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Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 145 records · Page 8Linked to original sources
PubMed2000

Effects of perinatal nicotine exposure on development of [3H]hemicholinium-3 binding sites in rat neonate brain.

In this study, [3H]hemicholinium-3 ([3H]HC-3) binding, which labels the presynaptic high affinity-choline transport sites, was examined in two brain regions, cerebral cortex and midbrain, of nicotine-treated and -untreated rat neonates. In nicotine-untreated neonates, [3H]HC-3 binding sites of cerebral cortex increased from 64 fmol/mg protein at postnatal day 7 to 142 fmol/mg protein at postnatal day 35. In nicotine-treated neonates, the development of [3H]HC-3 binding sites in cerebral cortex was significantly retarded, compared with control neonates on the 7th, 14th and 21st postnatal days. In parallel with this, the development of muscarinic receptor in cerebral cortex, which was detected by [3H]quinuclidinyl benzylate ([3H]QNB) binding, was also retarded by nicotine treatment. However, in midbrain, neither [3H]HC-3 nor [3H]QNB binding sites at postnatal day 14 was affected by nicotine treatment. These results strongly suggest that perinatal treatment with nicotine inhibits presynaptic and postsynaptic development of the cholinergic pathway in cerebral cortex but not in midbrain of rat neonate.

Animals↗
PubMed2000

Reduced formation of granulomata in gamma(delta) T cell knockout BALB/c mice inoculated with Mycobacterium avium subsp. paratuberculosis.

The role of gamma(delta) T cells in the bovine immune response to Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) infection is poorly understood. Accordingly, using BALB/c mice that are innately susceptible to M. paratuberculosis, we compared wild-type and gamma(delta) T cell knockout BALB/c mice to study the protective roles of gamma(delta) T cells in M. paratuberculosis infection. Ten-week-old mice were inoculated intraperitoneally with either a low dose (4 x 10(6) colony-forming units [CFU]/mouse) or a high dose (4 x 10(9) CFU/mouse) of M. paratuberculosis strain ATCC 19698. Histopathologic and morphometric examinations showed reductions in the number and area of granulomatous lesions in the liver of the knockout mice at 18 weeks after inoculation with either the low or the high dose of the mycobacteria. Furthermore, at 18 weeks after inoculation, the bacterial load in the spleens of the knockout mice inoculated with the high dose was significantly lower than that of wild-type mice. No differences were found in bacterial load between the knockout and the wild-type mice in the low-dose groups. In contrast, in the livers of wild-type mice inoculated with either the low or high mycobacterial dose, increased areas of epithelioid granulomata were observed and the granulomata became disseminated widely during the experimental period. These findings in model mice suggest that gamma(delta) T cells, rather than restricting mycobacterial growth, may play a crucial role in development of epithelioid granulomata similar to those seen consistently in bovine paratuberculosis. The results of this study may have relevance to our understanding of the pathogenesis of paratuberculosis in ruminants, in which a prominent number of gamma(delta) T cells exist in the lymphoid system.

Animals↗
PubMed2000

Usefulness and safety of theophylline injection form (Theodrip) for the treatment of acute asthma.

The effects of the speed of intravenous infusion on the pharmacokinetics of theophylline were studied in 9 healthy volunteers (Ex I). Subjects were intravenously administered either six 4.8 mg/kg theophylline (Theodrip, Nikken Chemicals Co., Ltd., Japan) or three matching placebo injections (4.8 ml/kg physiological saline) for 30 min (Step I) or for 15 min (Step II). In Steps I and II, Cmax was 10.8 +/- 1.1 and 10.8 +/- 0.8 micrograms/ml, respectively. These Cmaxs were concentrations yielding therapeutic effects in patients with acute asthma. Next, comparative pharmacokinetics between theophylline (Theodrip) and aminophylline were examined by a crossover method in 16 healthy volunteers (Ex II). The 90% confidence limits of the differences of mean values were within 80-120% and were 92.8-100.1% for Cmax, 99.7-105.3% for t1/2 and 100.2-104.4% for AUC. Thus, we concluded that the pharmacokinetics of the plasma theophylline after intravenous administration of Theodrip (theophylline at 4.8 mg/kg) were bioequivalent to those of aminophylline (6.0 mg/kg) for 30 min. In Ex I and II, no subjects had adverse effects and in Ex I no influence on ECG was seen. In addition, the convenience of Theodrip was compared with that of ampules of aminophylline among nurse volunteers (Ex III). The times required for set-up of Theodrip were significantly shorter than those of aminophylline ampules. On the other hand, the adverse reactions to aminophylline resulting from hypersensitivity reactions to its ethylenediamine component have been reported. Theodrip consists of 200 mg theophylline and 200 ml physiological saline in a plastic bag. Therefore, Theodrip, which does not contain ethylenediamine, is expected to have less adverse effects and be easier to handle than aminophylline.

