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Biomedical subjects

T Ito

Publications and source records attributed to T Ito.

At least 91 records · Page 5Linked to original sources

Nucleosome assembly and remodeling.

Packaging of the eukaryotic genome into chromatin functions not only to constrain the genome within the boundaries of the cell nucleus but also to permit dynamic and broad-ranging changes related to many important biological phenomena. Therefore, chromatin assembly is a process that affects DNA replication, repair, and gene expression. Chromatin structure is linked to transcriptional regulation, and recent studies show how chromatin is altered so as to facilitate transcription. In addition, modification of chromatin structure is an important regulatory mechanism. Here I review the mechanism of chromatin assembly in vitro and the changes of chromatin structure related to transcriptional activation.

Animals↗

Analysis of dystrophin mRNA from skeletal muscle but not from lymphocytes led to identification of a novel nonsense mutation in a carrier of Duchenne muscular dystrophy.

Dystrophin mRNA expressed in peripheral lymphocytes of individuals with X-linked Duchenne muscular dystrophy (DMD) has been used as a source material for mutation analysis. Here we present the first report of failure of isolation of nonsense dystrophin mRNA in lymphocytes but success in skeletal muscle in a female carrier of DMD. The mutation responsible for dystrophin-negative muscle fibers of the carrier was analysed by direct sequencing of the reverse transcription PCR product of dystrophin mRNA. In her peripheral lymphocytes, no nucleotide change was detected in the 14 kb long mRNA. Remarkably, a novel nucleotide change of C1682T in exon 12, changing glutamine codon to stop codon (Q492X) was found to be present in her skeletal muscle. This change was heterozygous. Analysis of her genomic DNA disclosed heterozygous C and T nucleotides at nt 1682, confirming the genomic origin of the nonsense mutation. Although dystrophin cDNA prepared from lymphocytes was sequenced again after subcloning, mutation-retaining clone could not be isolated. This lymphocyte-specific disappearance of nonsense mRNA strongly suggested tissue-specific skewing of X-inactivation. However, both paternal and maternal dystrophin alleles were shown to be equally expressed in lymphocytes as well as in muscle, indicating no skewing of X-inactivation in lymphocytes. We concluded that the dystrophin mRNA of the DMD carrier was destabilized in lymphocytes. Our results indicated that analysis of mRNA in lymphocytes is not enough for exact carrier diagnosis of Duchenne muscular dystrophy.

Adult↗

Anthropogenic radionuclides in the Japan Sea: their distributions and transport processes.

The anthropogenic radionuclides, (90)Sr, (137)Cs and (239+240)Pu, were measured in the water column of the Japan Sea/East Sea during 1997-2000. The vertical profiles of radionuclide concentrations showed: exponential decrease with depth for (90)Sr and (137)Cs, and surface minimum/subsurface maximum for (239+240)Pu. These results do not differ substantially from results reported previously. The area-averaged concentrations of radionuclides in the Japan Sea are higher than those found in the Northwest Pacific Ocean below surface layer showing the accumulation of the radionuclides in the deep waters in the Japan Sea. Concerning spatial distributions, the area of high (137)Cs inventory extends from the Japan Basin into the Yamato Basin. It is suggested that wintertime convection of water, occurring mainly in the Japan Basin, causes the radionuclides to sink. The nuclides then advect into the Yamato Basin after detouring around the Yamato Rise.

Environmental Monitoring↗

Growth inhibition through activation of peroxisome proliferator-activated receptor gamma in human oesophageal squamous cell carcinoma.

Peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimerises with retinoid X receptor alpha (RXRalpha) and is thought to be a novel therapeutic target for human malignancies. We evaluated the ability of troglitazone (TRO) alone or in combination with 9-cis retinoic acid (9CRA), ligands of PPARgamma and RXRalpha, respectively, to inhibit the growth of oesophageal squamous cell carcinoma (OSCC). All 10 tested OSCC cell lines of a KYSE series expressed PPARgamma and RXRalpha at both the mRNA and protein levels. In four tested cell lines, TRO inhibited growth, and a synergistic effect was observed with simultaneous 9CRA application. In KYSE 270 cells, a luciferase reporter assay showed that the simultaneous application of TRO and 9CRA to the cells increased the relative luciferase activity approximately 20-fold compared with the controls without TRO or 9CRA application. In this cell line, flow cytometry demonstrated that combined treatment with TRO and 9CRA greatly increased the sub-G1 phase, and Hoechst 33342/propidium iodide (PI) staining showed that apoptotic cell death was mainly induced through ligand treatment. In addition, implanted tumours in nude mice showed significant inhibition of tumour growth when treated with TRO. These results suggest that the PPARgamma/RXRalpha heterodimer may be a new therapeutic target for OSCC.

Alitretinoin↗

Allopurinol challenge tests performed before and after living-related donor liver transplantation in citrullinaemia.

We performed allopurinol challenge tests to evaluate the metabolic state of a citrullinaemic patient who received a living-relative donor liver transplant. Before transplantation, large amounts of orotic acid and orotidine were excreted during the challenge test. Following transplantation, excretion of these compounds in response to allopurinol was normalised. The challenge test was a safe and useful method to evaluate the metabolic state of the patient.

Allopurinol↗

Pneumocephalus following an epidural blood patch.

Pneumocephalus is a rare complication of epidural block. We report a case of pneumocephalus complicating an epidural blood patch performed 3 days after unintentional dural puncture. Pneumocephalus may occur during an epidural blood patch procedure, even if the epidural needle tip is within the epidural space.

Aged↗

Analyses of dendritic cell subsets in pregnancy.

PROBLEM: Changes in the frequency of dendritic cell (DC) subsets in the peripheral blood were analyzed as pregnancy progressed, and the effects of human chorionic gonadotropin (hCG) on myeloid and lymphoid DC subsets were phenotypically and functionally examined. METHOD OF STUDY: Two major subsets of DCs were prepared from the peripheral blood by flow cytometry. Major histocompatibility complex class II molecules and adhesion/costimulatory molecules were examined before and after culture with hCG. hCG receptors on both DC subsets were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The frequency of myeloid DCs increased in the late stage of pregnancy, while that of lymphoid DCs gradually decreased. The addition of hCG (physiological concentrations in pregnancy) to cultures induced the maturation of both DC subsets in conjunction with increases in the expression of adhesion/costimulatory molecules, their stimulatory activities in allogeneic mixed lymphocyte/leukocyte reaction, and cytokine secretion (interleukin-12 and interferon-gamma). hCG receptors were found in both DC subsets by RT-PCR, suggesting that these stimulatory activities of hCG are mediated by hCG receptors on the DCs. CONCLUSIONS: hCG can modulate immune responses through the activation of myeloid and lymphoid DCs.

Bone Marrow↗

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

Adenoviridae↗

Regeneration of hypogastric nerve using a polyglycolic acid (PGA)-collagen nerve conduit filled with collagen sponge proved electrophysiologically in a canine model.

The hypogastric nerve (HGN) is a sympathetic nerve in the peritoneal cavity and controls urinary and seminal functions. In this study, the regeneration of HGN was determined by using a new type of an artificial nerve conduit, polyglycolic acid (PGA)-collagen nerve conduit filled with collagen sponge in two dogs. A PGA-collagen nerve conduit (diameter=2 mm) was interposed in a 10 mm gap of the right HGN. The regeneration of the HGN was evaluated electrophysiologically 8 months after the operation. The intraluminal pressure of spermatic duct and the bladder neck were elevated 80 mmHg and 25 mmHg respectively by the stimulation across the regenerated HGN. The prostate contraction was also elicited. The responses diminished after the excision of the regenerated portion of HGN. These results proved the regeneration of HGN and this nerve conduit will be great help for patients who suffer from urinary and seminal disturbances.

