo-spatial expression patterns indicate that the cNau gene may be related to axonogenesis. In the hindbrain, cNau mRNA was accumulated in rhombomere boundary regions and in the rhombomere 2, 4 and 6. These observations suggest a specific role of cNau in the hindbrain or the difference indevelopment between the hindbrain and spinal cord.departmental bulletin pape
The purpose of this study was to evaluate a hydroxyapatite (HA)-collagen (Col)-bone morphogenetic protein (BMP) composite as an osteoinductive bone substitute. Partially-purified BMP from bovine bone was mechanically mixed with highly purified type I collagen from calf dermis and then subsequently mixed with pure synthetic hydroxyapatite granules or block. The HA-Col-BMP composite, or the HA-Col composite as a control, was implanted in a surgically-induced mandible bone defect (6×7×10 mm) in an adult Japanese monkey. The mandible was excised three months after implantation and studied histologically. The BMP-containing implant induced much more new bone than the control implant in all experimental animals of each group, with either HA granules or HA block. Newly formed bone was attached tightly to HA and infiltrated deeply into the pores of the HA of the BMP-containing implant, while fibrous tissue existed between the host bone and HA in the control implant. Thus, we conclude that an HA-Col-BMP composite could be a superior biomaterial for a bone substitute.departmental bulletin pape