Acute Disease↗
PubMed2000

[Perioperative management for total en bloc spondylectomy--the effects of preoperative embolization and hypotensive anesthesia].

We retrospectively evaluated the effects of preoperative embolization and hypotensive anesthesia on total en bloc spondylectomy (TES) for solitary spinal metastases. In ten patients (treatment group), feeding arteries of spinal metastases were embolized preoperatively and controlled hypotensive anesthesia was induced during operation. In other ten patients (control group), these treatments were not applied. Intraoperative blood loss as well as the amount of blood transfused in the treatment group were significantly lower than those in the control group. Moreover, postoperative platelet counts in the treatment group were significantly higher than those in the control group. These findings indicate that embolization of feeding arteries of metastases and hypotensive anesthesia decrease intraoperative blood loss and may prevent postoperative complications in TES.

Aged↗
PubMed2000

[Mitomycin C dissolved in a reversible thermo-setting gel: effect on aqueous flare in the rabbit eye].

PURPOSE: To determine the effects of mitomycin C (MMC) dissolved in a gel, which is as effective as a higher dose of aqueous MMC solution, on aqueous flare in rabbits. METHOD: We injected subconjunctivally a 0.1 ml solution of MMC containing 30, 10, 3.0, or 0.3 micrograms of MMC dissolved in a reversible thermo-setting gel in pigmented rabbits. As a control, a 0.1 ml aqueous solution of 30 micrograms MMC was injected subconjunctivally. Aqueous flare was measured for 28 days after the injection. RESULTS: The aqueous flare in the 30 micrograms gel group was also level similar to that in the 30 micrograms aqueous solution group, but the aqueous flare in the 10, 3.0, and 0.3 micrograms gel groups was significantly lower. The increase in the aqueous flare following the administration of MMC gel was dose-dependent. CONCLUSION: The administration of MMC dissolved in a gel can diminish the ocular inflammation by reducing the dose of MMC needed for the antiproliferative effect.

Animals↗
PubMed2000

Tissue selectivity of KMD-3213, an alpha(1)-adrenoreceptor antagonist, in human prostate and vasculature.

PURPOSE: We evaluated the binding and functional affinity of KMD-3213 and other alpha 1-adrenoceptor (AR) antagonists such as prazosin or tamsulosin, to compare the tissue selectivity of these antagonists between human prostate and vasculature. MATERIALS AND METHODS: In the binding experiments, saturation experiments using [3H]-KMD and [3H]-prazosin (PZ) were performed, and competition of [3H]-PZ binding by antagonists was also examined in human prostatic and aortic membranes. In the functional study, contractile responses to noradrenaline were evaluated in human prostate and mesenteric artery. RESULTS: [3H]-PZ bound to human prostatic and aortic membranes with subnanomolar affinity. [3H]-KMD also bound to human prostate, with higher affinity than [3H]-PZ; whereas it did not bind sufficiently to human aorta. Competition of [3H]-PZ binding revealed that KMD-3213 had more than 200-fold higher affinity for human prostate than for aorta. Binding profiles of antagonists revealed that human prostate predominantly expressed alpha 1A-AR, whereas human aorta expressed alpha 1B-AR mainly. In functional experiments, KMD-3213 potently inhibited the noradrenaline-induced contraction in human prostate as potently as tamsulosin, although prazosin showed relatively low affinity. Comparing these functional affinities with those in the mesenteric artery, only KMD-3213 exhibited substantial tissue selectivity, showing more than 100-fold higher affinity for human prostate than for mesenteric artery. Functional affinity of each antagonist suggested that noradrenaline-induced contractions were mainly mediated by alpha 1L-AR in the human prostate and by alpha 1B-AR in the mesenteric artery. CONCLUSION: These results suggest that KMD-3213 is a substantially prostate-selective alpha 1-AR antagonist in human tissues compared with other alpha 1-AR antagonists.

Adrenergic alpha-Antagonists↗
PubMed1999

Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation.