Animals↗

Chromosomal instability and human hepatocarcinogenesis.

Recently, many studies have identified losses and gains of several chromosomal loci in human hepatocellular carcinoma (HCC) with fine microsatellite analysis and comparative genomic hybridization. Although distribution of aberrant chromosomal arms differs among HCCs, loss of 1p, 4q, 6q, 8p, 9p, 10q, 13q, 16q and 17p, and gain of 1q, 6p, 8q, 17q and 20q have been recurrently reported, and loss of 4q and 16q seems to occur preferentially in hepatitis B virus-related HCCs. Accumulation of these aberrant chromosomal regions is associated with tumor progression, and some chromosomal aberrations, such as loss of 1p, are frequently identified in well-differentiated HCCs and also detected even in dysplastic nodule and cirrhotic nodule. This evidence suggests that chromosomal instability (CIN) emerges at an early stage during hepatocarcinogenesis and is successively inherent to tumor cells, resulting in acquisition of malignant phenotype. The molecular basis of CIN is beginning to be explored; however, several mechanisms may be involved for CIN of HCC.

Allelic Imbalance↗

Effect of nitrite and nitrate on biogenic sulfide production in sewer biofilms determined by the use of microelectrodes.

The effects of O2 and NO3- concentrations on in situ sulfate reduction and sulfide reoxidation in microaerophilic wastewater biofilms grown on rotating disk reactors were investigated by the use of microelectrodes for O2, S2-, NO3-, NO2-, and pH. Microelectrode measurements showed the vertical microzonation of O2 respiration, NO3- respiration, H2S oxidation and SO4(2-) reduction in the biofilms. The microelectrode measurements indicate that sulfate reducing activity was largely restricted to a narrow anaerobic zone located about 500 microm below the biofilm surface. An addition of nitrate forced the sulfate reduction zone deeper in the biofilm and reduced the specific sulfate reduction rate as well. The sulfate reduction zone was consequently separated from the O2 and NO3- respiration zones. Anaerobic H2S oxidation with NO3- was also induced by addition of nitrate to the medium. Measurements of the reduced inorganic sulfur compounds (FeS, FeS2 and S0), total-Mn and total-Fe in the biofilm indicated that the produced H2S became immediately oxidized with O2, NO3- and other oxidants, mainly ferric/ferrous hydrates. On the basis of the present results, it was estimated that of all sulfide produced, 13% of the sulfide was precipitated by metal ions as FeS and S0 just above the sulfate reduction zone, 65% was anaerobically oxidized to SO4(2-) with NO3- as an electron acceptor and 22% was aerobically oxidized within the biofilm incubated in 70 micromol l(-1) of DO and 280 micromol l(-1) of NO3-.

Biofilms↗

[Minimally invasive video-assisted thoracic surgery using radially expanding trocars].

We report a new and safer access device for thoracoscopic operation. This radially expanding trocar provides a smaller incision of skin and a lesser visceral, vascular or neural injury than a conventional cannula. Therefore, most of patients undergoing this operation do not feel much pain. Moreover, this device system is more cost effective than a conventional one. We prefer and recommend this minimally invasive technique for video-assisted thoracic surgery.

Equipment Design↗

Transfer function analysis of positron-emitting tracer imaging system (PETIS) data.

Quantitative analysis of the two-dimensional image data obtained with the positron-emitting tracer imaging system (PETIS) for plant physiology has been carried out using a transfer function analysis method. While a cut leaf base of Chinese chive (Allium tuberosum Rottler) or a cut stem of soybean (Glycine max L.) was immersed in an aqueous solution containing the [18F] F- ion or [13N]NO3- ion, tracer images of the leaf of Chinese chive and the trifoliate of soybean were recorded with PETIS. From the time sequence of images, the tracer transfer function was estimated from which the speed of tracer transport and the fraction moved between specified image positions were deduced.

Allium↗

Extraction of knowledge on protein-protein interaction by association rule discovery.

