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T Ito

Publications and source records attributed to T Ito.

At least 451 records · Page 25Linked to original sources

Recognition of N-glycolylneuraminic acid linked to galactose by the alpha2,3 linkage is associated with intestinal replication of influenza A virus in ducks.

The hemagglutinin (HA) of H3 human influenza viruses does not support viral replication in duck intestine despite its avian origin. A Leu-to-Gln mutation at position 226 and a Ser-to-Gly mutation at position 228 in the HA of human A/Udorn/307/72 (H3N2) permit a reassortant virus [human Udorn HA, with all other genes from A/mallard/New York/6750/78 (H2N2)] to replicate in ducks. To understand the molecular basis of this change in host range restriction, we investigated the receptor specificity of duck influenza viruses as well as of human-duck virus reassortants. The results indicate that the recognition of a glycoconjugate moiety possessing N-glycolneuramic acid (NeuGc) linked to galactose by the alpha2,3 linkage (NeuGcalpha2,3Gal) is associated with viral replication in duck intestine. Immunofluorescence assays with NeuGcalpha2,3Gal-specific antiserum detected this moiety primarily on the crypt epithelial cells of duck colon. Such recognition, together with biochemical evidence of NeuGc in crypt cells, correlated exactly with the ability of the virus to replicate in duck colon. These results suggest that recognition of the NeuGcalpha2,3-Gal moiety plays an important role in the enterotropism of avian influenza viruses.

Animals↗

Sialic acid species as a determinant of the host range of influenza A viruses.

The distribution of sialic acid (SA) species varies among animal species, but the biological role of this variation is largely unknown. Influenza viruses differ in their ability to recognize SA-galactose (Gal) linkages, depending on the animal hosts from which they are isolated. For example, human viruses preferentially recognize SA linked to Gal by the alpha2,6(SAalpha2,6Gal) linkage, while equine viruses favor SAalpha2,3Gal. However, whether a difference in relative abundance of specific SA species (N-acetylneuraminic acid [NeuAc] and N-glycolylneuraminic acid [NeuGc]) among different animals affects the replicative potential of influenza viruses is uncertain. We therefore examined the requirement for the hemagglutinin (HA) for support of viral replication in horses, using viruses whose HAs differ in receptor specificity. A virus with an HA recognizing NeuAcalpha2,6Gal but not NeuAcalpha2,3Gal or NeuGcalpha2,3Gal failed to replicate in horses, while one with an HA recognizing the NeuGcalpha2,3Gal moiety replicated in horses. Furthermore, biochemical and immunohistochemical analyses and a lectin-binding assay demonstrated the abundance of the NeuGcalpha2,3Gal moiety in epithelial cells of horse trachea, indicating that recognition of this moiety is critical for viral replication in horses. Thus, these results provide evidence of a biological effect of different SA species in different animals.

Animals↗

Rat and guinea pig pancreatic acini possess both VIP(1) and VIP(2) receptors, which mediate enzyme secretion.

Pancreatic acini from most species possess vasoactive intestinal peptide (VIP) receptors. Recently, two subtypes of VIP receptors, VIP(1)-R and VIP(2)-R, were cloned. Which subtype exists on pancreatic acini or mediates secretion is unclear. To address this, we examined pancreatic acini from both rat and guinea pig. VIP(1)-R and VIP(2)-R mRNA were identified in dispersed acini from both species by Northern blot analysis and in rat by Southern blot analysis. With the use of the VIP(2)-R-selective ligand Ro-25-1553 in both species, inhibition of binding of (125)I-labeled VIP to acini showed a biphasic pattern with a high-affinity component (10%) and a second representing 90%. The VIP(1)-R-selective ligand, [Lys(15),Arg(16),Leu(27)]VIP-(1-7)-GRF-(8-27), gave a monophasic pattern. Binding of Ro-25-1553 was better fit by a two-site model. In both rat and guinea pig acini, the dose-response curve of Ro-25-1553 for stimulation of enzyme secretion was biphasic, with a high-affinity component of 10-15% of the maximal secretion and a low-affinity component accounting for 85-90%. At low concentrations (10 nM) of Ro-25-1553 and [Lys(15),Arg(16), Leu(27)]VIP-(1-7)-GRF(8-27), which only occupy VIP receptors, a 4-fold and a 56-fold increase in cAMP occurred, respectively. These results show that both VIP(1)-R and VIP(2)-R subtypes exist on pancreatic acini of rat and guinea pig, their activation stimulates enzyme secretion by a cAMP-mediated mechanism, and the effects of VIP are mediated 90% by activation of VIP(1)-R and 10% by VIP(2)-R. Because VIP has a high affinity for both VIP-R subtypes, its effect on pancreatic acini is mediated by two receptor subtypes, which will need to be considered in future studies of the action of VIP in the pancreas.