Relaxation of IGF2 imprinting occurs in Wilms tumours and many other cancers, but the mechanism of loss of imprinting (LOI) remains unknown. To investigate the role of altered DNA methylation in LOI, we examined the pattern of methylation of the human insulin-IGF2 region in Wilms tumours and the normal kidney. The analysis included regions homologous to three 'differentially methylated regions' of the mouse Igf2 gene (dmrs 0, 1 and 2). In tumours displaying normal IGF2 imprinting, and in the normal kidney, maternal allele-specific DNA methylation was identified spanning exons 2 and 3. This region is homologous to dmr 0, a site of maternal-specific differential methylation in the mouse. In Wilms tumours with relaxed imprinting or 11p15.5 LOH this region was unmethylated. No other differential methylation was identified. In particular, two sites of paternal methylation in the mouse (dmrs 1 and 2), and all three imprinted IGF2 promoters were not methylated in the kidney or in Wilms tumours. We postulate that LOI in Wilms tumours is associated with loss of maternal allele-specific methylation from a region located upstream of the imprinted IGF2 promoters. This region may contain cis acting sequences that coordinately influence imprinting.

Animals↗
PubMed1999

Induction of systemic and mucosal antibody responses in mice immunized intranasally with aluminium-non-adsorbed diphtheria toxoid together with recombinant cholera toxin B subunit as an adjuvant.

Nasal mucosal immunization is very attractive for vaccination to prevent various bacterial and viral infectious diseases because of induction of systemic and mucosal immune responses. The aim of the present study was to investigate the possibility of changing the immunization procedure of diphtheria toxoid (DT) from intramuscular or subcutaneous injection to intranasal administration. Intranasal immunization with aluminium-non-adsorbed diphtheria toxoid (nDT) together with recombinant cholera toxin B subunit (rCTB, 10 microg) induced, at a concentration of 5 Lf, high levels of serum DT-specific IgG antibody responses and high or moderate levels of the specific IgA antibody responses in all mice and only a slight level of the specific IgE antibody responses in some mice. Furthermore, sufficiently high diphtheria antitoxin titres more than 0.1 international units (IU) ml(-1) were obtained from mice which showed high levels of serum DT-specific IgG antibody responses. Under the same experimental conditions, induction of significant levels of mucosal DT-specific IgA antibody responses occurred in the nasal cavity, the lung, the saliva and vaginal secretions and the small and large intestines of all mice, although there were different titres between individual mice. Similar results were also obtained with rCTB-specific serum IgG and IgA and mucosal IgA antibody responses; serum rCTB-specific IgE antibody titres were not detected. These results show that intranasal administration of nDT with rCTB must be a very useful means for vaccination against diphtheria.

Adjuvants, Immunologic↗
PubMed1999

Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences.

There has been growing interest in the role of the IRF (interferon regulatory factor) family of transcription factors in the regulation of immune responses, cytokine signaling, and oncogenesis. These members are characterized by their well-conserved DNA binding domains at the N-terminal regions. Here we report the 2.2 A resolution crystal structure of the DNA binding domain of one such family member, IRF-2, bound to DNA. The structure reveals its recognition sequence, AANNGAAA (here, recognized bases are underlined and in bold, and N indicates any base), and its cooperative binding to a tandem repeat of the GAAA core sequence induced by DNA structure distortions. These facts explain well the diverse binding properties of the IRF family members, which bind to both single and tandemly repeated sequences. Furthermore, we also identified the 'helix-hairpin-strand motif' at the C terminus of the recognition helix as a metal binding site that is commonly found in certain classes of DNA-interactive proteins. Our results provide new insights into the structure and function of this family of transcription factors.

Amino Acid Sequence↗
PubMed1999

Kainic acid-induced inducible cyclooxygenase and c-Jun phosphorylation in the rat hippocampal formation.

Inducible cyclooxygenase (COX-2) was transiently induced in the neurons throughout the entire hippocampus between 6 and 24 h after injection of kainic acid (KA). The induction of COX-2 correlated more closely with the induction of c-Jun than with that of c-Fos. Phosphorylated c-Jun was induced 6-12 h after in the CA3 pyramidal neurons, which undergo apoptosis. Almost all of neurons with phosphorylated c-Jun were colocalized with COX-2. These results suggest that COX-2 and c-Jun phosphorylation may participate in KA-induced neurodegeneration.

Animals↗
PubMed1999

Expression of p21(Cip1/Waf1/Sdi1) and p27(Kip1) cyclin-dependent kinase inhibitors during human hematopoiesis.

