Biomedical subjects

T Itoh

Publications and source records attributed to T Itoh.

At least 289 records · Page 16Linked to original sources

PubMed1999

Effect of extract prepared from the roots of Paeonia lactiflora on endothelium-dependent relaxation and antioxidant enzyme activity in rats administered high-fat diet.

This study examined the effect of Paeoniae Radix (PR) on endothelial function and the activity of superoxide dismutase (SOD) of erythrocytes in rats administered a high-fat diet. Administration of the extract of PR increased the endothelium-dependent relaxation and the activities of SOD compared with high the cholesterol diet group significantly. Hypercholesterolaemia induced an increase of endothelial superoxide anion and endothelial dysfunction. Paeoniae Radix is suggested to have a protective effect on endothelial cells and their function.

Animals↗

PubMed1999

Almost pure I(alpha) cellulose in the cell wall of Glaucocystis.

Crystalline features of cellulose microfibrils in the cell walls of Glaucocystis (Glaucophyta) were studied by combined spectroscopy and diffraction techniques, and the results were compared with those of Oocystis (Chlorophyta). Although these algae are grouped into two different classes, by the composition of their chloroplasts for instance, their cell walls are quite similar in size and morphology. The most striking features of their cellulose crystallites are that they have the highest cellulose I(alpha) contents reported to date. In particular, the I(alpha) fraction of cellulose from Glaucocystis was found to be as high as 90% from (13)C NMR analysis. The mode of preferential orientation of cellulose crystallites in their cell walls is also interesting; equatorial 0.53-nm lattice planes were oriented parallel to the cell surface in the case of Glaucocystis, while the 0.62-nm planes were parallel to the Oocystis cell surface. Such a structural variation provides another link to the evolution of cellulose structure, biosynthesis, and its biocrystallization mechanism.

Cell Wall↗

PubMed1999

Deaths from heat-stroke in Japan: 1968-1994.

Global warming is increasingly recognized as a threat to the survival of human beings, because it could cause a serious increase in the occurrence of diseases due to environmental heat during intermittent hot weather. To assess the direct impact of extremely hot weather on human health, we investigated heat-related deaths in Japan from 1968 through 1994, analyzing the data to determine the distribution of the deaths by age and their correlation to the incidence of hot days in summer. Vital Statistics of Japan, published by the Ministry of Health and Welfare of Japan, was the source of the heat-related mortality data employed in this study. Meteorological data were obtained from the District Meteorological Observatories in Tokyo and Osaka, the two largest cities in Japan. Heat-related deaths were most prone to occur on days with a peak daily temperature above 38 degrees C, and the incidence of these deaths showed an exponential dependence on the number of hot days. Thus, even a small rise in atmospheric temperature may lead to a considerable increase in heat-related mortality, indicating the importance of combating global warming. Furthermore, half (50.1%) of the above-noted deaths occurred in children (4 years and under) and the elderly (70 years and over) irrespective of gender, indicating the vulnerability of these specific age groups to heat. Since a warmer climate is predicted in the future, the incidence of heat waves will increase, and more comprehensive measures, both medical and social, should be adopted for children of 4 years and younger the elderly to prevent heat-related deaths in these age groups.

Adolescent↗

PubMed1999

The vast majority of gastric T cells are polarized to produce T helper 1 type cytokines upon antigenic stimulation despite the absence of Helicobacter pylori infection.

Helicobacter pylori infection is associated with chronic infiltration by various cell types, including T cells, whose cytokine production may regulate the inflammatory reaction as well as local immune response to the bacterium. We prospectively analyzed the constituents of the cellular infiltrates and the cytokines produced by T cells in antral biopsies obtained from 73 subjects with and without H. pylori infection, before and after eradication therapy, and compared them with a histological grade of gastritis. We found that T cells predominated in cell number, followed by granulocytes/monocytes and plasma cells in both H. pylori-infected and H. pylori-uninfected subjects. Despite the absence of H. pylori infection, more than 70% of gastric CD4-positive T cells obtained from uninfected tissue produced interferon-gamma (IFN-gamma) in the cytosol. Upon receptor cross-linking of a CD3 and a CD28 molecule, T cells in both infected and uninfected tissue continuously secreted a far greater amount of IFN-gamma than those in peripheral blood mononuclear cell controls for a period of cell culture, whereas the increase in interleukin-4 (IL-4) was very small, and no increase in IL-2 secretion was seen. In H. pylori-infected patients, IFN-gamma secretion was correlated with the grade of mononuclear cell infiltration and decreased to an uninfected control level after eradication therapy. We did not see the effect of eradication on IL-4 secretion. Anti-H. pylori antibody of the IgG2 subclass was remarkably increased in H. pylori-infected subjects. These results together suggest that gastric T cells are already differentiated to produce a large amount of IFN-gamma by a mechanism unrelated to H. pylori infection. H. pylori infection appeared to activate T cells to secrete even more IFN-gamma, which may contribute to maintaining a perpetual inflammation in H. pylori-infected stomach.

