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Biomedical subjects

K Ogita

Publications and source records attributed to K Ogita.

At least 19 recordsLinked to original sources
PubMed2006

Transient local overexpression of human vascular endothelial growth factor (VEGF) in mouse feto-maternal interface during mid-term pregnancy lowers systemic maternal blood pressure.

The effect on maternal circulation of transient human vascular endothelial growth factor (VEGF) (165) cDNA transfection into the mouse feto-maternal interface at day 14.5 post coitus (p.c.) using a hemagglutinating virus of Japan-envelope (HVJ-E) vector system is reported. On day 15.5 p.c., Western blotting clearly showed overexpression of 18 kD VEGF protein in the uterus. After VEGF transfection, the blood pressure was significantly lowered for 48 hours. On day 17.5 p.c., the blood pressure returned to the control level. Proteinuria was not observed after VEGF transfection. No preterm birth was observed during the course of pregnancy after the transfection procedure. After 24 hours of transfection, human VEGF was not detectable and the mouse VEGF level was similar to that in peripheral blood. However, the soluble fms-like tyrosine kinase (Flt)-1 concentration was significantly lower in VEGF-transfected mice. These results suggest that extraamniotic VEGF overexpression lowered the systemic blood pressure without altering the VEGF concentration in the peripheral blood. Local overexpression of VEGF may become a novel treatment for pregnancy-related disorders such as hypertension complicated-pregnancy and preeclampsia.

Animals↗
PubMed2005

Endoscopic diverticulotomy for symptomatic pediatric esophageal diverticula.

There have so far been few reports on esophageal diverticulum in children. We experienced two symptomatic pediatric cases with esophageal diverticulum. Our cases manifested high fever and dysphagia with chest pain during swallowing. The patients underwent endoscopic diverticulotomy. The septum between the diverticulum and the esophagus was cut using the argon plasma coagulation (APC 3000) system. We recommend an endoscopic diverticulotomy as an effective treatment modality for such symptomatic cases.

Adolescent↗
PubMed2004

Modulation of activator protein 1/DNA binding activity by acoustic overstimulation in the guinea-pig cochlea.

Changes in gene expression are part of the homeostatic machinery with which cells respond to external stimuli or assaults. The activity of the early response transcriptional factor activator protein-1 (AP-1) can be modulated by a variety of environmental stimuli including those that alter the cellular oxidation/reduction status. This study investigates the activation of AP-1/DNA binding in the guinea-pig cochlea in response to acoustic overstimulation which produces reactive oxygen species. Electrophoretic mobility shift assays revealed that binding of AP-1 to its radiolabeled oligonucleotide probe markedly changed in nuclear extracts of inner ear tissues following intense noise exposure (4 kHz octave band, 115 dB, 5 h). AP-1/DNA binding increased in the organ of Corti and the lateral wall tissues immediately after the exposure, returning to near-baseline levels 5 h later. At 15 h after noise, a second peak of binding activity occurred in the organ of Corti whereas stria vascularis showed a lesser but more sustained activity. Binding in nuclear extracts from the spiral ganglion did not change. Incubation of nuclear extracts with antibodies against Fos/Jun family proteins prior to a supershift assay showed Fra-2 as a major component of the AP-1 complex immediately after the noise exposure. In the organ of Corti, Fra-2 immunoreactivity was localized to the middle turn, i.e. the region which is most affected by the 4-kHz octave band exposure. The results suggest the modulation of gene expression via the activation of AP-1 as a consequence of noise trauma but also demonstrate differential responses in cochlear tissues.

Acoustic Stimulation↗
PubMed2004

Real-time monitoring for detecting rejection using strain gauge force transducers in porcine small bowel transplantation.