Animals↗

Vagus nerve is involved in lack of blood reflow into sinusoids after rat hepatic ischemia.

Although recovery of microcirculation is an important determinant for ischemia-reperfusion injury, little information is available about hepatic blood flow after ischemia. To examine regulatory mechanisms of postischemic hepatic microcirculation, we studied the sinusoidal blood flow after portal triad clamping of rat livers for 5, 15, or 30 min. Hepatic tissue blood flow and erythrocyte blood flow in sinusoids were measured using a laser-Doppler flowmeter and an intravital microspectroscope, respectively. There was a time of no blood flow (lag time) in sinusoids after declamping, dependent on the ischemic time. Cholinergic blockade agents eliminated the lag time, whereas nerve stimulation at the hiatus esophagus or on the hepatoduodenal ligament during reperfusion prolonged it. Chemical denervation with 10% phenol or surgical denervation on the hepatoduodenal ligament eliminated the lag time. The prolongation of lag time by nerve stimulation was completely abrogated by truncal vagotomy. These results suggest that the cholinergic vagus nerve is involved in causing the lag time of sinusoidal blood flow in hepatic ischemia-reperfusion.

Animals↗

Functional expression of novel peptide transporter in renal basolateral membranes.

We examined the peptide transport activity in renal basolateral membranes. [(14)C]glycylsarcosine (Gly-Sar) uptake in rat renal cortical slices was saturable and inhibited by excess dipeptide and aminocephalosporin cefadroxil. When several renal cell lines were screened for the basolateral peptide transport activity, Madin-Darby canine kidney (MDCK) cells were demonstrated to have the greatest transport activity. [(14)C]Gly-Sar uptake across the basolateral membranes of MDCK cells was inhibited by di- and tripeptide and decreased with decreases in extracellular pH from 7.4 to 5.0. The Michaelis-Menten constant value of [(14)C]Gly-Sar uptake across the basolateral membranes of MDCK cells was 71 microM. The basolateral peptide transporter in MDCK cells showed several different [(14)C]Gly-Sar transport characteristics in growth dependence, pH profile, substrate affinity, and sensitivities to chemical modifiers from those of the apical H(+)-peptide cotransporter of MDCK cells. The findings of the present investigation indicated that the peptide transporter was expressed in the renal basolateral membranes. In addition, from the functional characteristics, the renal basolateral peptide transporter was suggested to be distinguishable from known peptide transporters, i.e., H(+)-peptide cotransporters (PEPT1 and PEPT2) and the intestinal basolateral peptide transporter.

4-Chloromercuribenzenesulfonate↗

p38 MAP kinase is required for vasopressin-stimulated HSP27 induction in aortic smooth muscle cells.

We previously showed that arginine vasopressin (AVP) stimulates heat shock protein 27 (HSP27) induction through protein kinase C activation in aortic smooth muscle A10 cells. In the present study, we examined whether the mitogen-activated protein (MAP) kinase superfamily is involved in the AVP-stimulated HSP27 induction in A10 cells. AVP stimulated the phosphorylation of p42/p44 MAP kinase and p38 MAP kinase. On the contrary, AVP had little effect on SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase) phosphorylation. The HSP27 accumulation by AVP was not affected by PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase. SB203580 and PD169316, specific inhibitors of p38 MAP kinase, suppressed the AVP-induced accumulation of HSP27. 12-O-tetradecanoylphorbol 13-acetate, an activator of protein kinase C, induced accumulation of HSP27 and was not inhibited by PD98059 but was inhibited by SB203580. Calphostin C and ET-18-OCH(3), inhibitors of protein kinase C, reduced the phosphorylation of p38 MAP kinase by AVP. SB203580 and PD169316 suppressed the AVP-increased levels in mRNA for HSP27. Dissociation of the aggregated HSP27 to the dissociated HSP27 was induced by AVP. These results strongly suggest that p38 MAP kinase takes part in the pathway of the AVP-stimulated induction of HSP27 in vascular smooth muscle cells.