MOTIVATION: Protein-protein interactions are systematically examined using the yeast two-hybrid method. Consequently, a lot of protein-protein interaction data are currently being accumulated. Nevertheless, general information or knowledge on protein-protein interactions is poorly extracted from these data. Thus we have been trying to extract the knowledge from the protein-protein interaction data using data mining. RESULTS: A data mining method is proposed to discover association rules related to protein-protein interactions. To evaluate the detected rules by the method, a new scoring measure of the rules is introduced. The method allowed us to detect popular interaction rules such as "An SH3 domain binds to a proline-rich region." These results indicate that the method may detect novel knowledge on protein-protein interactions.

Algorithms↗

Quantitative analysis of the energetics of DNA damage.

Application of Monte Carlo track structure has been very successful in the modelling and quantification of DNA damage, clustered-damage and spectrum of DNA damage for energetic electrons and ions. However, there are paradoxical axioms in quantitative assessment of the energetics of DNA damage at very low electron energy and in the vacuum UV region. This paper, after a brief review of the parameters used in modelling of DNA damage, presents an analysis of experimental data of strand breaks in aqueous solution in the vacuum UV, the region to which little attention has been paid in spite of its fundamental importance in providing reaction parameters for radiation actions.

Biophysics↗

Evaluation of aviguard, a commercial competitive exclusion product for efficacy and after-effect on the antibody response of chicks to Salmonella.

The competitive exclusion (CE) action of Aviguard (AG) and its effects on the antibody response of chicks were evaluated in this study. We observed that AG protected the chicks from overwhelming colonization. Fourteen days after infection, fewer AG-pretreated than nonpretreated chicks shed salmonellae from their coloaca in both infected groups, although much less from SE-infected chicks. Antibody titers of sera produced to Salmonella typhimurium (ST) and SE in pretreated and non-pretreated chicks were not significantly different. Immunoblotting showed that these antibodies reacted with SDS-PAGE-separated 71.4, 67.7, 44.0, and 30.3 kDa proteins detectable in the test strains. Few weak bands of doubtful significance were observed in the cross-reaction between the sera of ST- and SE-infected chicks with ST and SE antigens, respectively. Our study showed that AG protected chicks from overwhelming colonization by salmonellae, and neither altered the antigenic proteins of infecting salmonellae nor their recognition by specific antibodies produced in response to the infection.

Animals↗

Beneficial effect of JTV-803, a new synthetic inhibitor of activated factor X, against both lipopolysaccharide-induced and tissue factor-induced disseminated intravascular coagulation in rat models.

We examined whether JTV-803, a specific activated factor X inhibitor independent of antithrombin III (ATIII), is effective against disseminated intravascular coagulation (DIC) in rat models induced by tissue factor (TF) or lipopolysaccharides (LPS). In male Wistar rats, DIC was induced by a 4 h infusion of thromboplastin (3.75 U/kg) or LPS (50 mg/kg). The rats were given JTV-803 (0.3 or 3 mg/kg, bolus intravenously) (JTV-803 groups) or low molecular weight heparin (LMWH groups) (200 U/kg, bolus intravenously) prior to an injection of TF or LPS. The results showed that JTV-803 was dose-dependently effective against DIC in both TF-induced and LPS-induced rat models. This anti-DIC effect of JTV-803 at higher doses was almost equivalent to that of LMWH in both types of DIC. Plasma ATIII activity was more prominent in the group treated with JTV-803 than in that treated with LMWH. None of rats died in the TF-induced DIC model with or without drug administration. On the contrary, seven of 22 rats died (mortality rate, 31.8%) in the LPS-induced DIC model without drug administration. Although the mortality rate of rats induced with LPS and treated with LMWH was quite high (6/16, 37.5%), none of the LPS-induced rats treated with JTV-803 died. These findings suggested that JTV-803 can treat both TF-induced and LPS-induced DIC models, and that this drug has greater potential in preserving ATIII and in improving the prognosis of DIC.

Animals↗