Search PubMed⌕ Search

Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 325 records · Page 18Linked to original sources

Prolongation of liver allograft survival after interleukin-10 gene transduction 24-48 hours before donation.

BACKGROUND: Interleukin- (IL) 10 may be a potent regulator for controlling of allograft rejection. A single administration of IL-10 is not effective for controlling graft rejection. Gene transfer is an attractive vehicle for prolonging the expression of short-lived proteins. METHODS: Donor or recipient livers were transduced with 1 x 10(10) p.f.u. of replication-deficient adenovirus vectors harboring human IL-10 cDNA (AdCMVhIL-10) via the ileocecal vein before or after rat orthotopic liver transplantation. RESULTS: DA allografts given AdCMVhIL-10 24-48 hr before donation survived for more than 56 days in Lewis recipients, although DA allografts given the adenovirus vector 7 days or 6 hr before, and 3 days after transplantation were rejected within 30 days in recipients. Serum levels of human IL-10 in gene-transferred rats were maximum from day 2 to 7. The serum level of human IL-10 then decreased gradually, and human IL-10 was not detected by ELISA 30 days after gene-transduction. In gene-transduced long-term surviving liver allografts, IL-10 was expressed, and the expression of IL-4 was also up-regulated on posttransplant day 3, despite the expression of Th1 cytokines (IL-2 and interferon-gamma), although in rejected liver allografts, IL-2 and interferon-gamma were expressed without expression of IL-4 and IL-10. CONCLUSIONS: The prolongation of survival of IL-10 cDNA transferred liver allografts might be due to inhibition of the early phase of alloimmune-response by over expression of IL-10, despite the expression of IL-2 and interferon-gamma.

Animals↗

Parathyroid hormone-related peptide inhibits the expression of bone morphogenetic protein-4 mRNA through a cyclic AMP/protein kinase A pathway in mouse clonal chondrogenic EC cells, ATDC5.

The bone morphogenetic proteins (BMPs) play crucial roles in chondrogenic differentiation. Little is known, however, regarding the regulation of BMP gene expression. Here we examined the effect of parathyroid hormone-related peptide (PTHrP) (1-141), a full-length form of PTHrP molecules, on the expression of BMP-4 mRNA in clonal mouse chondrogenic EC cells, ATDC5. In differentiated ATDC5 cells, the expression of BMP-4 mRNA was inhibited by PTHrP (1-141), which stimulated cAMP accumulation and protein kinase A (PKA) activity in these cells. Dibutyryl cAMP, a permeable analog of cAMP, mimicked and H-89, a selective PKA inhibitor, blocked this effect of PTHrP (1-141). Moreover, actinomycin D attenuated the inhibition of BMP-4 mRNA expression by PTHrP (1-141). These results indicate that PTHrP (1-141) transcriptionally inhibits the expression of BMP-4 mRNA through a cAMP/PKA pathway in ATDC5 cells.

Animals↗

Xylem-specific expression of wound-inducible rice peroxidase genes in transgenic plants.

A peroxidase gene, poxA, was isolated from a rice (Oryza sativa L.) genomic library. The gene consists of four exons whose combined sequences were identical to that of the prxRPA mRNA whose levels were dramatically stimulated by wounding as well as by treatment of rice shoots with ethephon or UV irradiation [H. Ito, F. Kimizuka, A. Ohbayashi, H. Matsui, M. Honma, A. Shinmyo, Y. Ohashi, A.B. Caplan, R.L. Rodriguez, Molecular cloning and characterization of two complementary DNAs encoding putative peroxidases from rice (Oryza sativa L.) shoots, Plant Cell Rep. 13 (1994) 361-366]. The temporal and spatial expression properties of the poxA gene promoter as well as that from a second related peroxidase gene, poxN, were analyzed in transgenic tobacco and rice plants using the uidA gene as a reporter. In transgenic tobacco, UV- and wound-responsive cis-elements were located within 144 bp from the translational start codon of the poxA gene. The poxN promoter, however, was inactive in the heterologous host as no significant GUS activity was evident. On the other hand, chimeric uidA genes containing 2.2 kb of the poxA promoter or 1.4 kb of poxN promoter were active in transgenic rice plants. Both peroxidase promoters directed GUS activities in a spatial and tissue specific manner coincident with the expression patterns exhibited by their mRNAs. Histochemical analysis of transgenic rice plants showed that both peroxidase genes are expressed in the vascular bundles of the shoot apex and lamina joint, and in xylem-parenchyma cells of the leaf blade and sheath.