Animals↗

Angiotensin II AT(1) blockade normalizes cerebrovascular autoregulation and reduces cerebral ischemia in spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: Angiotensin II, through stimulation of AT(1) receptors, not only controls blood pressure but also modulates cerebrovascular flow. We sought to determine whether selective AT(1) antagonists could be therapeutically advantageous in brain ischemia during chronic hypertension. METHODS: We pretreated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls with the AT(1) antagonist candesartan (CV-11974), 0.5 mg/kg per day, for 3 to 14 days, via subcutaneously implanted osmotic minipumps. We analyzed cerebral blood flow by laser-Doppler flowmetry, cerebral stroke in SHR after occlusion of the middle cerebral artery with reperfusion, and brain AT(1) receptors by quantitative autoradiography. RESULTS: Candesartan treatment normalized blood pressure and the shift toward higher blood pressures at both the upper and lower limits of cerebrovascular autoregulation in SHR. Candesartan pretreatment of SHR for 14 days partially prevented the decrease in blood flow in the marginal zone of ischemia and significantly reduced the volume of total and cortical infarcts after either 1 or 2 hours of middle cerebral artery occlusion with reperfusion, relative to untreated SHR, respectively. This treatment also significantly reduced brain edema after 2 hours of middle cerebral artery occlusion with reperfusion. In SHR, candesartan markedly decreased AT(1) binding in areas inside (nucleus of the solitary tract) and outside (area postrema) the blood-brain barrier and in the middle cerebral artery. CONCLUSIONS: Pretreatment with an AT(1) antagonist protected hypertensive rats from brain ischemia by normalizing the cerebral blood flow response, probably through AT(1) receptor blockade in cerebral vessels and in brain areas controlling cerebrovascular flow during stroke.

Angiotensin II↗

Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium.

To clarify the mechanisms that regulate neuroendocrine differentiation of fetal lung epithelia, we have studied the expression of the mammalian homologs of achaete-scute complex (Mash1) (Ascl1 - Mouse Genome Informatics); hairy and enhancer of split1 (Hes1); and the expression of Notch/Notch-ligand system in the fetal and adult mouse lungs, and in the lungs of Mash1- or Hes1-deficient mice. Immunohistochemical studies revealed that Mash1-positive cells seemed to belong to pulmonary neuroendocrine cells (PNEC) and their precursors. In mice deficient for Mash1, no PNEC were detected. Hes1-positive cells belong to non-neuroendocrine cells. In the mice deficient in Hes1, in which Mash1 mRNA was upregulated, PNEC appeared precociously, and the number of PNEC was markedly increased. NeuroD (Neurod1 - Mouse Genome Informatics) expression in the lung was detected in the adult, and was enhanced in the fetal lungs of Hes1-null mice. Expression of Notch1, Notch2, Notch3 and Notch4 mRNAs in the mouse lung increased with age, and Notch1 mRNA was expressed in a Hes1-dependent manner. Notch1, Notch2 and Notch3 were immunohistochemically detected in non-neuroendocrine cells. Moreover, analyses of the lungs from the gene-targeted mice suggested that expression of Delta-like 1 (Dll1 - Mouse Genome Informatics) mRNA depends on Mash1. Thus, the neuroendocrine differentiation depends on basic helix-loop-helix factors, and Notch/Notch-ligand pathways may be involved in determining the cell differentiation fate in fetal airway epithelium.

Aging↗

Stilbenoids isolated from stem bark of Shorea hemsleyana.

Two new stilbene glucosides [(+)-alpha-viniferin 13b-O-beta-glucopyranoside and resveratrol 12-C-beta-glucopyranoside] and two new resveratrol oligomers, hemsleyanols A and B, were isolated from the bark of Shorea hemsleyana along with four known resveratrol oligomers. The structures of the isolates, including the relative configurations, were established by spectroscopic data involving long-range coupling and nuclear Overhauser effect experiments.

Magnetic Resonance Spectroscopy↗

The controlled release of a drug from biodegradable chitosan gel beads.

Chitosan (CS) forms a gel in solutions with a pH above 12, and the gelation occurs at pH of about 9 in 10% amino acid solutions. In this paper, we investigated the enzymatic degradation and the drug release profile of this novel CS gel beads. The degradability of the CS gel beads was affected by the CS properties, e.g. the degree of deacetylation. The release of prednisolone (PS), as a model drug, from the CS gel beads was sustained significantly compared with the gel prepared with NaOH only. However, the release was not able to be sustained by the increment of NaOH concentration in the solution employed for the preparation of CS gel beads. We also investigated the control of drug release from CS gel beads by application of a complex formed between chondroitin sulfate (Cho) and CS. The release of PS from the CS gel beads treated with Cho was prolonged, and the release pattern was not affected by the treatment time. The time to 50% drug release was about 5 min with PS powder, about 200 min in CS gel beads with 10% glycine (Gly) (pH 9.0), and about 330 min in the CS gel beads with 10% Gly (pH 9.0) treated with Cho. Thus CS gel beads appear promising as a vehicle for sustained drug delivery, and the degradation of CS gel beads may be controlled by the degree of deacetylation of CS.