Adult↗

PubMed1999

Early valve failure after aortic valve-sparing root reconstruction.

Aortic valve-sparing root reconstructive surgery has been widely adopted to improve the patient's quality of life. We experienced a patient who required reoperation for progressive aortic regurgitation 17 months after the initial operation of valve-sparing root reconstruction with the reimplantation method in acute aortic dissection. In this study, we were concerned with valve durability because of the absence of sinuses of Valsalva in the new aortic root and the need for careful follow-up after this procedure.

Aortic Valve↗

PubMed1999

Voltage-shift of the current activation in HERG S4 mutation (R534C) in LQT2.

OBJECTIVE: Recently, a novel missense mutation (R534C) in the S4 region of human ether-a-go-go-related gene (HERG) was identified in one Japanese LQT2 family. The S4 region presumably functions as a voltage sensor. However, it has not yet been addressed whether the S4 region of HERG indeed functions as a voltage sensor, and whether these residues play any role in abnormal channel function in cardiac repolarization. METHODS: We characterized the electrophysiological properties of the R534C mutation using the heterologous expression system in Xenopus oocytes. Whole cell currents were recorded in oocytes injected with wild-type cRNA, R534C cRNA, or a combination of both. RESULTS: Clinical features--QTc intervals of all affected patients with R534C mutation in HERG are prolonged ranging from 460 to 680 ms (averaged QTc interval > 540 ms). One member of this family had experienced sudden cardiac arrest, and other suffered from recurrent palpitation. Electrophysiology--Oocytes injected with R534C cRNA did express functional channels with altered channel gating. Kinetic analyses revealed that the R534C mutation shifted the voltage-dependence of HERG channel activation to a negative direction, accelerated activation and deactivation time course, and reduced steady-state inactivation. Quantitative analyses revealed that this mutation did not cause apparent dominant-negative suppression. Computer simulation--Incorporating the kinetic alterations of R534C, however, did not reproduce prolonged action potential duration (APD). CONCLUSIONS: The data revealed that arginine at position 534 in the S4 region of HERG is indeed involved in voltage-dependence of channel activation as a voltage sensor. Our examination indicated that HERG current suppression in R534C mutation was the least severe among other mutations that have been electrophysiologically examined, while affected patients did show significant QT prolongation. This suggest that another unidentified factor(s) that prolong APD might be present.

Action Potentials↗

PubMed1999

Regulation of phosphatidylinositol 4,5-bisphosphate levels and its roles in cytoskeletal re-organization and malignant transformation.

It is well known that phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) plays important roles not only as a precursor lipid for generating second messengers but also as a regulator of cytoskeletal re-organization. The last step of PtdIns(4,5)P2 synthesis is catalyzed by PtdIns monophosphate(PIP) kinase. So far, three type I PIP kinases(alpha, beta, and gamma), which phosphorylate PtdIns(4) to PtdIns(4,5)P2, and three type II PIP kinases(alpha, beta, gamma), which phosphorylate PtdIns(5)P to PtdIns(4,5)P2 have been found. On the other hand, several inositolpolyphosphate 5-phosphatases which convert PtdIns(4,5)P2 to PtdIns(4) are known. Among them, synaptojanin, which associates with tyrosine kinase receptors through an adaptor protein, Ash/Grb2, in response to growth factors, is capable of hydrolyzing PtdIns(4,5)P2 bound to actin regulatory proteins, resulting in actin filament re-organization downstream of tyrosine kinases.