PURPOSE: The clinical results of small bowel transplantation (SBT) have not been satisfactory mainly because of the immunological barrier. It is important to detect the presence of and to perform adequate treatment of rejection as early as possible to improve graft survival. Therefore, we have established a pig model to monitor graft motility as a means to detect rejection in real time. METHODS: Orthotropic SBT was performed in 25 pigs using FK-506 (0.05 to 0.1 mg/kg/d) immunosuppression. The interdigestive motor patterns were evaluated using strain gauge force transducers (SG). Seven pigs without SBT were treated as controls (C). Animals that displayed migrating motor complex (MMC) activity as evidenced by duration, amplitude, and interval in the graft were alive more than 10 days with adequate oral feeding: the functional graft (FG) group. In contrast the rejection (R) group did not show these activities on data recorded within 10 days before death due to rejection. RESULTS: The FG group showed MMC propagated throughout the graft with all parameters almost the same as the control group except for the duration. In contrast, all parameters in the group R were significantly lower than those in group FG, suggesting that group R motility was obviously impaired by rejection. CONCLUSIONS: The SG method may afford real-time monitoring of transplanted bowel motility that could be useful to detect rejection after SBT.

Animals↗
PubMed2004

Immunosuppressive effect of nucleoside-nucleotide-free diet in rat allogeneic small intestinal transplantation.

BACKGROUND: We evaluated the effects of nucleosides (NS) and nucleotides (NT) on the rejection of rat allogeneic small intestinal transplants. METHODS: A 2-cm segment of jejunum from fetal Fischer rats (RT-1(lvl)) was transplanted at day 19 of gestation into the abdominal wall of 7-week-old Lewis rats (RT-1(l)) by a nonvascular technique. Two weeks before transplantation, recipient rats were separated into an NS-NT-free group and an NS-NT-supplemented group. At 2 days after transplantation, histologic study of the grafts was performed with hematoxylin-eosin staining and interleukin-2 (IL-2) production estimated in recipient blood using an ELISA method. The morphologic findings were graded in a blind fashion on a scale of 0 to 4, with 0 indicating an intact intestinal structure. RESULTS: Mean plasma IL-2 levels of the NS-NT-free group were significantly lower than those of the NS-NT-supplemented group. The mean rejection score of the NS-NT-free group was also significantly lower than that of the NS-NT-supplemented group. CONCLUSIONS: Administration of an NS-NT-free diet reduces acute rejection in rat small intestinal transplantations.

Animals↗
PubMed2003

Effects of omega-3 fatty acids in rat allogenic small intestinal transplantation.

The aim of this study was to estimate the effect of omega-3 fatty acids on the recipient and graft immune response after rat allogenic small intestinal transplantation. Seven-week-old Lewis rats were randomly assigned to one of three groups according to the diet received: an FO group (fish oil supplemented), an SB group (soy bean oil supplemented) or a control group (normal rat chow). The recipient Lewis rats were each given their respective group diet for 12 days, and then, on the 19th day of gestation, a 2 cm jejunum from the donor fetal Fischer rat was transplanted into the abdominal wall of the recipient rats using a non-vascular anastomotic technique. The recipient rats were killed on day 2 after transplantation, and the recipient plasma IL-2, IFN-gamma and IL-1 beta levels were determined. In addition, the histological findings of the graft were analyzed. The cytokine levels of the FO group were significantly lower than the other two groups. In order to determine the grade of rejection, the morphological findings were blindly graded on a scale of 0-4. The mean grade of the FO group was also significantly lower than the other two groups. Omega-3 fatty acids are therefore considered to have an immunosuppressive effect on rat allogenic small intestinal transplantation based on the recipient plasma IL-1 beta, TNF and IL-2 levels and the histological findings of the grafts.

Animals↗
PubMed2003

Molecular regulation of the oxytocin receptor in peripheral organs.

The oxytocin receptor belongs to the G-protein-coupled seven transmembrane receptor superfamily. Its main physiological role is regulating the contraction of uterine smooth muscle at parturition and the ejection of milk from the lactating breast. Oxytocin receptor expression is observed not only in the myometrium and mammary gland but also in the endometrium, decidua, ovary, testis, epididymis, vas deferens, thymus, heart and kidney, as well as in the brain. The expression profile shows a tissue-specific as well as a stage-specific pattern. The oxytocin receptor gene is a single-copy gene consisting of four exons and three introns, localized at 3p25-3p26.2 in the human chromosome. In transfection studies using a fusion construct containing the promoter region of the oxytocin receptor gene inserted in a reporter plasmid, neither proinflammatory cytokines nor oestrogen directly activate the gene. The nuclear fractions from up-regulated (term myometrium) and down-regulated (non-pregnant myometrium) tIssues show differential patterns of protein binding to the 5'-flanking region, and a human homologue of chicken MafF has been cloned as a term-myometrium-specific oxytocin receptor modulator. The oxytocin receptor gene appears to be highly methylated. Methylation around intron 1 and in intron 3 might contribute to tIssue-specific suppression of the gene. The oxytocin receptor is also regulated by desensitization, whose mechanism appears to involve loss of ligand-binding activity of the protein as well as suppression of the oxytocin receptor mRNA transcription. These findings taken together indicate that the oxytocin receptor is regulated in a very complicated manner, and the transcriptional regulatory elements critical for this regulation should be investigated further.