Chitin↗

A case of primary cardiac B cell lymphoma associated with ventricular tachycardia, successfully treated with systemic chemotherapy and radiotherapy: a long-term survival case.

We experienced a long-term survival case of primary cardiac lymphoma (PCL) demonstrating ventricular tachycardia (VT) as an initial sign, which was related to localized myocardial damage by lymphoma cells. A 70-year-old woman with sustained VT was admitted to the Kofu Municipal Hospital. VT ceased with the administration of disopyramide intravenously. The origin of the VT was the free wall of the right ventricular outflow tract (RVOT) as observed by electrocardiography on admission. A solitary mass in the free wall of the RVOT was found by echocardiography, chest computed tomographic scanning and magnetic resonance imaging. There was no evidence of extracardiac involvement. The patient was histologically diagnosed as PCL by endomyocardial biopsy. Chemotherapy started immediately after the diagnosis and the mass showed a marked reduction in size. After 8 cycles of chemotherapy, radiotherapy was performed. Pericardial thickness in the free wall of the RVOT developed without severe side effects. Complete remission has been maintained for 30 months after the initial diagnosis, and no recurrence and arrhythmias have been detected during the follow-up period. It was demonstrated that rapid diagnosis and chemotherapy followed by radiotherapy for PCL achieved better survival.

Aged↗

Prognostic value of left atrial appendage function in patients with dilated cardiomyopathy.

The purpose of the present study was to determine whether parameters of left atrial appendage (LAA) function, assessed by transesophageal echocardiography (TEE), could predict the clinical outcome in patients with dilated cardiomyopathy (DCM). Fifty-five patients (20 had ischemic cardiomyopathy; mean age, 56+/-14 years) who underwent TEE to evaluate LAA function from 1992 to 1996 were studied. After a mean follow-up period of 34+/-13 months, 16 patients died; the cause was cardiac in 14 and noncardiac in 2. Patients who died of cardiac cause had a lower LAA emptying velocity than survivors (38+/-18 vs 54+/-18 cm/s, p=0.01). There were, however, no significant differences between survivors and nonsurvivors with regard to the maximal LAA area (4.3+/-1.3 vs 4.5+/-0.9 cm2, p=0.55), minimal LAA area (2.4+/-1.1 vs 2.9+1.1 cm2, p=0.13), and LAA ejection fraction (46+/-16 vs 36+/-18%, p=0.05). On the Cox proportional hazards model analysis, LAA emptying velocity <50 cm/s (chi-square 5.9, p=0.02), LAA ejection fraction <43% (chi-square 5.6, p=0.02), female gender (chi-square 5.2, p=0.02), pulmonary artery wedge pressure > or =14 mmHg (chi-square 4.8, p=0.03), E/A ratio > or =1.3 (chi-square 4.6, p=0.03), deceleration time <148 ms (chi-square 4.6, p=0.03), and cardiothoracic ratio > or =54% (chi-square 4.3, p=0.04) were significantly related to cardiac death. The stepwise multivariate analysis revealed that LAA emptying velocity (chi-square 6.1, p=0.01) and gender (chi-square 5.4, p=0.02) were the independent predictors for outcome. In conclusion, the parameters of LAA function may be useful predictors of the clinical outcome in patients with DCM.

Adult↗

Effects of topically applied capsaicin cream on neurogenic inflammation and thermal sensitivity in rats.

The effects of capsaicin cream on neurogenic inflammation and thermal nociceptive threshold were investigated in rats. Firstly, for topical application of capsaicin cream to hind paw, we shaped boots from dental cement to prevent the animals from licking off the drug. Capsaicin cream (1%) led to significant increases in the amounts of Evans blue and substance P (SP) released into the perfusate, and the former response was significantly suppressed by pretreatment with RP67580, an NK1-receptor antagonist, but not by treatment with an NK2-receptor antagonist. Subsequent electrical stimulation of the sciatic nerve resulted in a significant reduction in Evans blue and SP extravasation 24 h after topical application of capsaicin cream. On the other hand, when capsaicin cream was repeatedly applied to both hind paws once a day, withdrawal latency for noxious heat stimulation decreased after 24 h, and this thermal hyperalgesia was reversed 3 days later. These results suggest that capsaicin cream initially affects neurogenic inflammation mechanisms and then blocks the pain transmission mechanism.

Administration, Topical↗

Functions of semaphorins in axon guidance and neuronal regeneration.