Animals↗

PubMed1999

Efficacy of Choto-san on vascular dementia and the protective effect of the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death.

Two different multicenter studies on the efficacy of Choto-san on patients with vascular dementia, one a well-controlled but non-double blind (60 patients), the other a double-blind controlled study (139 patients), were performed. In the well-controlled study, Choto-san was superior in global improvement rating, utility rating and improvement of subjective symptoms, psychiatric symptoms and disturbance in daily living activities. In the double-blind study, with more objective criteria than the well-controlled study, Choto-san was also superior in global improvement rating, utility rating and improvement of subjective symptoms, psychiatric symptoms and disturbance in daily living activities. These results suggest that Choto-san is effective in the treatment of vascular dementia. Uncaria sinensis (OLIV.) HAVIL. (US) is the main medicinal plant composing Choto-san. Glutamate-induced cell death of cultured cerebellar granule cells was protected by the application of water extract of US in a dose-dependent manner, and concentrations of 10(-5) to 10(-4) g/ml had a significant effect compared to exposure to glutamate only. Further, the increase of 45Ca2+ influx into cells by glutamate was also blocked by the water extract in a dose-dependent manner. These results suggest that US has a protective effect on glutamate-induced neuronal death in cultured cerebellar granule cells through the inhibition of Ca2+ influx.

Activities of Daily Living↗

PubMed1999

Differential influence of tyrosine residues of the common receptor beta subunit on multiple signals induced by human GM-CSF.

BACKGROUND: GM-CSF induces the proliferation and differentiation of a broad range of hematopoietic cells. Stimulation with this cytokine results in the induction of rapid tyrosine phosphorylation of cellular proteins, including the common beta subunit of its receptor. However, the significance of beta subunit phosphorylation with regard to regulation of signaling molecules and the functions of GM-CSF is less well understood. OBJECTIVE: To investigate the role of cytoplasmic tyrosine residues, we performed mutational analyses of the beta subunit. METHODS: A series of beta subunit mutants with 1, some, or all of 8 cytoplasmic tyrosines converted to phenylalanines were constructed. These beta subunit mutants were expressed in murine BA/F3 cells together with the wild-type human alpha subunit, and their potentials to transmit signals were examined. RESULTS: A mutant beta subunit lacking all cytoplasmic tyrosines (Fall) activated JAK2, but not Shc, SHP-2, the Raf/ERK cascade, signal transducer and activator of transcription 5 (STAT5), or the c-fos promoter, nor did it effectively induce proliferation. Adding back each tyrosine to Fall revealed that (1) Tyr577 was necessary and sufficient for Shc phosphorylation; (2) Tyr577, Tyr612, and Tyr695 were involved in activation of SHP-2, the Raf/ERK cascade, and c-fos transcription; and (3) all tyrosines, but particularly Tyr612, Tyr695, Tyr750, and Tyr806, facilitated STAT5 activation. Impaired cell growth was also partly restored by any of the tyrosines. Interestingly, the Fall mutant was still capable of suppressing apoptosis and maintaining cell viability. CONCLUSION: These results provide evidence that beta subunit tyrosines possess distinct, yet overlapping, roles in the activation of multiple signaling pathways induced by GM-CSF. In addition, GM-CSF may activate both beta subunit tyrosine-dependent and -independent pathways, with the latter being sufficient to transmit survival signals.

Animals↗

PubMed1999

Effect of dentin primers containing N-methylolacrylamide or N-methylolmethacrylamide on dentin pretreatment.

