PubMed Health⌕ Search

Biomedical subjects

Takahiro Suzuki

Publications and source records attributed to Takahiro Suzuki.

At least 19 recordsLinked to original sources
PubMed2007

Natural killer cell-mediated ablation of metastatic liver tumors by hydrodynamic injection of IFNalpha gene to mice.

Interferon (IFN) alpha is a pleiotropic cytokine acting as an antiviral substance, cell growth inhibitor and immunomodulator. To evaluate the therapeutic efficacy and mechanisms of IFNalpha on hepatic metastasis of tumor cells, we hydrodynamically injected naked plasmid DNA encoding IFNalpha1 (pCMV-IFNa1) into Balb/cA mice having 2 days hepatic metastasis of CT-26 cells. Single injection of pCMV-IFNa1 efficiently enhanced the natural killer (NK) activity of hepatic mononuclear cells, induced production of IFNgamma in serum and led to complete rejection of tumors in the liver. Mice protected from hepatic metastasis by IFNalpha therapy displayed a tumor-specific cytotoxic T cell response and were resistant to subcutaneous challenge of CT-26 cells. NK cells were critically required for IFNalpha-mediated rejection of hepatic metastasis, because their depletion by injecting anti-asialo GM1 antibody completely abolished the antimetastatic effect. To find whether NK cells are directly activated by IFNalpha and are sufficient for the antimetastatic effect, the responses to IFNalpha were examined in SCID mice lacking T cells, B cells and NKT cells. IFNalpha completely rejected hepatic metastasis in SCID mice and efficiently activated SCID mononuclear cells, as evidenced by activation of STAT1 and a variety of genes, such as MHC class I, granzyme B, tumor necrosis factor-related apoptosis-inducing ligand and IFNgamma, and also enhanced Yac1 lytic ability. Study of IFNgamma knockout mice revealed that IFNgamma was not necessary for IFNalpha-mediated NK cell activation and metastasis protection. In conclusion, IFNalpha efficiently activates both innate and adaptive immune responses, but NK cells are critically required and sufficient for IFNalpha-mediated initial rejection of hepatic metastasis of microdisseminated tumors.

Animals↗
PubMed2006

Metabolic profiles in ovulatory and anovulatory primiparous dairy cows during the first follicular wave postpartum.

Metabolic hormones affect ovarian function in the cow. However, the relationship between metabolic factors and ovarian function is not clear in the postpartum primiparous cow because they are still growing. The aim of the present study was to investigate in detail the time-dependent profile of the metabolic hormones, metabolites, and milk yields of ovulatory and anovulatory primiparous cows during the first follicular wave postpartum. We used 16 primiparous Holstein cows and obtained blood samples for the profiles of metabolites (glucose; non-esterified fatty acid, NEFA; ketone body; total cholesterol; and aspartate aminotransferase), metabolic hormones (growth hormone, GH; insulin-like growth factor-I, IGF-1; and insulin), and progesterone every other day from 1 to 21 days postpartum. In addition, all ovaries were observed using ultrasound. Dairy milk yield was recorded during the experimental period. In all cows, the first follicular wave postpartum was observed and 6 of the cows ovulated. The plasma glucose (P<0.0001) and IGF-1 (P<0.001) concentrations were lower and the plasma NEFA (P<0.0001) and ketone bodies (P<0.0001) concentrations and daily milk yield (P<0.0001) were higher in the anovulatory cows compared to the ovulatory cows. However, the GH levels, which enhance lipolysis for milk production, insulin and other metabolites did not differ between the two groups. In conclusion, the present study suggests that anovulation of the dominant follicle during the first follicular wave postpartum in primiparous cows is induced by low IGF-1 levels that are similar to those of multiparous cows. In addition, anovulatory cows are likely to mobilize body fat stores for milk production more easily than ovulatory cows.

Animals↗
PubMed2006

Highly efficient ex vivo expansion of human hematopoietic stem cells using Delta1-Fc chimeric protein.

