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T Yamaguchi

Publications and source records attributed to T Yamaguchi.

At least 109 records · Page 6Linked to original sources
PubMed2002

Ubiquitin-proteasome inhibitor enhances tumour necrosis factor-alpha-induced apoptosis in rat gastric epithelial cells.

BACKGROUND: Tumour necrosis factor (TNF-alpha) is a candidate factor for involvement in inflammation-mediated gastric mucosal injury. However, the effect of this cytokine on gastric epithelial cells has been poorly investigated. In the present study, we examined whether gastric epithelial cells are resistant to TNF-alpha-induced apoptosis, and whether this resistance is related to ubiquitin-proteasome-associated nuclear factor-kappaB (NF-kappaB) activation. METHODS: The rat gastric mucosal cell line RGM-1 was grown in DMEM/F12 medium supplemented with 10% FCS. Confluent monolayers of cells were pretreated or not for 60 min with PSI, a peptide aldehyde known to specifically inhibit the chymotrypsin-like activity of 26S proteasome. Cells were subsequently stimulated with recombinant rat TNF-alpha and their viability was determined by WST-1 assay. Apoptosis was confirmed by fluorescence microscopy after staining with Hoechst 33342 and propidium iodide, and DNA fragmentation was determined by flow cytometry using an APO-BRDU kit. IkappaB-alpha and the p65 binding subunit of NF-kappaB were detected by Western blots. RESULTS: Twenty-four-hour incubation with TNF-alpha alone or PSI alone did not affect the cell viability of RGM-1 cells. Pretreatment with PSI significantly enhanced the level of apoptosis induced by TNF-alpha. In RGM-1 cells treated with TNF-alpha, cytoplasmic IkappaB-alpha decreased and p65 in nuclear extracts increased markedly 30 min after cytokine stimulation. Pretreatment with PSI at 12.5 micromol/L blocked these TNF-alpha-induced changes. CONCLUSION: PSI enhances TNF-alpha-induced apoptosis through inhibition of NF-kappaB activation in RGM-1 cells.

Animals↗
PubMed2002

Electromyographic activity of the jaw-closing muscles during jaw opening--comparison of cases of masseter muscle contracture and TMJ closed lock.

Contracture of jaw-closing muscles is one of the causes of limitations of jaw opening. In contracture patients who have no history of trauma or infection, it is not easy to distinguish contracture from temporomandibular joint (TMJ) closed lock (TCL). The purpose of this study was to clarify whether there is any difference between electromyographic (EMG) activities of jaw muscles during jaw opening in patients with TCL and patients with masseter muscle contracture (MMC). The MMC-patient group consisted of one male and 11 females with no history of trauma or infection. The TCL-patient group consisted of one male and 11 females. Ten of the MMC patients showed certain types of EMG activities in masseter muscles (and eight in temporal muscles) during jaw opening. However, particular EMG activities were not observed in most of the TCL patients. The integral values in masseter muscles and in temporal muscles at the maximum opening position were significantly higher in the MMC-patient group than those in the TCL-patient group. These findings demonstrate that the EMG pattern of MMC patients without a history of trauma or infection is different from that of TCL patients. Therefore, EMG analysis of jaw-closing muscles during jaw opening is expected to be useful for differential diagnosis between MMC and TCL.

Adolescent↗
PubMed2002

Proportional hazards models with random effects to examine centre effects in multicentre cancer clinical trials.

