PubMed Health⌕ Search

Biomedical subjects

Takashi Imai

Publications and source records attributed to Takashi Imai.

9 recordsLinked to original sources
PubMed2003

Beneficial effects of apolipoprotein A-I on endotoxemia.

PURPOSE: Although many studies have shown the beneficial effects of lipoproteins on animals with endotoxemia, little is known about the impact of apolipoprotein A-I (apoA-I) on tumor necrosis factor Alpha (TNF-Alpha) release in response to lipopolysaccharide (LPS). The present study was conducted to determine whether the administration of apoA-I inhibits the release of TNF-Alpha and influences the survival rate of rats with endotoxemia. METHODS: Forty male Wistar rats were divided randomly into four groups. Rats in the first and second groups were given 1 mg/kg LPS intraperitoneally (i.p.) and blood was collected 1 h later to measure the serum levels of TNF-Alpha. Either 10 mg/kg apoA-I or Tris-buffered saline was injected i.p. and the serum TNF-Alpha levels were measured again 2 h later. Rats in the third and fourth groups were given 5 mg/kg LPS. Following the administration of 10 mg/kg apoA-I or Tris-buffered saline, animals were observed for 5 days and survival rates were determined. RESULTS: ApoA-I inhibited the release of serum TNF-Alpha and improved the survival rates of rats with endotoxemia. CONCLUSION: The administration of apoA-I suppressed the TNF-Alpha release in endotoxemia and decreased the mortality rates of rats.

Animals↗
PubMed2003

Involvement of DNA-dependent protein kinase in down-regulation of cell cycle progression.

The catalytic polypeptide of DNA-dependent protein kinase (p470) is encoded by the gene responsible for murine severe combined immunodeficiency (SCID) devoid of DNA double-strand break repair and V(D)J recombination. Here, we have characterized the role of p470 in cell proliferation using SCID mice and the cell lines. In accord with DNA histogram patterns, SCID cell lines (SD/SD-eA and SC3VA2) expressing extremely low level of DNA-PK activity grew faster than a normal mouse cell line (CB/CB-eB) and SC3VA2 complemented with human p470 gene (RD13B2). In regenerating liver after partial hepatectomy, de novo DNA synthesis determined by [(3)H]thymidine incorporation started at 30h in C.B-17/Icr-SCID (SCID) mice and at around 36h in C.B-17/Icr (C.B-17) mice. Compared with normal cells, SCID cells contained slightly higher levels of transcripts of cyclin A, cyclin E, B-Myb and dihydrofolate reductase, which are regulated by E2F-1. E2F-1 playing a key role in G1- to S-phase progression was phosphorylated in vitro by DNA-PK. Importantly, the E2F-1 promoter transcriptional activity in SCID cell lines (SD/SD-eA and SC3VA2) was 4-5-fold higher than that in CB/CB-eB and RD13B2. These results suggest that p470 is involved in down-regulation of cell cycle progression through E2F-1-responsible genes.

Animals↗
PubMed2003

Influence of modest endotoxemia on postoperative antithrombin deficiency and circulating secretory immunoglobulin a levels.

OBJECTIVE: To evaluate the influence of modest endotoxemia on postoperative antithrombin deficiency and cholestasis. SUMMARY BACKGROUND DATA: It has not been determined whether endotoxin translocation in small amounts is a physiological phenomenon or whether it is a potential health hazard. METHODS: Blood endotoxin, antithrombin III (ATIII), secretory immunoglobulin A (sIgA), which was selected as a marker of cholestasis, C-reactive protein (CRP), and alpha-1-antitrypsin (AAT) concentrations were measured from the 20 patients undergoing curative gastrectomy for gastric cancer preoperatively and postoperatively. Portal and systemic blood samples were taken for the analysis of endotoxin and interleukin-6 (IL-6) concentrations during surgery in these patients. RESULTS: Although plasma endotoxin levels showed a significant increase during surgery, we did not find a correlation with ATIII, sIgA, CRP, and IL-6 levels. Systemic blood endotoxin levels during surgery correlated with a postoperative rise of serum AAT levels. Plasma ATIII levels transiently decreased on the first and third postoperative day, and sIgA levels were shown to increase on the seventh postoperative day. There was a weak relationship between the extent of postoperative endotoxemia and a reduction in ATIII concentrations. CONCLUSIONS: The influence of modest endotoxemia on postoperative antithrombin deficiency and cholestasis was limited, and increased translocational endotoxemia during abdominal surgery may be a physiological phenomenon to trigger off an acute-phase protein response.

Adult↗
PubMed2003

NPAT expression is regulated by E2F and is essential for cell cycle progression.

NPAT is an in vivo substrate of cyclin E-Cdk2 kinase and is thought to play a critical role in coordinated transcriptional activation of histone genes during the G(1)/S-phase transition and in S-phase entry in mammalian cells. Here we show that NPAT transcription is up-regulated at the G(1)/S-phase boundary in growth-stimulated cells and that the NPAT promoter responds to activation by E2F proteins. We demonstrate that endogenous E2F proteins interact with the promoter of the NPAT gene in vivo and that induced expression of E2F1 stimulates NPAT mRNA expression, supporting the idea that the expression of NPAT is regulated by E2F. Consistently, we find that the E2F sites in the NPAT promoter are required for its activation during the G(1)/S-phase transition. Moreover, we show that the expression of NPAT accelerates S-phase entry in cells released from quiescence. The inhibition of NPAT expression by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells. Thus, NPAT is an important E2F target that is required for cell cycle progression in mammalian cells. As NPAT is involved in the regulation of S-phase-specific histone gene transcription, our findings indicate that NPAT links E2F to the activation of S-phase-specific histone gene transcription.