Journal Article↗

Thalamic abnormalities in patients with schizophrenia revealed by proton magnetic resonance spectroscopy.

Recent investigations suggest that thalamic abnormalities may underlie symptom formation in schizophrenia. We previously demonstrated reduced concentrations of N-acetylaspartate (NAA) in tissue from the thalamus of schizophrenic patients using in vitro proton magnetic resonance spectroscopy (1H-MRS). In the present study, in vivo 1H-MR spectra of the left thalamus and frontal lobe were investigated in 20 patients with schizophrenia and 16 age-matched control subjects to replicate our previous postmortem findings and support the hypothesis of thalamic abnormality in schizophrenia. Schizophrenic patients showed significantly lower NAA/total creatine (Cr) and choline-containing compounds (Cho)/Cr ratios in the thalamus than control subjects, while no significant difference was found in the frontal lobe. There was no significant correlation in the schizophrenic patients between the NAA/Cr or Cho/Cr ratio and other clinical data including clinical symptoms or neuroleptic dosage. These findings may further support other studies suggesting decreased thalamic volume or neuronal number and/or thalamic dysfunction, and reduction in size of white matter tracts adjacent to the thalamus in schizophrenia, as well as our previous postmortem MRS study.

Adult↗

The role of 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptors in the regulation of gut motility in the ferret.

The role of 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptors in the regulation of gut motility in the ferret was investigated. The selective 5-HT3 receptor antagonist ramosetron (1 - 10 microg/kg s.c.) prolonged the interval of gastric antral migrating motor complex, but had only slight effect on small intestinal and colonic motility in unfed animals. The selective 5-HT4 receptor antagonist SB 204070 did not affect motility throughout gut in unfed animals. Neither ramosetron nor SB 204070 affected the motility throughout gut in fed animals. In conclusion, neither 5-HT3 nor 5-HT4 receptors tonically regulate ferret gut motility except that 5-HT3 receptors have a key role in the occurrence of migrating motor complex specifically in the stomach. The role of 5-HT3 and 5-HT4 receptor system in the regulation of gut motility in ferrets is similar to that in other mammalian species studied, including humans. This similarity suggests that the ferret is a suitable model animal to study gut motor functions in humans.

Animals↗

IL-6 is required for the development of Th1 cell-mediated murine colitis.

Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis of Crohn's disease. Among those cytokines, strong expression of IL-6 has been repeatedly demonstrated. To examine the role for IL-6 in the pathogenesis of Crohn's disease, we introduced anti-IL-6R mAb to a murine model of colitis. Colitis was induced in C.B-17-scid mice transferred with CD45RBhigh CD4+ T cells from BALB/c mice. Anti-IL-6R mAb or rat IgG was administered weekly after T cell transfer. ICAM-1 and VCAM-1 expression were analyzed by immunohistochemistry. Colonic cytokine expression was determined by RT-PCR. Mice treated with mAb showed normal growth, whereas controls lost weight. The average colitis score was 0.64 for mAb-treated mice and 1.80 for controls. T cell expansion in treated mice was less remarkable than in the controls. Colonic ICAM-1 and VCAM-1 expression were markedly suppressed by mAb. IFN-gamma, TNF-alpha, and IL-1beta mRNA were reduced by the treatment. The results presented here show a crucial role for IL-6 in the pathogenesis of murine colitis and suggest a therapeutic potential of anti-IL-6R mAb for treatment of human Crohn's disease.

Animals↗

Restoration of effectiveness of beta-lactams on methicillin-resistant Staphylococcus aureus by tellimagrandin I from rose red.