In randomized clinical trials comparing treatment effects on diseases such as cancer, a multicentre trial is usually conducted to accrue the required number of patients within a reasonable period of time. The fundamental point of conducting a multicentre trial is that all participating investigators must agree to follow the common study protocol. However, even with every attempt having been made to standardize the methods for diagnosing severity of disease and evaluating response to treatment, for example, they might be applied differently at different centres, and these may vary from comprehensive cancer centres to university hospitals to community hospitals. Therefore, in multicentre trials there is likely to be some degree of variation (heterogeneity) among centres in both the baseline risks and the treatment effects. While we estimate the overall treatment effect using a summary measure such as hazard ratio and usually interpret it as an average treatment effect over the centre, it is necessary to examine the homogeneity of the observed treatment effects across centres, that is, treatment-by-centre interaction. If the data are reasonably consistent with homogeneity of the observed treatment effects across centres, a single summary measure is adequate to describe the trial results and those results will contribute to the scientific generalization, the process of synthesizing knowledge from observations. On the other hand, if heterogeneity of treatment effects is found, we should carefully interpret the trial results and investigate the reason why the variation is seen. In the analyses of multicentre trials, a random effects approach is often used to model the centre effects. In this article, we focus on the proportional hazards models with random effects to examine centre variation in the treatment effects as well as the baseline risks, and review the parameter estimation procedures, frequentist approach-penalized maximum likelihood method--and Bayesian approach--Gibbs sampling method. We also briefly review the models for bivariate responses. We present a few real data examples from the biometrical literature to highlight the issues.

Bias↗
PubMed2002

A 3D unsteady flow analysis in a doubly constricted arterial vessel.

The aim of this study is to examine the interaction between two mild atherosclerotic proliferations spaced apart by a distance S by analyzing their influence on flow structure, pressure drop and stress field in an arterial vessel under pulsatile flow conditions. This has been achieved numerically by employing a time accurate, cell centered finite volume method in solving the Navier-Stokes equations governing the 3D unsteady flow dynamics in a conceptual model of an multiply constricted arterial vessel. In comparison to the pressure drop across a single stenosis, nearly a 50% increase in the late systolic and early diastolic pressure drops has been observed across the two mild constrictions when they are spaced within a distance of S<or=4. When S<or=4, more than a 25% reduction in the peak systolic wall shear stress (WSS) on the downstream constriction is noted.

Arteries↗
PubMed2002

[Unruptured aneurysm of the noncoronary sinus of Valsalva protruded into the left atrium; report of a case].

A successful operative treatment of an unruptured aneurysm of the noncoronary sinus of Valsalva protruded into the left atrium is reported. A 64-year-old female was unexpectedly found an aneurysm of the sinus of Valsalva during the examination of bradycardia. Cardiac angiography and two dimensional echocardiography demonstrated the unruptured aneurysm of the noncoronary sinus of Valsalva of 35 mm in diameter, which protruded into the left atrium. She underwent the surgery. The aneurysm was excised and the aortic root defect was closed with a Woven dacron patch. The postoperative course was uneventful. Pathologic examination revealed the atherosclerotic change of the aorta. As far as we know, this patient is the first reported case of the unruptured aneurysm of the noncoronary sinus of Valsalva protruded into the left atrium in this country.

Aortic Aneurysm↗
PubMed2001

Comproportionation reaction and hindered rotation of coordinated pyridine rings in an acetate-bridged tetraplatinum(II) cluster with pyridine-based ligands in the cluster plane.

A series of pyridine-substituted derivatives of octaacetatotetraplatinum(II), [Pt4(CH3COO)8-n(L)2n]n+ (L= 4-dimethylaminopyridine (dmap), pyridine (py), 4-cyanopyridine (cpy); n = 1-4) were prepared, and the tetra- and octasubstituted forms (n = 2 and 4) were isolated. 1HNMR spectra showed that this type of cluster undergoes a comproportionation reaction. Reactions between clusters in which n = 0 and 2, n = 0 and 4, and n = 2 and 4 afforded Pt4 clusters with n = 1, 2, and 3, respectively, as a main product in acetonitrile. The dmap-substituted clusters, trans-[Pt4(CH3COO)6(dmap)4](ClO4)2 x 3CH3NO2 (3a(ClO4)2 x 3CH3NO2) and [Pt4(CH3COO)4(dmap)8](ClO4)4 x 4 H2O (5a(ClO4)4-4H2O), have been structurally characterized. Both 3a and 5a have a square-planar cluster core comprised of four PtII ions, and all eight out-of-plane coordination sites are occupied by acetate ligands in a bridging mode. In 5a, all of the in-plane sites are occupied by dmap ligands. In 3a, four dmap ligands occupy the coordination sites at the two mutually opposite edges of the square planar cluster skeleton, giving a trans tetrasubstituted form of [Pt4(CH3COO)8-] (1). In octasubstituted 5a, adjacent dmap ligands are so closely arranged that the Pt-N distances (2.20(3), 2.30(3) A) are longer than those in tetrasubstituted 3a (2.13(1), 2.15(1) A) and related Pt4 clusters. Furthermore, rotation of the dmap ligand about the Pt-N bond in 5a was restricted, and the rate constant of the rotation was 4.5s(-1) at 20 degrees C from dynamic NMR study. Cluster [Pt4(CH3COO)5(dmap)6]3+ (4a) also exhibited similar hindered rotation with the rate constants of 2.0s(-1), 12s(-1) and approximately 10(4)s(-1) at 20 degrees C depending on the coordination sites of the dmap ligands in 4a.