3T3 Cells↗
PubMed2003

Different radiation susceptibility among five strains of mice detected by a skin reaction.

Published reports about skin reactions to radiotherapy, especially among breast-cancer patients, suggest that there are interindividual differences in the normal tissue response, and genetic factors are thought to be involved in this variation. An analysis of murine strain differences may reveal the mechanism of genetic factors in the extent of normal tissue damage from irradiation for several endpoints. The variation in the radiation susceptibility was observed when the skin of mice from strains A/J, C3H/HeMs, C57BL/6J, C.B.17/Icr-scid and C3H-scid was irradiated with a single dose ranging from 10 to 60 Gy, using Cs-137 gamma rays. The active skin reaction of A/J mice lasted for months. C3H/HeMs mice showed dose-dependent skin damage, and consequently recovered to a state of mild damage within 40 days after local irradiation. The time course of the response in C57BL/6J mice was shorter than in A/J mice. The 2 strains of scid mice exhibited severe damage after irradiation at any dose from 20 to 50 Gy, and did not show any dose dependency. The variation between murine strains in macroscopic and histopathological changes in skin during the progression and resolution of damage caused by irradiation suggests an inter-strain variation in the expression of genes involved in injury, apoptosis, repair, and remodeling.

Animals↗
PubMed2002

Characterization of functional regions for nuclear localization of NPAT.

NPAT plays a role in S phase entry as a substrate of cyclin E-CDK2 and activation of histone gene transcription. Although analysis of its sequence indicates that NPAT contains typical nuclear localization signals (NLS) comprising segments of positively charged amino acids, there are currently no experimental data to show that these predictive NLS are functional. To investigate whether these sequences are effective for nuclear transport of NPAT, an NPAT-green fluorescent protein fusion (NP-GFP) was constructed. After transfection of the fusion gene containing the full coding region of NPAT into cultured cells, the NP-GFP product was found exclusively in the nucleus. As expected, some deletion mutants that retained the basic amino acid clusters at the carboxyl terminus also localize the fusion protein in the nucleus. However, other fusions that lacked one of the three basic amino acid-clusters were distributed throughout the nucleus and cytoplasm. Therefore all three clusters of basic residues are necessary for localization of NPAT to the nucleus. However, another sequence outside the carboxyl terminal region functions similarly to NLS. Construction of GFP fusions with a series of truncated forms of NPAT indicated that a short peptide sequence consisting of mainly hydrophobic amino acids near the central domain of NPAT also contributes to localizing the protein in the nucleus.

Active Transport, Cell Nucleus↗
PubMed2002

[RadGenomics project].

Human health conditions are largely determined by a complex interplay among genetic susceptibility, environmental factors, and aging. The RadGenomics project, which began in April 2001, promotes analysis of genes in response to irradiation, identification of their allelic variants in the human population, development of an effective procedure for quantitating individual radio-sensitivity, and analysis of the interrelationship between genetic heterogeneity and susceptibility to irradiation. Major groups of genes with which the project will concern itself include DNA repair genes, cell cycle genes, oncogenes, tumor suppressor genes, genes for programmed cell death, genes for signal transduction, and genes for oxidative processes. The outcome of the RadGenomics project should lead to improved protocols for personalized radiotherapy and reduce the possible side effects of treatment. The project will contribute to future research on the molecular mechanisms of radiation sensitivity in humans and stimulate the development of new high-throughput technology for a broader application of the biological and medical sciences. Identification of functionally important polymorphisms in the radiation response genes may determine individual differences in sensitivity to radiation exposure. The staff members, who are specialists in a variety of fields including genome science, radiation biology, medical science, molecular biology, and bioinformatics, have come to the RadGenomics project from various universities, companies, and research institutes.

Animals↗
PubMedDate not supplied

Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor.

We investigated the effects of the farnesyl transferase inhibitor (FTI) manumycin and the MEK inhibitor PD98059 on growth of human pancreatic cancer, with mutant (SUIT2) or wild-type (BxPC-3) K-ras, xenografted into nude mice. Tumor growth was not reduced by either of the agents at a dose of 3 mg/kg without irradiation. Growth of SUIT2 irradiated at 15 Gy or 30 Gy was reduced by manumycin and PD98059: at 15 Gy, tumor volume doubling time (TVDT) increased from 18.6+/-3.8 to 36.3+/-14.2 days with PD98059 (p<0.05); at 30 Gy, TVDT increased from 32.8+/-6.8 to 70.5+/-10.5 days and 70.7+/-1.5 days, respectively. Manumycin tended to reduce growth of BxPC-3, but the difference in TVDT was not statistically significant. PD98059 significantly increased the TVDT of BxPC-3 at 30 Gy from 34.4+/-18 to 62.6+/-9.8 at 30 Gy. The present results suggest that Ras signaling pathways are potential targets for manipulation of radiosensitivity, and that induction of an alternative pathway may enhance radiosensitivity of pancreatic cancer.

Alkyl and Aryl Transferases↗