The effect of experimental dentin primers containing N-methylolacrylamide (MEAA) or N-methylolmethacrylamide (MEMA) on the bonding of three commercial light-cured resin composite systems [Restorative Z 100 (Scotchbond), Palfique Estelite (Macbond) and Photo Clearfil A (Clearfil Photobond)] to etched dentin was investigated. Water solutions of 35% hydroxyethyl methacrylate (HEMA). 50% MEAA or 30% MEMA were used as dentin primers. The dentin etched with 10% phosphoric acid solution was pretreated with dentin primers for 30 s. The resin composite systems were applied in a Teflon tube positioned onto pretreated dentin surfaces. After water immersion for 1 day, the shear bond strengths were measured. The thicknesses of hybrid layers at dentin-resin interfaces treated with 6 mol/l HCl and 1% NaOCl were measured by scanning electron microscopy. The dentin primer pretreatment increased the bond strengths of all resin composite systems. For Macbond and Clearfil Photobond, the bond strengths (14.2-26.5 MPa) with MEAA and MEMA were higher than those (10.5 and 17.8 MPa) with HEMA. All hybrid layer thicknesses were 1-1.5 microns after HCl immersion. The hybrid layers after NaOCl immersion become narrower. The main fracture pattern of specimens exhibiting high bond strengths (more than 14.2 MPa) was dentin cohesive fracture after bond test. For Macbond and Clearfil Photobond, the layers of specimens pretreated with MEAA and MEMA were clearly thicker than those pretreated with HEMA after NaOCl immersion. MEAA and MEMA solutions were more effective in improving the bond strength of Macbond and Clearfil Photobond to etched dentin than was HEMA. Macbond and Clearfil Photobond created good hybrid dentin layers which could resist NaOCl-attack when MEAA and MEMA solutions were used as dentin primers.

Acrylamides↗

PubMed1999

Serial electroencephalographic findings in patients with MELAS.

To clarify the electroencephalographic characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), the medical records and electroencephalograms of six patients with MELAS and two of their relatives with MELA (mitochondrial myopathy, encephalopathy, and lactic acidosis, without strokelike episodes) were retrospectively reviewed. All have a point mutation in the mitochondrial DNA at nucleotide position 3243. The electroencephalograms (n = 79) were divided into four groups according to the time relation to the strokelike episode: (1) before the first strokelike episode, (2) within 5 days after the strokelike episode (acute stage), (3) between 6 days and 1 month after the strokelike episode (subacute stage), and (4) more than 1 month after the strokelike episode (chronic stage). In the acute stage, 10 of the 11 electroencephalograms (9 strokelike episodes in four patients) revealed focal high-voltage delta waves with polyspikes (FHDPS), which were recognized as ictal electroencephalogram. Ictal events during FHDPS included focal clonic or myoclonic seizure and migrainous headache. In the subacute and chronic stages, focal spikes or sharp waves and 14- and 6-Hz positive bursts were frequently recorded. The authors' results suggest that FHDPSs present a reliable and accurate indicator of a strokelike episode in patients with MELAS.

Adolescent↗

PubMed1999

Argatroban as a potential anticoagulant in cardiopulmonary bypass-studies in a dog model.

Argatroban is a selective thrombin inhibitor synthesized in Japan. Argatroban, which has a high affinity for thrombin, and markedly inhibits thrombin-induced reactions, has been used in patients with artherosclerosis obliterans. The efficiency of argatroban, instead of heparin, as an anticoagulant in dog models of cardiopulmonary bypass was explored. In the first study, argatroban was administered as a bolus plus infusion for 1 h during cardiopulmonary bypass at doses of 1.0 mg + 10 microg/kg per min, 2.0 mg + 10 microg/kg per min and 3.0 mg + 10 microg/kg per min (n = 2 per group). Activated clotting time and arterial gas analyses were performed beforehand and 10 min thereafter. In the second study, there were four groups. In the first group (n = 5), no coated extracorporeal circuit was used and heparin (2 mg/kg) was used as an anticoagulant. In the second group (n = 5), a coated extracorporeal circuit was used and heparin was used (2 mg/kg) as an anticoagulant. In the third group (n = 3), no coated extracorporeal circuit was used and argatroban (2.0 mg + 10 microg/kg per min) was used as an anticoagulant. In the fourth group (n = 5), a coated extracorporeal circuit was used and argatroban was used (2.0 mg + 10 microg/kg per min) as an anticoagulant. All animals were perfused for 120 min at 40 ml/kg per minute. Platelet count, activated clotting time, thrombin-antithrombin III complex, antithrombin III, fibrinogen, fibrinogen degradation products and C3a were measured to evaluate platelet, coagulofibrinolytic and the complement system. Activated clotting time values and the effect of argatroban during cardiopulmonary bypass indicated a dose-dependent response. The next highest dosing group (2.0 mg + 10 microg/kg per minute) had activated clotting time values of 250-300 seconds during cardiopulmonary bypass, and fell after reaching near-normal levels within 60 minutes. No clots were noted in the extracorporeal circuit. The argatroban group showed lower levels in their coagulofibrinolytic system compared with the heparin group. The platelet count remained at a high level in the argatroban group. It is concluded that the combination of heparinized cardiopulmonary bypass circuits, and the use of argatroban as an anticoagulant, is safe and reduces the activation of coagulation and fibrinolytic systems and preserves platelet count.