Journal Article↗
PubMed2001

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to screen for changes in the number of DNA sequence copies in 30 primary colorectal cancers and 16 liver metastases, to identify regions that contain genes important for the development and progression of colorectal cancer. In primary colorectal cancer, we found frequent gains at 7p21 (36.7%), 7q31-36 (30%), 8q23-24 (43.0%), 12p (30%), 14q24-32 (33.3%), 16p (40.0%), 20p (33.3%), 20q (63.3%) and 21q (36.3%), while loss was often noted at 18q12-23 (36.7%). In metastatic tumors, there were significantly more gains and losses of DNA sequences than in primary tumors, with gains at 8q23-24 (found in 62.5% of recurrences vs. 43.0% of primary tumors), 15q21-26 (37.5% vs. 20.0%), 19p (43.8% vs. 20.0%) and 20q (81.3% vs. 63.3%) and losses at 18q12-23 (50.0% vs. 36.7%). The pattern of genetic changes seen in metastatic tumors, with frequent gains at 8q23-24 and 20q and loss at 18q12-23, suggests the progression of colorectal cancer. We investigated a clinical follow-up study for all patients examined by CGH and directed our attention to the genetic changes consisting of gains at 8q and 20q. The incidence of liver metastases was higher in patients with primary colorectal cancer with these genetic changes. Gains at 8q and 20q might be useful to identify patients at high risk for developing liver metastases.

Chromosome Aberrations↗
PubMed2001

Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells.

IL-18, a potent IFN-gamma-inducing cytokine, is expressed by various nonimmune cells as well as macrophages, suggesting that it has important physiological and immunological roles. The present study focused on the mechanism of active IL-18 induction from human oral epithelial cells. The epithelial cells and the cell lines constitutively express IL-18 mRNA and the 24-kDa precursor form of IL-18. Bioactive IL-18 exhibiting IFN-gamma-inducing activity was detected in the supernatant of the cells on costimulation with neutrophil proteinase 3 (PR3) and LPS for 24 h after IFN-gamma-priming for 3 days. An active 18-kDa form of IL-18 was detected in lysate and supernatant of the cells only after the above treatment and the induction was inhibited by cycloheximide and by serine proteinase inhibitors. After the treatment, lactate dehydrogenase activity was not detected in the cell culture supernatant, and PR3 was detected only in the membrane and not in cytoplasm fractions of the cells. Caspase-1 was not detected in the cells even after the treatment and the IL-18 induction was not inhibited by a caspase-1 inhibitor. These results suggest that the PR3-mediated induction of bioactive IL-18 secretion from oral epithelial cells in combination with LPS after IFN-gamma-priming occurred via a caspase-1-independent pathway, and provide new insight into the possible involvement of a neutrophil proteinase in the induction of bioactive IL-18 in oral inflammation such as periodontitis.

Adult↗
PubMed2001

p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint.

A recently identified ribonucleotide reductase (RR), p53R2, is directly regulated by p53 for supplying nucleotides to repair damaged DNA. We examined the role of this p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint, comparing it to R2-dependent DNA synthesis. The elevation of DNA synthesis activity through RR in response to gamma-irradiation was closely correlated with the level of expression of p53R2 but not of R2. The p53R2 product accumulated in nuclei, whereas R2 levels in cytoplasm decreased. We found a point mutation of p53R2 in cancer cell line HCT116, which resulted in loss of RR activity. In those cells, DNA damage-inducible apoptotic cell death was enhanced through transcriptional activation of p53AIP1. The results suggest that p53R2-dependent DNA synthesis plays a pivotal role in cell survival by repairing damaged DNA in the nucleus and that dysfunction of this pathway might result in activation of p53-dependent apoptosis to eliminate dangerous cells.