We found that extract from petals of Rosa canina L. (rose red) strikingly reduced the minimum inhibitory concentration of beta-lactams in methicillin-resistant Staphylococcus aureus. We isolated two compounds that reduced the minimum inhibitory concentrations of beta-lactams from the extract, tellimagrandin I and rugosin B. Tellimagrandin I was very effective regarding the reduction of the minimum inhibitory concentration, and rugosin B showed some effect. Tellimagrandin I showed a weak bactericidal action when added together with oxacillin. Judging from the fractional inhibitory concentration index, the effect of tellimagrandin I and oxacillin was synergistic. Tellimagrandin I also significantly reduced the minimum inhibitory concentration of tetracycline in some strains of methicillin-resistant Staphylococcus aureus.

Anti-Bacterial Agents↗

Diverse expression profiles of 21 rice peroxidase genes.

Secretory class III plant peroxidases (POXs) catalyze the oxidation of various reductants, and are encoded by a large multigene family. In rice, 42 independent expressed sequence tags for POXs have been identified. By RNA gel blot analysis using specific probes, we show here that 21 rice POX genes are unique in their developmental, organ specific and external stimuli-responsive expression. This would suggest that encoded POX isoenzymes are involved in a broad range of physiological processes in rice plants, individually.

Expressed Sequence Tags↗

In vivo transfer of hepatocyte growth factor gene accelerates proliferation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rats.

To clarify the effect of hepatocyte growth factor (HGF) on proliferation of hepatic oval cells, we transferred HGF gene into liver of the Solt-Farber rat model. Male Fisher 344 rats were infected with a recombinant adenovirus carrying the cDNA for HGF (pAxCAHGF) from tail vein. HGF mRNA showed its peak at 4 days, and diminished thereafter. The total and proliferating cell nuclear antigen-positive hepatic oval cells were significantly elevated in HGF-transferred rats, in which stem cell factor and c-kit mRNA increased at each time point. Our results suggest that in vivo transfer of the HGF gene into liver accelerates proliferation of hepatic oval cells in the Solt-Farber model in rats.

2-Acetylaminofluorene↗

Use of echocardiography for predicting myocardial viability in patients with reperfused anterior wall myocardial infarction.

Dobutamine stress echocardiography (DSE), myocardial contrast echocardiography (MCE), and ultrasonic tissue characterization with integrated backscatter are useful methods for assessing myocardial viability in acute myocardial infarction. In this study, we compared the potential of 3 methods for predicting myocardial viability in 38 patients with reperfused anterior wall acute myocardial infarction. We performed MCE shortly after coronary reperfusion with an intracoronary injection of microbubbles. We recorded 2-dimensional integrated backscatter images at rest and, then, performed low-dose (10 microg/kg/min) DSE 3 days later. In integrated backscatter images, we placed the region of interest in the midwall of the myocardial segment to reconstruct the cyclic variation of myocardial integrated backscatter. The myocardial segment was judged viable when it showed active contraction 3 months later. Among 74 segments analyzed, 34 were judged viable. Presence of contractile response during DSE predicted segmental viability with 91% sensitivity and 78% specificity. Intense and homogenous contrast enhancement with MCE predicted viability with 82% sensitivity and 73% specificity. The presence of synchronous contraction of cyclic variation predicted myocardial viability with 79% sensitivity and 83% specificity. There were no differences in sensitivity and specificity among the 3 methods. Thus, MCE and ultrasonic tissue characterization can predict myocardial viability as accurately as DSE in patients with acute myocardial infarction. The logistics of the methods may determine clinical application.

Angioplasty, Balloon, Coronary↗

Molecular cloning and expression of mouse GD1alpha/GT1aalpha/GQ1balpha synthase (ST6GalNAc VI) gene.