Ex vivo expansion of hematopoietic stem cells (HSCs) has been explored in the fields of stem cell biology, gene therapy, and clinical transplantation. Here, we demonstrate efficient ex vivo expansion of HSCs measured by long-term severe combined immunodeficient (SCID) repopulating cells (SRCs) from human cord blood CD133-sorted cells using a soluble form of Delta1. After a 3-week culture on immobilized Delta1 supplemented with stem cell factor, thrombopoietin, Flt-3 ligand, interleukin (IL)-3, and IL-6/soluble IL-6 receptor chimeric protein (FP6) in a serum- and stromal cell-free condition, we achieved approximately sixfold expansion of SRCs when evaluated by limiting dilution/transplantation assays. The maintenance of full multipotency and self-renewal capacity during culture was confirmed by transplantation to nonobese diabetic/SCID/gammac(null) mice, which showed myeloid, B, T, and natural killer cells as well as CD133(+)CD34(+) cells, and hematopoietic reconstitution in the secondary recipients. Interestingly, the CD133-sorted cells contained approximately 4.5 times more SRCs than the CD34-sorted cells. The present study provides a promising method to expand HSCs and encourages future trials on clinical transplantation.

AC133 Antigen↗
PubMed2006

Histone H3 acetylated at lysine 9 in promoter is associated with low nucleosome density in the vicinity of transcription start site in human cell.

Nucleosome depletion in the promoters has been indicated in yeasts, suggesting that nucleosome depletion in promoter might be a fundamental feature of eukaryotic transcriptional regulation. We compared the relationship between histone H3 acetylation at lysine 9 (K9) in promoter, gene expression level, and nucleosome density in the vicinity of the transcription start site (TSS), in HepG2 cells (human hepatocellular liver carcinoma cells). We found that the density of nucleosome is relatively low in the close vicinity of TSS flanked by H3 K9 significantly acetylated promoter, compared with that for genes without marked H3 K9 acetylation in promoter, regardless of their transcriptional activation status. Our results imply that the relative nucleosome depletion in the vicinity of TSS is not necessarily associated with active transcription, but with histone H3 K9 acetylation in promoter.

Acetylation↗
PubMed2006

Abnormal placental cord insertion may induce intrauterine growth restriction in IVF-twin pregnancies.

BACKGROUND: This study determined whether twins conceived through assisted reproduction technology (ART) have an increased risk of perinatal complications compared with natural twin pregnancies and investigated potential associated major risk factors. METHODS: This retrospective study consisted of 199 twins born between 1994 and 2003. There were four groups according to conception modalities: 97 twins after spontaneous pregnancy, 24 after induced ovulation, 28 after intrauterine insemination (IUI) and 50 after IVF with embryo transfer. Analysis included preterm birth, Caesarean delivery, weight discordance, intrauterine growth restriction (IUGR), low-birth-weight, Apgar score, chorionicity, gross placental pathology and placental umbilical cord insertion (UCI) site. RESULTS: A significant difference was found in IUGR between the IVF group (7.0%) and spontaneous pregnancy group (14.9%). When maternal age was >30 years there was a 2.86-fold increase in the risk of IUGR. There was a 3.69-fold increased risk of IUGR in the presence of abnormal UCI (odds ratio 3.69, 95% CI 1.62-8.42) and a 2.18-fold increased risk of abnormal UCI in monochorionic twins when compared with dichorionic twins (odds ratio 2.18, 95% CI 1.30-3.66). CONCLUSION: Twins conceived through ART are not at an increased risk of perinatal complications. A relationship has been found between abnormal UCI and IUGR.

Diseases in Twins↗
PubMed2006

Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem cell transplantation using in vivo alemtuzumab with or without CD52-positive malignancies.

We recently reported that the addition of in vivo alemtuzumab to the conditioning regimen enables 2- or 3-locus-mismatched hematopoietic stem cell transplantation without an excessive risk of graft rejection or graft-versus-host disease. In a later series of patients, however, one patient with refractory chronic lymphocytic leukemia with large residual tumors at transplantation developed graft rejection. While the peak alemtuzumab concentration in the previous patients without graft rejection was higher than 5 micro g/ml, the peak alemtuzumab concentration in this patient was only 1.44 micro g/ml. We considered that alemtuzumab was bound to the large residual tumors, which resulted in a low blood concentration of alemtuzumab. Therefore, it is important to debulk tumors before the conditioning regimen for patients with refractory CD52-positive hematological malignancies, or the dose of alemtuzumab should be adjusted by monitoring the blood concentration, when alemtuzumab is used for in vivo T-cell depletion in 2- or 3-locus-mismatched transplantation.