Cell Cycle↗
PubMed2001

Resonance induced pacemakers: a new class of organizing centers for wave propagation in excitable media.

Propagation of waves in an extended excitable system is considered. It is shown that traveling wave fronts can be triggered and maintained via local periodic modulations of an appropriate system parameter. For a finite range of perturbation frequencies, this new class of pacemakers introduces spatiotemporal self-organization in an otherwise quiescent medium. Excitation waves of activity similar to those observed in heart tissue cultures and other biological preparations can emerge in the presence of these pacemakers.

Biological Clocks↗
PubMed2001

A novel 5-HT3 receptor agonist, YM-31636, increases gastrointestinal motility without increasing abdominal pain.

We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a novel 5-HT3 receptor agonist, on gastrointestinal functions including visceral pain reflex in rats. Injection of YM-31636 increased the number of fecal pellets. This effect was completely inhibited by ramosetron, a 5-HT3 receptor antagonist. YM-31636 also increased the intracolonic pressure measured in both conscious and anesthetized rats. In isolated distal colon, YM-31636 increased the short-circuit current response. This effect was abolished by ramosetron. Both the maximal response and the potency of YM-31636 were weaker than those of other 5-HT3 receptor agonists. In two visceral pain reflex models, YM-31636 neither changed the magnitude of pressor response to colonic distension in anesthetized rats nor affected the visceromotor threshold to colorectal distension in conscious rats. In conclusion, YM-31636 facilitated defecation without increasing visceral pain. Consequently, 5-HT3 receptor agonists like YM-31636 would be promising in the treatment of chronic constipation.

Abdominal Pain↗
PubMed2001

Involvement of Rho-kinase in vascular remodeling caused by long-term inhibition of nitric oxide synthesis in rats.

Long-term inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular remodeling in rats. To determine the pathogenic mechanism involved in vascular remodeling, we examined the effects of fasudil, a Rho-kinase inhibitor, on vascular lesion formation. In rats treated with L-NAME at 10 mg/kg/day, vascular remodeling was evident in both large and small coronary arteries at the fourth week. Fasudil (3 mg/kg, p.o., twice daily) markedly prevented the development of vascular remodeling in small coronary arteries. Coronary flow was measured in Langendorff perfused isolated heart preparations. Long-term treatment with L-NAME caused a significant decrease in coronary flow, which was significantly inhibited by fasudil. Fasudil suppressed the structural and functional changes in coronary arteries by chronic blockade of NO synthesis. Thus, the Rho-kinase pathway may be substantially involved in the pathogenesis of vascular remodeling in this rat model.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Modulation of fish phagocytic cells by N-terminal peptides of proopiomelanocortin (NPP).

N-terminal peptide of proopiomelanocortin (NPP, or pro-gamma-MSH) has shown to exhibit biological activity such as stimulation of adrenal mitogenesis and prolactin release-inhibiting factor activity. Structurally, studies reveal a significant difference between fish NPP from that of tetrapods, as NPPs from carp and salmonid lack gamma-MSH. Thus, fish NPP may exhibit functions different from that of mammals. The activation of phagocytic cells by NPP was analysed using rainbow trout Oncorhynchus mykiss and carp Cyprinus carpio. Rainbow trout and carp macrophages incubated with chum salmon NPP significantly enhanced the production of superoxide anion in comparison with control macrophages (without hormones). Both rainbow trout and carp macrophages had shown increased phagocytosis when stimulated administered with NPP. The above results were complemented by in vivo studies where NPP was administered to rainbow trout and carp. NPP significantly increased superoxide anion production as well as phagocytosis in macrophages. These results show that NPP in lower vertebrates activates the function of the phagocytic cells.