Animals↗

PubMed1999

Lipase-catalyzed direct and regioselective acylation of flavonoid glucoside for mechanistic investigation of stable plant pigments.

One-step and regioselective acylation of flavonoid glucosides was achieved by lipase-catalyzed transesterification in dry organic media. For example, isoquercitrin (quercetin 3-O-glucoside), one of the flavonol monoglucosides, was converted efficiently to the corresponding aromatic acid ester (isoquercitrin 6''-O-cinnamate) by a lipase with vinyl cinnamate as an acyl donor. The method described, which is the first allowing the direct synthesis of aromatic acid esters of flavonoid glucosides, can be applied to the acylation of other glucosides, including naringin, rutin, callistephin, and chrysanthemin.

Journal Article↗

PubMed1999

Experimental metastasis is suppressed in MMP-9-deficient mice.

Matrix metalloproteinases (MMPs) are thought to play a key role in tumor invasion and metastasis. The role of MMP-9 (gelatinase B) in tumor metastasis was examined in MMP-9-deficient mice produced by gene targeting using embryonic stem cells. MMP-9-deficient mice develop normally and are fertile. In these mice, the number of metastatic colonies of B16-BL6 melanoma cells or Lewis lung carcinoma cells that were implanted intravenously fell by 45% for B16-BL6 melanoma and 59% for Lewis lung carcinoma (p = 0.03 and p = 0.0043, respectively). Gelatin zymography showed that both tumor cell lines did not secrete MMP-9 by themselves but the host cells surrounding the tumor cells secrete MMP-9 in vivo. These results indicated that host-derived MMP-9 plays an important role in the process of tumor metastasis.

Animals↗

PubMed1999

Hepatocyte growth factor promotes migration of human hepatocellular carcinoma via phosphatidylinositol 3-kinase.

Hepatocyte growth factor (HGF) is known to be a potent mitogen and motogen for epithelial cells. Hepatocellular carcinoma (HCC) often metastasizes, and the c-Met/HGF receptor is highly expressed by HCC cells. The aim of this study was to investigate the signaling pathways associated with the motogenic effect of HGF on HCC cells via c-Met. HCC cell lines (Hep3B, HepG2, PLC, and Huh-7) and HCC cells harvested from patients were used for the Boyden chamber assay of chemotactic activity as well as for immunoprecipitation and immunoblotting studies. HGF stimulated the motility of Hep3B, HepG2, and Huh-7 cells in a dose-dependent manner in association with tyrosine phosphorylation of c-Met and activation of phosphatidylinositol 3-kinase (PI3-K). A tyrosine kinase inhibitor (genistein) and a PI3-K inhibitor (wortmannin) prevented the migration of HCC cells. However, migration was not prevented by calphostin C, an inhibitor of protein kinase C (PKC), which is a downstream target of phospholipase Cgamma (PLCgamma). HGF also stimulated the migration of HCC cells obtained from three patients, while wortmannin prevented the migration of these cells. These results indicate that HGF stimulates the migration of HCC cells through the tyrosine phosphorylation of c-Met via activation of PI3-K.

Androstadienes↗

PubMed1999

Acetylcholine-induced membrane potential changes in endothelial cells of rabbit aortic valve.