Alemtuzumab↗
PubMed2006

Evidence for activation of nuclear factor kappaB in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis, and atherosclerosis evolves from activation of the inflammatory cascade. We propose that activation of the nuclear factor kappaB (NF-kappaB), a key transcription factor in the inflammatory cascade, occurs in OSA. Nine age-matched, nonsmoking, and non-hypertensive men with OSA symptoms and seven similar healthy subjects were recruited for standard polysomnography followed by the collection of blood samples for monocyte nuclear p65 concentrations (OSA and healthy groups). In the OSA group, p65 and of monocyte production of tumor necrosis factor alpha (TNF-alpha) were measured at the same time and after the next night of continuous positive airway pressure (CPAP). p65 Concentrations in the OSA group were significantly higher than in the control group [median, 0.037 ng/microl (interquartile range, 0.034 to 0.051) vs 0.019 ng/microl (interquartile range, 0.013 to 0.032); p = 0.008], and in the OSA group were significantly correlated with apnea-hypopnea index and time spent below an oxygen saturation of 90% (r = 0.77 and 0.88, respectively) after adjustment for age and BMI. One night of CPAP resulted in a reduction in p65 [to 0.020 ng/mul (interquartile range, 0.010 to 0.036), p = 0.04] and levels of TNF-alpha production in cultured monocytes [16.26 (interquartile range, 7.75 to 24.85) to 7.59 ng/ml (interquartile range, 5.19 to 12.95), p = 0.01]. NF-kappaB activation occurs with sleep-disordered breathing. Such activation of NF-kappaB may contribute to the pathogenesis of atherosclerosis in OSA patients.

Adult↗
PubMed2006

Gene expression profiling in biliary epithelial cells of primary biliary cirrhosis using laser capture microdissection and cDNA microarray.

UNLABELLED: Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver disease characterized by progressive destruction of interlobular bile ducts that leads to biliary cirrhosis. To elucidate the etiology of PBC, the gene expression profile in biliary epithelial cells (BECs) was analyzed. Liver specimens of 5 PBC, 3 chronic hepatitis C (CHC), and 3 normal subjects were obtained. BECs were selectively collected by laser capture microdissection (LCM), RNA were obtained by extraction and amplification with T7 RNA polymerase, and a cDNA microarray analysis was performed. The following genes exhibited increased expression in BEC of PBC, as compared with CHC or normal subjects: human leukocyte antigen DQ alpha 1 (HLA-DQA-1), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and vascular cell adhesion molecule 1 (VCAM-1). The immunohistochemistry for HLA-DQA-1, CEACAM1, TRAIL, and VCAM-1 confirmed these results. Furthermore, two-way cluster analysis showed that the gene expression profiling in BEC of PBC were categorized into a separate cluster, distinct from CHC or normal subjects. CONCLUSIONS: The gene expression profiling in BEC of PBC differed from those of CHC and normal subjects, and the genes concerning local immune response, such as HLA-DQA-1, CEACAM1, TRAIL, and VCAM-1, exhibited increased expression, indicating that they were involved in the development of bile duct injury.

Adult↗
PubMed2006

IgG-antiphospholipid antibodies in follicular fluid of IVF-ET patients are related to low fertilization rate of their oocytes.

PROBLEM: Patients undergoing in vitro fertilization and embryo transfer (IVF-ET) failures show an increased incidence of antiphospholipid antibodies (aPL) in their blood. The physiological manifestations of aPL in this patient group are nonetheless controversial. Pathological effects of aPL on embryos in vitro have been documented. We questioned whether aPL if found in follicular fluids (FFs) could result in embryonic damage. METHOD OF STUDY: Blood from 44 patients with three or more IVF-ET failures were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of immunoglobulin (Ig)G, IgM and IgA aPL. Both the 29 aPL-positive and 15 aPL-negative patients gave permission for FF collection during their next IVF-ET attempt for additional aPL determinations. RESULTS: Patients with no aPL in their blood, had no aPL in their FFs. Patients with IgG and/or IgM aPL in their blood had IgG but not IgM in their respective FFs. CONCLUSIONS: The presence of IgG aPL in FFs and increased infertility length were significantly related to lower fertilization rates, independently. Follicular fluid IgG aPL appears as a risk factor in association with successful IVF-ET outcomes.

Adult↗
PubMed2006

Simultaneous monitoring method of polycyclic aromatic hydrocarbons and persistent organic pollutants in the atmosphere using activated carbon fiber filter paper.