Animals↗
PubMed2001

Prevalence of Rho-inactivating epidermal cell differentiation inhibitor toxins in clinical Staphylococcus aureus isolates.

Staphylococcus aureus produces exotoxins of the epidermal cell differentiation inhibitor (EDIN) family that ADP-ribosylate and inactivate Rho GTPases. The prevalence of genes encoding EDIN in clinical and nasal isolates of S. aureus was investigated. Of the 196 clinical S. aureus isolates tested, 15 (7.8%) were positive for 1 edin gene, whereas of 81 nasal isolates tested, only 3 (3.7%) were edin positive. Of the total 18 edin-positive isolates, 16 (90%) carried edin-B and 2 (10%) carried edin-C, but none was positive for edin-A. All edin-positive strains could produce the respective EDIN protein. Pulsed-field gel electrophoresis analysis suggested that the edin-B-positive S. aureus isolates are derived from one clone, and the edin-C-positive isolates are derived from another clone. Given that toxins acting on Rho GTPases are considered to be important for bacterial virulence, the EDIN toxins of S. aureus should receive more attention in future studies.

Adult↗
PubMed2001

Endogenous cannabinoid, 2-arachidonoylglycerol, attenuates naloxone-precipitated withdrawal signs in morphine-dependent mice.

In the present study, we examined the effects of endogenous ligand 2-arachidonoylglycerol (2-AG) on naloxone-precipitated withdrawal in morphine-dependent mice, in comparison with that of two cannabinoid agonists, an ingredient of Cannabis sativa Delta(8)-tetrahydrocannabinol (Delta(8)-THC) and the synthetic cannabinoid CB1 receptor agonist HU-210. 2-AG at a dose of 10 microg per mouse (i.c.v.) significantly inhibited both jumping and forepaw tremor as signs of withdrawal following naloxone challenge in morphine-dependent mice. Furthermore, both Delta(8)-THC and HU-210 significantly attenuated these symptoms of withdrawal in morphine-dependent mice. Therefore, it is suggested that inactivation of the endogenous cannabinoid system is related to the induction of withdrawal syndrome in morphine-dependent mice. Moreover, hyperlocomotor activity in morphine-dependent mice was markedly increased by Delta(8)-THC 10 mg/kg, which had no effect in naive mice. This finding suggested that in morphine dependence, upregulation of cannabinoid CB1 receptors occurred. Non-psychoactive CB1 receptor agonists or accelerators of endocannabinoid synthesis may be potential as therapeutic drugs for opiate withdrawal symptoms.

Animals↗
PubMed2001

A comparison of gene expression in murine cardiac allografts and isografts by means DNA microarray analysis.

BACKGROUND: Acute rejection of allografts remains a significant problem in clinical transplantation, and the fundamental mechanism underlying this rejection are as yet only poorly elucidated. Recently, DNA microarrays have come into use for the study of gene expression profiles, and we have taken advantage of this new technology to investigate acute rejection. We compared mRNA profiles in murine cardiac allografts with isografts using DNA microarrays with probe sets corresponding to more than 11,000 mice genes. METHODS: We screened for gene expression changes in murine cardiac allografts between fully incompatible mice strains (BALB/c H2d to C3H/He H2k) using a DNA microarray. The heart was heterotopically transplanted. Allografts (BALB/c to C3H/He) were removed on days 1, 3, and 5. As a control, isografts (C3H/He to C3H/He) harvested on days 1, 3, and 5 and native hearts of both strain mice (C3H/He and BALB/c) were obtained. RESULTS: On day 5, interferon-gamma (IFN-gamma) and many IFN-gamma-inducible genes were profoundly induced in the allograft relative to isograft. Monokine induced by IFN-gamma was most profoundly induced followed by inducibly expressed GTPase and Lmp-2. IFN-gamma was also profoundly induced. The induction was detectable from day 3. In contrast, genes regulated by other cytokines exhibited only modest changes. CONCLUSION: IFN-gamma-inducible genes are specifically up-regulated in murine cardiac allografts, suggesting that signaling mediated by IFN-gamma may play an important role in the late phase of acute rejection in vivo.

Animals↗