The semaphorin family comprises secreted and transmembrane signaling proteins that function in the nervous, immune, respiratory and cardiovascular systems. Sema3A, a secreted type of semaphorin, is now recognized as the most potent repulsive molecule inhibiting or repelling neurite outgrowth. The biological actions of Sema3A are mediated via neuropilin (Npn)-1, a receptor or one of the components of a receptor complex for Sema3A. Although the molecular mechanisms of Sema3A-Npn-1 signaling are largely unknown, a pertussis toxin-sensitive trimeric G protein(s), Rac-1, collapsin response mediator protein (CRMP), cyclic nucleotides and tyrosine kinase(s) have been implicated as essential and/or modulatory components of these processes. As repulsive molecules could be impediments to axon outgrowth, determining how these repulsive molecules exert their actions has the potential of uncovering new therapeutic approaches to injury and/or degeneration of neuronal tissues.

Animals↗

C-reactive protein (CRP) measurement in canine serum following experimentally-induced acute gastric mucosal injury.

To establish the diagnostic significance of canine C-reactive protein (CRP) in gastrointestinal disorders, the serum canine CRP concentration was measured in dogs with experimentally-induced acute gastric mucosal injury. Gastric injury was induced in one male and one female beagle by a single dose oral administration of acetylsalicylic acid (200 mg/kg body weight) or indomethacin (60 mg/kg body weight), or sodium chloride (1,000 mg/kg body weight). CRP was measured prior to dose, and 1, 3, 7, and 14 days after the administration of the drugs, together with the total leucocyte counts and serum iron. Changes in the serum CRP in dogs with gastric injury were similar for the three test compounds, and reflected by the endoscopic findings. CRP values increased from 87 to 390 mg/l within 1 to 3 days after the compound administration but returned nearly to the predose levels within 14 days. Endoscopy revealed haemorrhagic erosion of the gastric mucosa in all dogs one day after dosing, with no evidence of the erosions observed after 7 days in many of the dogs. Changes of the total leucocyte and serum iron also occurred following gastric injury, but these changes were not as marked as those observed for CRP. The results of this study suggest that serum CRP level may be a useful indicator of a gastrointestinal mucosal injury in dogs.

Animals↗

Purification and characterization of biliverdin-binding protein from larval hemolymph of the swallowtail butterfly, Papilio xuthus L.

The biliverdin-binding protein from the larval hemolymph of the swallowtail butterfly, Papilio xuthus L., was purified and characterized. The crude biliverdin-binding protein, obtained by ammonium sulfate fractionation, was purified in two steps, the first one by gel filtration chromatography and the second one by ion-exchange chromatography. The molecular mass of the purified protein was analyzed by SDS-polyacrylamide gel electrophoresis and estimated to be 21 kDa. The Namino terminal sequence of P. xuthus biliverdin-binding protein analyzed up to the 19th residue showed that 42% of the amino acid sequence are sequence similarity to the bilin-binding protein from Pieris brassicae. These results suggest that the P. xuthus biliverdin-binding protein belongs to the insecticyanin-type.

Amino Acid Sequence↗

Plasma levels and redox status of ascorbic acid and levels of lipid peroxidation products in active and passive smokers.

Both active and passive smoking are regarded as risk factors for various diseases. To clarify the effects of active and passive smoking on plasma vitamin C levels and lipid peroxidation status, we examined the plasma levels of ascorbic acid (AA), its redox status [ratio of dehydroascorbate (DHAA) to total AA], the levels of thiobarbiturate reactive substance (TBARS), and the levels of lipid peroxides (LPO) in smokers, nonsmokers, and nonsmokers regularly exposed to environmental cigarette smoke (passive smokers). The study population consisted of 149 healthy males: 75 active smokers (consumption of > 15 cigarettes/day for more than 5 years), 36 passive smokers (more than 10 hr/week exposure to environmental cigarette smoke), and 38 nonsmokers (no cigarette smoke exposure). There were no significant differences in plasma TBARS and LPO levels among the three groups. Plasma levels of AA, the reduced form of vitamin C, were significantly lower in active smokers than in the combined nonsmoking groups (7.2 +/- 3.5 and 8.4 +/- 3.4 microg/mL, respectively; p < 0.05). Although no significant differences were found in plasma DHAA levels among the three groups, the ratios of DHAA to total AA were significantly higher in active and passive smokers than nonexposed nonsmokers (11.2, 10.3, and 7.1%, respectively; p < 0.05). These results indicate that passive smoking, as well as direct inhalation of cigarette smoke, affects the redox status of plasma AA. In passive smokers, the altered redox status of plasma AA suggests an oxidative stress.

Adult↗