1. Using a microelectrode technique, acetylcholine (ACh)-induced membrane potential changes were characterized using various types of inhibitors of K+ and Cl- channels in rabbit aortic valve endothelial cells (RAVEC). 2. ACh produced transient then sustained membrane hyperpolarizations. Withdrawal of ACh evoked a transient depolarization. 3. High K+ blocked and low K+ potentiated the two ACh-induced hyperpolarizations. Charybdotoxin (ChTX) attenuated the ACh-induced transient and sustained hyperpolarizations; apamin inhibited only the sustained hyperpolarization. In the combined presence of ChTX and apamin, ACh produced a depolarization. 4. In Ca2+-free solution or in the presence of Co2+ or Ni2+, ACh produced a transient hyperpolarization followed by a depolarization. In BAPTA-AM-treated cells, ACh produced only a depolarization. 5. A low concentration of A23187 attenuated the ACh-induced transient, but not the sustained, hyperpolarization. In the presence of cyclopiazonic acid, the hyperpolarization induced by ACh was maintained after ACh removal; this maintained hyperpolarization was blocked by Co2+. 6. Both NPPB and hypertonic solution inhibited the membrane depolarization seen after ACh washout. Bumetanide also attenuated this depolarization. 7. It is concluded that in RAVEC, ACh produces a two-component hyperpolarization followed by a depolarization. It is suggested that ACh-induced Ca2+ release from the storage sites causes a transient hyperpolarization due to activation of ChTX-sensitive K+ channels and that ACh-activated Ca2+ influx causes a sustained hyperpolarization by activating both ChTX- and apamin-sensitive K+ channels. Both volume-sensitive Cl- channels and the Na+-K+-Cl- cotransporter probably contribute to the ACh-induced depolarization.

Acetylcholine↗

PubMed1999

Effect of contamination and etching on enamel bond strength of new light-cured glass ionomer cements.

The effect of water and saliva contamination on the bond strength of metal orthodontic brackets cemented to etched (10% polyacrylic acid) and unetched human premolar enamel was investigated. Two bonding agents were used: one commercially available product (LC) and one experimental (EX) light-cured glass ionomer. Shear bond strength was measured after aging for 5 minutes, 15 minutes, and 24 hours. The results were compared by ANOVA and Scheffe's tests at p = 0.05. For LC, the bond strength of brackets bonded to etched enamel, with and without contamination, was statistically higher than that of brackets bonded to unetched enamel for all aging times. An exception was the bond strength to unetched enamel with saliva contamination after 24 hours; for EX, this value was statistically higher than that measured on unetched enamel with water contamination. Contamination by saliva did not reduce bond strength to unetched enamel. For both etched and unetched enamel, there was no significant difference between LC and EX after 24 hours for all contamination conditions.

Acid Etching, Dental↗

PubMed1999

A time kinetic study of the effect of aminobisphosphonate on murine haemopoiesis.

We previously showed that aminobisphosphonates (aminoBPs), potent inhibitors of bone resorption, increased the number of osteoclasts and granulocytes, and enhanced the cell size of osteoclasts in vivo, indicating that aminoBPs have a profound effect on murine haemopoiesis. The possible effect of an aminoBP (4-amino-1-hydroxybutylidene-1,1-bisphosphonate; AHBuBP) on murine haemopoiesis in vivo was examined in more detail. Macroscopically, AHBuBP induced the whitened bone marrow (BM) and splenomegaly. Flow cytometric analysis indicated that in BM, AHBuBP reduced the number of mature monocyte-macrophage lineage cells and erythroid cells 1 and 2 d after treatment, respectively, whereas it enhanced granulopoiesis on day 4. In the spleen, both erythropoiesis and granulopoiesis were significantly increased. BM haemopoietic progenitors of granulocyte lineage and of monocyte-macrophage lineage (CFU-G, CFU-M and CFU-GM) were well maintained by the injection of AHBuBP, and even a small increment in these progenitors was observed 2-4 d after treatment. Immunohistochemical examination of BM demonstrated that residential macrophages of erythroblastic islands disappeared. Increased numbers of osteoclasts, as well as enlarged cell size, was confirmed up to 7 d after the treatment, implicating that the inhibition of bone resorption was not due to the reduced generation of osteoclasts by AHBuBP. These results suggest (1) that AHBuBP treatment in vivo rapidly deleted mature residential macrophages from BM, (2) that mature macrophages once deleted did not reappear even when CFU-M and CFU-GM increased in number and the number of Mac-1+/Gr-1- cells recovered to normal, (3) that BM erythropoiesis was significantly decreased due to the lack of erythroblastic islands, and (4) that compensatory erythropoiesis was evoked in the spleen to induce splenomegaly.

Animals↗