Animals↗
PubMed2001

DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression.

In the human oxytocin receptor (OTR) gene, there is a CpG island from 140 bp upstream to 2338 bp downstream of the transcription start site (TSS). We investigated whether the methylation state of this region affects the transcription of the OTR gene. HepG2 derived from human hepatoblastoma, in which OTR gene transcription was suppressed, was treated with a demethylating agent, 5-azacytidine (Aza-C) for 2 days. Semiquantitative RT-PCR indicated that OTR mRNA was significantly increased by Aza-C treatment in a dose-dependent manner. We estimated the level of methylation within the CpG islands of the OTR gene in peripheral blood leukocytes, nonpregnant uterine myometrium, term uterine myometrium and liver. A 1.5-kb region located 5' upstream of the translation start site was divided into four fragments. Each was amplified by PCR after complete digestion with methylation-sensitive restriction enzyme HpaII. The amount of PCR products was largest in the liver, suggesting that this CpG island in the OTR gene is most highly methylated in liver, where the gene is always inactivated. We compared the effect of in vivo methylation of the CpG island on transcriptional activity of an OTR-reporter plasmid. The reporter gene activity of expression plasmid -2860/+1342-GL3, containing the CpG island, in HepG2 cells was suppressed to 30.6% of the control level after methylation with SssI methylase, while that of -2840/+144-GL3, without the CpG island was suppressed only to 81.4%. The deletion of the segment (MT2) where the level of methylation was most different between liver and uterus (-2860/+1342(del)MT2-GL3) rescued the suppression rate to 68.0%. These results indicate that the methylation of the CpG island in the human OTR gene promoter suppressed its transcription at least in liver and may regulate tissue specific gene expression among organs.

Azacitidine↗
PubMed2001

Relationship between plasma insulin concentration and plasma remnant lipoprotein response to an oral fat load in patients with type 2 diabetes.

OBJECTIVES: The goal of this study was to evaluate the relative effects of hyperglycemia and hyperinsulinemia on postprandial remnant lipoprotein (RLP) concentrations in newly diagnosed type 2 diabetics. BACKGROUND: Increases in fasting RLP concentration have been described in type 2 diabetics, as well as in insulin-resistant nondiabetics. Given the atherogenicity of RLPs, we have extended these observations by assessing postprandial RLP concentrations and observing that hyperglycemia was necessary for the increase in RLP concentrations. METHODS: Patients with type 2 diabetes were subdivided on the basis of their plasma insulin response to oral glucose into hyperinsulinemic (H-DM) and normoinsulinemic (N-DM) groups of 15 patients each. Plasma triglyceride (TG), RLP-TG and RLP cholesterol (RLP-C) concentrations were determined before and 2 and 4 h after an oral fat load in these patients and 10 control (CTL) subjects. RESULTS: Plasma TG, RLP-TG and RLP-C concentrations peaked 2 h after the fat load in the CTL group, returning to baseline within 4 h. In contrast, concentrations of these variables increased throughout the 4-h study in both groups of patients with type 2 diabetes. Total integrated plasma RLP-TG and RLP-C responses above baseline after the oral fat load were significantly higher in the H-DM group compared with the CTL (p = 0.019 and 0.009, respectively) or N-DM (p = 0.026 and 0.029, respectively) groups. Post-heparin lipoprotein lipase activities and apo E phenotypes were similar in the H-DM and N-DM groups. CONCLUSIONS: Remnant lipoprotein response to an oral fat load is significantly increased in hyperinsulinemic patients with type 2 diabetes. These changes may increase the risk of coronary heart disease in these individuals.

Adult↗
PubMed2001

Differential in vitro degradation of particular Fos family members expressed by kainic acid in nuclear and cytosolic fractions of murine hippocampus.