A novel member of the mouse CMP-NeuAc:beta-N-acetylgalactosaminide alpha2,6-sialyltransferase (ST6GalNAc) subfamily, designated ST6GalNAc VI, was identified by BLAST analysis of expressed sequence tags. The sequence of the cDNA clone of ST6GalNAc VI encoded a type II membrane protein with 43 amino acids composing the cytoplasmic domain, 21 amino acids composing the transmembrane region, and 269 amino acids composing the catalytic domain. The predicted amino acid sequence showed homology to the previously cloned ST6GalNAc III, IV, and V, with common amino acid sequences in sialyl motif L and S among these four enzymes. A fusion protein with protein A and extracts from L cells transfected with ST6GalNAc VI in an expression vector showed enzyme activity of alpha2,6-sialyltransferase for GM1b, GT1b, and GD1a but not toward glycoproteins. Thin layer chromatography-immunostaining revealed that the products were GD1alpha, GQ1balpha, and GT1aalpha. Northern blotting revealed that this gene was expressed in a wide range of mouse tissues such as colon, liver, heart, spleen, and brain. It is concluded that this enzyme is a novel sialyltransferase involved in the synthesis of alpha-series gangliosides in the nervous tissues and many other tissues.

Amino Acid Sequence↗

Preoperative treatment with tegafur suppositories enhances apoptosis and reduces the intratumoral microvessel density of human colorectal carcinoma.

BACKGROUND: This study examined the effect of tegafur, a depot of 5-fluorouracil, in human colorectal carcinomas in terms of apoptosis, cell proliferation, and expression of p53 gene and angiogenesis-related molecules. METHODS: A total of 32 patients with colorectal carcinoma were divided into 2 groups; 20 patients received tegafur suppositories (TS) at 1 g/day for 14 days before surgery, and 12 patients did not receive any chemotherapy. Surgically removed specimens were examined immunohistochemically for Ki-67, CD34, p53, p21, Bax, vascular endothelial growth factor (VEGF), and thymidine phosphorylase (dThdPase). Apoptotic tumor cells were visualized by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) procedure. RESULTS: The mean percentage of apoptotic index (AI) was 6.9 +/- 1.2 in the 20 TS-treated tumors and 4.4 +/- 1.0 in the 12 nontreated tumors (P < 0.001). In contrast, the mean percentage of Ki-67 labeling index (KI) became significantly lower in the former group (P < 0.05). The frequency of p21 expression was significantly higher in the TS-treated group than in the nontreated group (P < 0.05), whereas no difference was detected in p53 and Bax expression between the two groups. The mean intratumoral microvessel density was 47.8 +/- 19.8 in the TS-treated tumors and 66.8 +/- 16.5 in the nontreated tumors (P < 0.01). The frequency of dThdPase expression, but not of VEGF expression, became significantly lower with the TS treatment. p53 expression did not correlate with AI, KI, IMV density, or the expression of VEGF, p21, or Bax, except for dThdPase, which was significantly higher in the 18 p53 positive tumors (P < 0.05). CONCLUSIONS: Preoperative TS treatment enhances apoptosis and suppresses angiogenesis of colorectal carcinomas in a p53-independent manner.

Aged↗

Balance of two secretion pathways of nerve growth factor in PC12 cells changes during the progression of their differentiation, with a decrease in constitutive secretion in more differentiated cells.

Proteins are secreted from animal cells by either a constitutive or a regulated pathway. When cDNA of nerve growth factor (NGF) was introduced into PC12 cells, these cells produced and secreted active NGF, where NGF was secreted not only in constitutive but also in activity-dependent regulated way according to the results of pulse-chase and ELISA studies. The regulated secretion was caused by depolarization, cyclic AMP analogue, or beta-adrenergic agonist but not by glutamate or carbachol. Because these transfected cells differentiated into a morphology indistinguishable from that incubated with NGF protein, we next compared the secretion pathways of NGF from PC12 cells at different stages of the differentiation. NGF was secreted in both constitutive and regulated way at 2 and 7 days after the transfection of NGF-cDNA, but the constitutive secretion of NGF from the more differentiated cells of Day 7 was decreased and mature NGF tended to accumulate in the cells. These results indicate that the neurotrophin secretion mechanism is intimately regulated in the course of the differentiation of PC12 cells. Such a change in the protein secretion pathway might have an profound role in the development of neurons.

Animals↗

Prevention of v-Ha-Ras-dependent apoptosis by PDGF coordinates in phosphorylation of ERK and Akt.