Expression of p21 and p27 cyclin-dependent kinase inhibitors is associated with induced differentiation and cell-cycle arrest in some hematopoietic cell lines. However, it is not clear how these inhibitors are expressed during normal hematopoiesis. We examined various human hematopoietic colonies derived from cord blood CD34(+) cells, bone marrow, and peripheral blood cells using a quantitative reverse transcription-polymerase chain reaction assay, immunochemistry, and/or Western blot analysis. p21 mRNA was expressed increasingly over time in all of the colonies examined (granulocytes, macrophages, megakaryocytes, and erythroblasts), whereas p27 mRNA levels remained low, except for erythroid bursts. Erythroid bursts expressed both p21 and p27 mRNAs with differentiation but expressed neither protein, whereas both proteins were expressed in megakaryocytes and peripheral blood monocytes. In bone marrow, p21 was immunostained almost exclusively in a subset of megakaryocytes and p27 protein was present in megakaryocytes, plasma cells, and endothelial cells. In megakaryocytes, reciprocal expression of p27 to Ki-67 was evident and an inverse relationship between p21 and Ki-67 positivities was also present, albeit less obvious. These observations suggest that a complex lineage-specific regulation is involved in p21 and p27 expression and that these inhibitors are involved in cell-cycle exit in megakaryocytes.

Adult↗
PubMed1999

Developmental expression of P-glycoprotein (multidrug resistance gene product) in the rat brain.

P-Glycoprotein (PGP), a product of the multidrug resistance gene (mdr), acts as an adenosine triphosphate-dependent drug efflux system in cells. Initially, PGP was found in cancer cells, but it is now known that PGP is richly distributed in the adult brain. Passage to the central nervous system is limited by the blood-brain barrier (BBB), and mdr1 gene-deficient mice showed up-regulation of BBB permeability. In this study, we examined the expression and localization of PGP in the rat brain during development. PGP protein was predominantly detected in the membrane fraction of the adult rat brain, although it was also faintly detected in the cytosolic fraction. PGP protein in the membrane fraction was undetectable in the embryo and early stages of postnatal development by immunoblotting studies, was first detected on postnatal day (P) 7, and then gradually increased to reach a plateau. Such changes were observed commonly in the cerebral cortex, hippocampus, and cerebellum. Immunohistochemical studies showed that PGP immunoreactivity was first detected on P7, and intense PGP immunoreactivity was observed in the adult rat brain. Double-immunolabeling studies revealed that PGP was colocalized with von Willebrand factor-immunoreactive capillaries. We further examined the colocalization of PGP and astrocytes using glial fibrillary acidic protein (GFAP) as a marker. Three-dimensional analysis showed that the GFAP-immunoreactive astrocytes possessed fine processes which ensheathed capillaries, but the PGP immunoreactivity did not colocalize with the GFAP immunoreactivity. These results indicate that PGP expression increased with postnatal development and is localized in the brain capillaries.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53.

The transcription factor IRF-1 has been implicated in tumor suppression: IRF-1 suppresses cell transformation and mediates apoptosis in vitro. Here we show that the loss of IRF-1 alleles per se has no effect on spontaneous tumor development in the mouse but dramatically exacerbates previous tumor predispositions caused by the c-Ha-ras transgene or by nullizygosity for p53. Grossly altered tumor spectrum, as compared to p53-null mice, was also observed in mice lacking both IRF-1 and p53, and cells from these mice show significantly higher mutation rate. Our results suggest that IRF-1 is a new member of the tumor susceptibility genes.

Animals↗
PubMed1999

Protein tyrosine kinase Pyk2 mediates the Jak-dependent activation of MAPK and Stat1 in IFN-gamma, but not IFN-alpha, signaling.

Two distinct types of interferon, IFN-alpha/beta and IFN-gamma, commonly exhibit antiviral activities by transmitting signals to the interior of the cell via their homologous receptors. Receptor stimulation results in the activation of distinct combinations of Janus family protein tyrosine kinases (Jak PTKs); Jak1/Tyk2 and Jak1/Jak2 for IFN-alpha/beta and IFN-gamma, respectively. Jak PTK activation by these IFNs is commonly followed by tyrosine phosphorylation of the transcription factor Stat1 at Y701, which is essential for dimerization, translocation to the nucleus and DNA-binding activity. To gain full transcriptional activity, Stat1 also requires serine phosphorylation at S727. In this paper we demonstrate that Pyk2, which belongs to another PTK family, is critical for the Jak-mediated MAPK and Stat1 activation by IFN-gamma, but not IFN-alpha. Pyk2 is selectively associated with Jak2 and activated by IFN-gamma. Overexpression of PKM, a dominant interfering form of Pyk2, in NIH 3T3 cells results in a strong inhibition of the IFN-gamma-induced activation of Erk2, serine phosphorylation of Stat1 and Stat1-dependent gene transcription. Finally, the antiviral action of IFN-gamma, but not IFN-alpha, is severely impaired by PKM overexpression. Thus, the two types of IFN may utilize distinct Jak-mediated Erk2, and possibly other MAPK activation pathways for their antiviral action.