Mice were injected with kainic acid (KA) at a convulsive dose, followed by homogenization of the hippocampus in the presence of different protease and phosphatase inhibitors, and subsequent preparation of nuclear and cytosolic fractions. An intraperitoneal injection of KA resulted in marked expression of particular Fos family members, including c-Fos, Fra-2, and Fos-B, but not Fra-1 proteins, in both fractions 2 to 18 h after administration. These fractions were individually incubated at 30 degrees C for 1 to 18 h for determination of in vitro degradation. Similarly rapid degradation was seen with c-Fos protein between nuclear fractions obtained 2 and 18 h after administration, while no significant degradation was found for c-Fos protein in cytosolic fractions obtained 2 h after administration during incubation. By contrast, in vitro incubation led to rapid degradation of c-Fos protein in cytosolic fractions obtained 18 h after administration. Degradation profiles were peculiar to each member protein in nuclear and cytosolic fractions obtained 2 and 18 h after administration. Dialysis prevented degradation of c-Fos protein in nuclear fractions without markedly affecting that in cytosolic fractions in a manner independent of the time after administration. The addition of inhibitors for phosphatases, but not for proteases, accelerated the degradation of c-Fos protein in nuclear fractions previously dialyzed. These results suggest that in vivo KA signals may modulate heterologous machineries responsible for breakdown of each Fos family member in a unique manner in nuclear fractions, rather than cytosolic fractions, of murine hippocampus.

Animals↗
PubMed2001

Decrease in level of APG-2, a member of the heat shock protein 110 family, in murine brain following systemic administration of kainic acid.

APG-2 belongs to the heat shock protein 110 family. Although kainic acid (KA)-induced seizures are known to elicit expression of inducible heat shock protein 70 (HSP70) in the brain, no investigation has been carried out on the APG-2 level after excitatory amino acid-induced seizures. By means of an immunoblot assay, we determined the levels of HSP70 and APG-2 in discrete brain structures of mice after a single intraperitoneal injection of KA or N-methyl-D-aspartic acid (NMDA). APG-2 level was significantly decreased in frontal cortex, hippocampus, and striatum three days after the administration of KA, while HSP70 level was increased in these regions following the administration. In any of these regions, APG-2 levels were returned to the control levels 10 days after the administration. However, no significant changes were observed in levels of both HSP70 and APG-2 in hypothalamus, midbrain, medulla-pons, and cerebellum of the mice. By contrast, NMDA administration did not significantly affect both levels in any of the regions examined. These findings indicate that the transient decrease in APG-2 expression is one of the intracellular events elicited by signals peculiar to KA, but not by those peculiar to NMDA, in telencephalon of murine brain.

Animals↗
PubMed2001

Characterization with [3H]quisqualate of group I metabotropic glutamate receptor subtype in rat central and peripheral excitable tissues.

Radioligand binding studies were performed to label metabotropic glutamate receptor (mGluR) in rat brain synaptic membranes using [3H]quisqualic acid (QA) synthesized in our laboratory as a radioligand. In the presence of ionotropic glutamate receptor (iGluR) agonists, including N-methyl-D-aspartic (NMDA), DL-alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic (AMPA) and kainic acids (KA), at concentrations maximally effective in displacing each receptor binding, the agonists for group I mGluR subtype (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) and (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) more potently displaced [3H]QA binding in a concentration-dependent manner than their absence. The addition of these three iGluR agonists did not significantly affect potencies of (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) and L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) to displace [3H]QA binding. Scatchard analysis revealed that [3H]QA binding consisted of a single component with a maximal number of binding sites (B(max)) of 431.6 fmol/mg protein and a dissociation constant (K(d)) of 50.9 nM, in the presence of the three iGluR agonists. [3H]QA binding was markedly inhibited by GTP and its analogues; but not by GDP, GMP and ATP, under these conditions. Inhibition by GTP was seen in all central structures examined, but [3H]QA binding was not detectable in peripheral tissues, such as pituitary and adrenal glands. Neither reverses transcription polymerase chain reaction nor immunoblotting analysis demonstrated the expression of mGluR1 and mGluR5 subunits in the aforementioned two peripheral tissues. These results suggest that [3H]QA indeed labels group I mGluR subtype functionally coupled to GTP binding protein in rat brain synaptic membranes under the experimental conditions employed. Group I mGluR subtype seems to be selectively distributed in central structures but not in pituitary and adrenal glands.