In some v-Ha-ras-transfected cell lines, serum deprivation results in apoptosis. Clarification of the molecular mechanisms by which oncogenic Ras controls susceptibility to apoptosis may assist in the development of effective therapies against human cancer with oncogenic ras gene. In this report, we established a v-Ha-ras-transfected human fibroblast clone, R1. In R1 cells, induction of v-Ha-Ras enhanced susceptibility to cell death under serum-deprived conditions. Ladders of cellular DNA were identified only when oncogenic ras was induced under serum-deprived conditions. Platelet-derived growth factor (PDGF) precluded DNA fragmentation of serum-deprived v-Ha-ras-transformed cells. Under serum-depleted conditions, the amounts of activated ERK and Akt decreased as compared with those under serum-containing conditions. The decreased levels of activated ERK and Akt were restored by the addition of PDGF. Inhibition of phosphorylated-ERK and Akt resulted in renewed susceptibility to cell death. These results indicate that failure of signal transduction of oncogenic Ras by the deficiency of growth factors such as PDGF causes v-Ha-Ras-dependent apoptosis.

Androstadienes↗

Construction of a new multi-turn time-of-flight mass spectrometer.

A new type of multi-turn time-of-flight mass spectrometer was constructed, consisting of four cylindrical electric sectors and 28 electric quadrupole lenses, the size of the vacuum chamber being 60 x 70 x 20 cm. It was demonstrated that the mass resolution can be increased according to the number of cycles of the ions through the ion optical system.

Mass Spectrometry↗

Dissociation study of tellurium cluster ions, Te(n)(+) (n = 25-85) using secondary ion mass spectrometry.

Dissociation pathways of tellurium clusters, Te(n)(+) (n = 25-85), were investigated by secondary ion mass spectrometry. Positively charged ions were generated from a tellurium sheet by bombardment with 10 keV xenon ion beam. Mass analyses of cluster ions were performed using a grand-scale sector mass spectrometer. In the first field-free region, Te(n)(+) (n = 25-80) had a large dissociation probability with five- and six-atom emission and Te(n)(+) (n = 50-85) had a slightly large dissociation probability with 10- and 11-atom emission. Five- and six-atom dissociation in the second field-free region could be also observed. These results were most likely due to the cluster emission processes for Te(n)(+), although sequential atom emission and cluster emission could not be distinguished by this type of experiments.

Spectrometry, Mass, Secondary Ion↗

Urethral obstruction in patients with nighttime wetting: urodynamic evaluation and outcome of surgical incision.

The aim of this study was to investigate urodynamic findings and the outcome of surgical incision in patients with nighttime wetting due to urethral obstruction. A total of 239 patients with nighttime wetting (157 males and 82 females; mean age, 8.7; range, 4-18 years) was studied. One hundred and ten patients had monosymptomatic enuresis alone and 129 both nighttime wetting and daytime symptoms, that is, the majority was not simple bedwetters, but had signs of bladder overactivity. All patients were first treated with bladder training and fluid intake after dinner was restricted. The non-responders were then treated with tricyclic antidepressants, anticholinergics, or intra-nasal desmopressin and conditioning therapy. Ninety-seven patients who did not respond to these conventional treatments were investigated by voiding cystourethrography, bougie à boule, and urodynamic study. Urethral obstruction was noted in 34 patients (14.2%); posterior urethral valves in three males, ring stricture of the bulbar urethra in 26 males and distal urethral stenosis in five females. Detrusor instability was noted in 30 (94%) of 32 patients. Three patients had <15 mL/s of maximum flow rate and none had post-void residual urine. Pressure at maximum flow (PQ(max)) was 106.5 +/- 26.3 cm H(2)O in pressure/flow study. After surgery, nighttime wetting was cured in 25 patients (73.5%), improved in four (11.8%). Detrusor instability disappeared in six of 16 patients studied (37.5%) and improved in 8 (50%), and PQ(max) decreased significantly after operation (P = 0. 0034). In conclusion, most of the patients with urethral obstruction have detrusor instability and high pressure voiding, and these conditions improved after operation.

Adolescent↗