In order to simultaneously monitor the concentrations of PAHs and POPs in the atmosphere, an activated carbon fiber filter paper (ACFP) was used as the adsorbing material in this study. The pressurized liquid extraction method (PLE method) was used to extract PAHs and POPs collected on the ACFP. Toluene was an effective solvent to extract them from ACFP using the PLE method, but some of PAHs, such as benzo(a)pyrene, benzo(g,h,i)perylene, dibenzo(a,h)anthracene and indeno(1,2,3-cd)pyrene, were hardly extracted. These PAHs were adsorbed on the particulate matter in the atmosphere. In general, these forms of particulate matter could be collected using a quartz fiber paper (QFP); these PAHs were efficiently extracted from the QFP using the PLE method with toluene. In this study, the collecting method of the PAHs was modified by using QFP overlapped in front of the ACFP. Atmospheric monitoring of PAHs and POPs in Niigata area was performed using this method, and most of the target compounds were detected. However, some of the POPs, such as aldrin, endrin, mirex, could not be detected. The POPs, such as hexachlorobenzene, alpha-hexachlorocyclohexane and chlordanes, and most of the PAHs were detected from all of the samples collected throughout the monitoring period. It was confirmed that these methods were effective to simultaneously monitor the concentrations of the PAHs and POPs in the atmosphere.

Journal Article↗
PubMed2006

[Adsorption of local anesthetic into disposable infusion balloon].

BACKGROUND: The aim of this study was to investigate the adsorption of local anesthetics lidocaine and ropivacaine, into disposable infusion balloons made from various kinds of plastics. METHODS: The concentration of local anesthetic that flows out of a balloon was measured. RESULTS: The concentration of both lidocaine and ropivacaine in clinical formula decreased only 4.5 percent regardless of infusion balloons. However, the concentration of lidocaine pH 7.4 decreased by 10 percent in the Syrinjector made from polypropylene and polyvinyl chloride, and that of 18-20 percent in other infusion balloons (Surefuser, Baxtor Infuser, DIB Catheter made from isoprene rubber and polyvinyl chloride, isoprene rubber and polyvinyl chloride, silicon and polyvinyl chloride, respectively). CONCLUSIONS: The adsorption of local anesthetic into infusion balloons has little effect in clinical situation. Whereas, in case of lidocaine pH 7.4, the adsorption depends on the specific type of plastics.

Adsorption↗
PubMed2006

[Neuromuscular blocking effects, pharmacokinetics and safety of Org 9426 (rocuronium bromide) in Japanese patients].

BACKGROUND: The purpose of this study was to examine pharmacodynamics, pharmacokinetics and safety of Org 9426 (rocuronium bromide) in Japanese patients. METHODS: Seventy-eight patients anesthetized with thiopental, droperidol, fentanyl and nitrous oxide, were randomized to receive either a single dose of Org 9426 0.3 mg x kg(-1), 0.6 mg x kg(-1) or 0.9 mg x kg(-1). Contraction of the adductor pollicis to the ulnar nerve stimulation (0.1 Hz) was measured by acceleromyography. Blood was sampled over 6 hr and pharmacokinetic variables were calculated by plasma concentrations of Org 9426. RESULTS: Onset times for patients receiving 0.3 mg x kg(-1), 0.6 mg x kg(-1) or 0.9 mg x kg(-1) were 271.5 s, 140.0s and 125.4s, respectively. There was a dose-dependent increase in clinical durations until 25% recovery of twitch height (17.4 min in 0.3 mg x kg(-1) group, 37.2 min in 0.6 mg x kg(-1) and 60.4 min in 0.9 mg x kg(-1) group). Pharmacokinetic study revealed that elimination half life, steady state volume of distribution and plasma clearance of Org 9426 were 48-76 min, 146-181 ml x kg(-1), and 3.8-4.5 ml x min(-1) x kg(-1), respectively. No adverse effects were found except a case of local erythema on a forearm. CONCLUSIONS: The efficacy of neuromuscular block, stable pharmacokinetic behavior and excellent safety of Org 9426 were also confirmed in Japanese surgical patients.

Adult↗
PubMed2006

[Sugammadex (Org 25969, modified gamma-cyclodextrin)].