Adrenal Glands↗
PubMed2001

Effects of glutathione depletion by 2-cyclohexen-1-one on excitatory amino acids-induced enhancement of activator protein-1 DNA binding in murine hippocampus.

We have investigated the role of glutathione in mechanisms associated with excitatory amino acid signaling to the nuclear transcription factor activator protein-1 (AP1) in the brain using mice depleted of endogenous glutathione by prior treatment with 2-cyclohexen-1-one (CHX). In the hippocampus of animals treated with CHX 2 h before, a significant increase was seen in enhancement of AP1 DNA binding when determined 2 h after the injection of kainic acid (KA) at low doses. The sensitization to KA was not seen in animals injected with CHX 24 h before, in coincidence with the recovery of glutathione contents to the normal levels. By contrast, CHX did not significantly affect the potentiation by NMDA of AP1 binding under any experimental conditions. Prior treatment with CHX resulted in facilitation of behavioral changes induced by KA without affecting those induced by NMDA. These results suggest that endogenous glutathione may be at least in part involved in molecular mechanisms underlying transcriptional control by KA, but not by NMDA, signals of cellular functions.

Animals↗
PubMed2001

Inhibition of vesicular glutamate storage and exocytotic release by Rose Bengal.

It had been thought that quantal size in synaptic transmission is invariable. Evidence has been emerging, however, that quantal size can be varied under certain conditions. We present evidence that alteration in vesicular [(3)H]L-glutamate (Glu) content within the synaptosome (a pinched-off nerve ending preparation) leads to a change in the amount of exocytotically released [(3)H]Glu. We found that Rose Bengal, a polyhalogenated fluorescein derivative, is a quite potent membrane-permeant inhibitor (K(i) = 19 nM) of glutamate uptake into isolated synaptic vesicles. This vesicular Glu uptake inhibition was achieved largely without affecting H(+)-pump ATPase. We show that various degrees of reduction elicited by Rose Bengal in [(3)H]Glu in synaptic vesicles inside the synaptosome result in a corresponding decrease in the amount of [(3)H]Glu released in a depolarization- (induced by 4-aminopyridine) and Ca(2+)-dependent manner. In contrast, fluorescein, the halogen-free analog of Rose Bengal, which is devoid of inhibitory activity on vesicular [(3)H]Glu uptake, failed to change the amount of exocytotically released [(3)H]Glu. These observations suggest that glutamate synaptic transmission could be altered by pharmacological intervention of glutamate uptake into synaptic vesicles in the nerve terminal, a new mode of synaptic manipulation for glutamate transmission.

4-Aminopyridine↗
PubMed2001

Triglyceride-rich lipoprotein cholesterol exceeds low-density lipoprotein cholesterol in hypertriglyceridemia patients.

The atherogenicity of triglyceride-rich lipoprotein has been revealed. This study was performed to explore the clinical importance of triglyceride-rich lipoprotein by measuring its cholesterol content and comparing it with other lipoprotein fractions. Blood samples were obtained from 103 patients whose fasting plasma triglyceride concentration exceeded 300 mg/dl. The cholesterol monitor using the technique of high-performance liquid chromatography was used for the measurement of their plasma cholesterol concentrations and the determination of cholesterol distribution among lipoprotein fractions. This monitor showed 4 peaks: large-triglyceride-rich lipoprotein, small-triglyceride-rich lipoprotein, low-density lipoprotein, and high-density lipoprotein. Total cholesterol increased with increasing triglyceride. The increment of total cholesterol was nearly equal to that of small-triglyceride-rich lipoprotein cholesterol. Small-triglyceride-rich lipoprotein cholesterol exceeded low-density lipoprotein cholesterol where plasma triglyceride concentration was over 500 mg/dl. In conclusion, triglyceride-rich lipoprotein may be clinically important for hypertriglyceridemic patients as a source of cholesteryl ester in arteriosclerotic plaques, and increased triglyceride-rich lipoprotein cholesterol may be used as a basis for hypertriglyceridemia atherogenicity. Our study suggests that hypertriglyceridemia should be treated to prevent arteriosclerotic disease.

Apolipoproteins E↗