3T3 Cells↗
PubMed1999

A new multiple myeloma cell line, MEF-1, possesses cyclin D1 overexpression and the p53 mutation.

BACKGROUND: The t(11;14)(q13;q32) translocation with cyclin D1 overexpression commonly is found in multiple myeloma (MM) and in mantle cell lymphoma (MCL). Several reports have shown that p53 mutations in MCL lead to blastoid transformation and a worse prognosis; however, the role of p53 mutations in MM with t(11;14) is unclear. METHODS: In this study the authors describe a patient with MM with t(11;14) and a p53 mutation at presentation and characterized a cell line, MEF-1, established from this patient. Immunohistochemical analysis of p53 and cyclin D1 proteins was performed. The p53 gene was analyzed by polymerase chain reaction-single strand conformation polymorphism and direct sequencing. The expression of cyclin D1 mRNA was examined by Northern blot analysis. RESULTS: MEF-1 had t(11;14) with overexpression of cyclin D1 mRNA and produced immunoglobulin kappa-light chain. MEF-1 had a mutation in exon 7 (codon 255-257) of the p53 gene, which was noted in the patient's myeloma cells. CONCLUSIONS: p53 mutations may be important genetic events in disease progression of MM with t(11;14). The MEF-1 cell line may be a useful tool to study mechanisms of progression in MM based on abnormalities of the cyclin D1 gene.

Aged↗
PubMed1999

Cutting edge: phorbol ester induction of IFN-gamma receptors leads to enhanced DR alpha gene expression.

We observed that IFN-gamma-inducible expression of the DR alpha gene was enhanced when THP-1 cells are differentiated into macrophage-like cells by phorbol ester treatment. Here, we observed that class II MHC trans-activator and STAT1 alpha mRNA, mediators of the signaling cascade from the IFN-gamma receptor to the DR alpha induction, were markedly increased by IFN-gamma stimulation in phorbol ester-activated THP-1 cells; however, both mRNAs were not increased by phorbol ester treatment alone. Then, we demonstrated that the mRNA and proteins of the IFN-gamma receptor alpha- and beta-chains were amplified by phorbol ester treatment in THP-1 cells. Consequently, these results indicate that the enhancement of DR alpha gene expression by IFN-gamma treatment in phorbol ester-activated THP-1 cells is due to the phorbol ester-induced up-regulation of IFN-gamma receptor alpha- and beta-chains. As a result, the amplification of STAT1 alpha and the increment of class II MHC trans-activator results in enhancement of DR alpha expression.

Cell Line↗
PubMed1999

Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21(waf1/cip1/sdi1) and p53.

Tranilast, which is an antiallergic drug, has a potent effect on preventing postangioplasty restenosis. To elucidate this mechanism, we studied the effect of tranilast on the proliferation of vascular smooth muscle cells (SMCs) in vitro and in vivo. Tranilast decreased the growth rate of SMCs stimulated by either 10% FBS or platelet-derived growth factor. The IC50 value, evaluated as cell number, was 100 micromol/L. These inhibitory effects were associated with inhibition of the retinoblastoma gene product (pRb) phosphorylation. Because pRb phosphorylation is regulated by cyclin-dependent kinases (CDK), we investigated CDK2 and CDK4 activities and the expression of CDK inhibitor p21(waf1/cip1/sdi1) (p21). When SMCs were stimulated by 10% FBS or platelet-derived growth factor, CDK2 and CDK4 activities reached a maximum near the G1/S transition. Tranilast suppressed their activities by >80% without reduction of CDK2/cyclin E and CDK4/cyclin D1 protein levels. These inhibitory effects were associated with enhanced expression of p21 and elevated complexing of p21 with CDK2/CDK4. Next, rat balloon-injured carotid artery was analyzed for intimal thickening and p21 expression. Tranilast-treated rats had a 70% (P<0.001) smaller neointima/media area ratio at 14 days after balloon injury compared with the controls. Immunohistochemical staining demonstrated that, in tranilast-treated rats, p21 was already present in the neointima at day 7 and strongly expressed throughout the neointima at day 14. In control rats, p21 was not observed in the neointima at day 7 but was sparsely expressed at day 14. These data demonstrate that inhibition of CDK2/CDK4 activities by the increased expression of p21 may be one mechanism by which tranilast inhibits SMC proliferation and prevents postangioplasty restenosis.

Animals↗