Sugammadex, a chemically modified gamma-cyclodextrin, was synthesized as a selective reversal agent for rocuronium, a steroidal neuromuscular blocking agent. The lipophilic cavity of sugammadex molecule encapsulates the lipophilic steroid rings of rocuronium and forms 1:1 host-guest complex. Additionally, negatively charged carboxyl groups around the rim of cyclic sugammadex easily attract a positively charged quaternary nitrogen of rocuronium. When sugammadex 8 mg x kg(-1) was given intravenously during a profound block induced by rocuronium, a train-of-four ratio of the thenar muscle to the ulnar nerve stimulation returned to 0.9 within 2 min. The rapid reversal can be explained by the rapid redistribution of free rocuronium from the neuromuscular junction to the plasma. The reversal effects are not influenced by anesthetics. There is no interaction with cholinergic systems. Therefore, undesired side effects attendant with anticholinesterases are not seen. No recurarization was also observed. The majority of the complexes is excreted via the kidney, but the reversal effects are complete even in patients with renal failure.

Cholinergic Antagonists↗
PubMed2005

Crk-associated substrate lymphocyte type is required for lymphocyte trafficking and marginal zone B cell maintenance.

The lymphocyte-specific Cas family protein Cas-L (Crk-associated substrate lymphocyte type) has been implicated to function in lymphocyte movement, mediated mainly by integrin signaling. However, its physiological role is poorly understood. In this study we analyzed the function of Cas-L in lymphocytes using gene-targeted mice. The mutant mice showed a deficit of marginal zone B (MZB) cells and a decrease of cell number in secondary lymphoid organs. An insufficient chemotactic response and perturbed cell adhesion were observed in Cas-L-deficient lymphocytes, suggesting that the aberrant localization was responsible for the deficit of MZB cells. Moreover, we found that lymphocyte trafficking was altered in Cas-L-deficient mice, which gave a potential reason for contraction of secondary lymphoid tissues. Thus, Cas-L affects homeostasis of MZB cells and peripheral lymphoid organs, which is considered to be relevant to impaired lymphocyte migration and adhesion.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Viral covalently closed circular DNA in a non-transgenic mouse model for chronic hepatitis B virus replication.

BACKGROUND/AIMS: The lack of small animal models supporting chronic hepatitis B virus (HBV) infection impedes the assessment of anti-viral drugs in the whole animal. Although transgenic mice have been used for this purpose, these models are clearly different from natural infection, because HBV is produced from the integrated HBV sequence harbored in all hepatocytes. METHODS: Balb/cA nude mice were hydrodynamically injected with a plasmid having 1.5-fold over-length of HBV DNA and analyzed for HBV replication. RESULTS: Hydrodynamically injected mice showed substantial levels of antigenemia and viremia for more than 1 year. Covalently closed circular DNA (cccDNA), the template of viral replication in natural infection, was produced in the livers and was critically involved in the long-term HBV production, because disruption of the pol gene of the inoculated DNA resulted in transient expression of HBV genes for less than 2 months. Administration of the IFNalpha gene transiently suppressed HBV DNA replication, but was not capable of eliminating HBV in this model. CONCLUSIONS: In vivo gene transfer of a plasmid encoding HBV DNA can establish chronic viral replication in mice, which involves, at least in part, new synthesis of the HBV cccDNA episome, thus recapitulating a part of human HBV infection.

Animals↗
PubMed2005

Comparative analysis of expression of histone H2a genes in mouse.

BACKGROUND: At least 18 replication-dependent histone H2a genes are distributed in 3 Hist gene clusters on different chromosomes of the mouse genome. In this analysis we designed specific PCR primers for each histone H2a transcript and studied the expression levels and patterns using quantitative RT-PCR (qRT-PCR). In addition, we compared histone H3 K9 acetylation levels in the promoter regions of H2a genes by ChIP (chromatin immunoprecipitation)--quantitative PCR (qPCR) analysis. RESULTS: RT-PCR analysis indicated that all 20 histone H2a genes assessed in this study are expressed. The replication-dependent histone H2a genes have different expression levels but similar expression patterns. Among the 20 histone H2a genes, the expression-level of H2afz, a replication-independent gene, was highest, and that of Hist1h2aa, a replication-dependent gene, was lowest. Among 18 replication-dependent H2a genes, the expression level of Hist3h2a was highest. The ChIP-qPCR analysis showed that histone H3 K9 acetylation levels in promoter regions of both H2afz and Hist3h2a are clearly higher than that in the promoter region of Hist1h2aa. The H3 K9 acetylation level in the promoter of Hist1h2aa is similar to that in the gamma-satellite region. CONCLUSION: These results strongly suggest that histone H3 K9 acetylation plays a role in the expression of histone genes.

Acetylation↗