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Biomedical subjects

T Murata

Publications and source records attributed to T Murata.

At least 163 records · Page 9Linked to original sources
PubMed2000

Angiogenesis and its regulation: roles of vascular endothelial cell growth factor.

Neovascularization is well known to occur in human atherosclerotic plaques, proliferative retinopathies, and malignant neoplasias. However, its pathophysiologic roles and mechanisms still remain unclear. In this study, histochemical examination of atherosclerotic plaques showed that vascular endothelial cell growth factor (VEGF) was expressed by the smooth muscle cells and foamy macrophages in the atherosclerotic intimas. The number of VEGF-positive cells was positively correlated with the number of intimal blood vessels. Moreover, VEGF gene transfer into rabbit carotid arteries using the hemagglutinating virus of Japan (HVJ)-liposomes showed that VEGF overexpression could induce the angiomatoid proliferation. In diabetic rats, VEGF was overexpressed in diabetic retinas, and thus the local overexpression of VEGF seemed to play an important role in the development of blood-retinal barrier breakdown in simple diabetic retinopathy. These results indicated that the VEGF can act as a local and endogenous regulator of endothelial cell functions and that VEGF induces the neovascularization under pathophysiologic conditions. On the other hand, the transfer of a decoy for the cis-element in the promoter region of the angiogenic factors would be an effective method for regulating angiogenesis, because other angiogenic factors' expression promoted by such cis-element could be simultaneously suppressed. Therefore, this method may supply a useful therapeutic tool for the regulation of pathologic angiogenesis.

Animals↗
PubMed2000

Photoregulation of asymmetric cell division followed by rhizoid development in the fern Ceratopteris prothalli.

Strap-shaped prothalli of CERATOPTERIS: richardii grown in the dark have an apical meristem, a subapical elongation zone and a basal growth cessation zone [Murata et al. (1997) Plant Cell Physiol. 38: 201]. When the dark-grown prothalli were irradiated with continuous white light, marginal cells of the elongation zone divided asymmetrically, and the resulting smaller cells developed into rhizoids. The asymmetric division was also induced by brief irradiation of red light. The effect of red light was cancelled by subsequent irradiation of far-red light, indicating that the asymmetric division was regulated by phytochrome. Since the response to red light was not observed at 10(1) J m(-2) and saturated at 10(2) J m(-2) and the response is photoreversible by far-red light, the photoresponse was classified as a low-fluence response of phytochrome. Although the asymmetric division was induced by brief irradiation of red light, continuous irradiation of white, blue or red light was necessary to induce rhizoid growth. These results indicate that asymmetric division and subsequent cell growth are independently regulated by light in CERATOPTERIS: prothalli.

Cell Division↗
PubMed2000

Hypoxic but not ischemic neurotoxicity of free radicals revealed by dynamic changes in glucose metabolism of fresh rat brain slices on positron autoradiography.

Dynamic changes in the regional cerebral glucose metabolic rate induced by hypoxia/reoxygenation or ischemia/reperfusion were investigated with a positron autoradiography technique. Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [18F]FDG uptake in the slices were obtained. In the case of loading hypoxia (oxygen deprivation)/pseudoischemia (oxygen and glucose deprivation) for various periods of time, the net influx constant (K) of [18F]FDG at preloading and after reoxygenation/pseudoreperfusion (post-loading) was quantitatively evaluated by applying the Patlak graphical method to the image data. Regardless of the brain region, with hypoxia lasting > or =20 minutes, the postloading K value was decreased compared with the unloaded control, whereas with pseudoischemia of < or =40 minutes, approximately the same level as the unloaded control was maintained. Next, the neuroprotective effect against hypoxia/pseudoischemia loading induced by the addition of a free radical scavenger or an N-methyl-D-aspartate (NMDA) antagonist was assessed by determining whether a decrease in the postloading K value was prevented. Whereas with 20-minute hypoxia, both agents exhibited a neuroprotective effect, in the case of 50-minute pseudoischemia, only the NMDA antagonist did so, with the free radical scavenger being ineffective. These results demonstrate that hypoxia causes irreversible neuronal damage within a shorter period than ischemia, with both free radicals and glutamate suggested to be involved in tandem in the neurotoxicity induced by hypoxia, whereas glutamate alone is involved in ischemic neurotoxicity.

Animals↗
PubMed2000

Mitochondrial distribution and function in herpes simplex virus-infected cells.

In this study, mitochondria migrated to a perinuclear region in the cytoplasm in herpes simplex virus (HSV)-infected cells. HSV infection did not promote the expression of cytochrome c oxidase subunit 2 but did promote that of stress-responsive HSP60, both of which are known to be components of mitochondria. The levels of cellular ATP and lactate and mitochondrial membrane potential were maintained for at least 6 h but decreased at the late stage of infection. It was also found that the UL41 and UL46 gene products, both of which are known to be tegument proteins, accumulated in the perinuclear region. The clustering of mitochondria and the accumulation of tegument proteins were completely blocked by the addition of nocodazole and vinblastine. These results suggest that mitochondria respond to the stimulation of HSV infection, migrating with tegument proteins along microtubules to a site around the nucleus, and maintain function until at least the middle stage of infection.

Animals↗
PubMed2000

Molecular analysis of the folC gene of Pseudomonas aeruginosa.

We have cloned the Pseudomonas aeruginosa folC gene coding for folylpolyglutamate synthetase-dihydrofolate synthetase, which was located between the trpF and purF loci, and determined the nucleotide sequence of the folC gene and its flanking region. The deduced amino acid sequence of P. aeruginosa FolC was highly homologous to that of Escherichia coli FolC. The cloned gene complemented E. coli folC mutations and was found to encode both folylpolyglutamate synthetase and dihydrofolate synthetase activities. The gene organization around the folC gene in P. aeruginosa was completely conserved with that in E. coli; the accD gene was located upstream of the folC gene, and dedD, cvpA and purF genes followed the folC gene in this order. The gene arrangement and the result of the promoter activity assay suggested that the P. aeruginosa accD and folC genes were co-transcribed.

Acetyl-CoA Carboxylase↗
PubMed2000

Adaptation of laser-Doppler flowmetry to measure cerebral blood flow in the fetal sheep.

The purpose of this study was to devise a means to use laser-Doppler flowmetry to measure cerebral perfusion before birth. The method has not been used previously, largely because of intrauterine movement artifacts. To minimize movement artifacts, a probe holder was molded from epoxy putty to the contour of the fetal skull. A curved 18-gauge needle was embedded in the holder. At surgery, the holder, probe, and skull were fixed together with tissue glue. Residual signals were recorded after fetal death and after maternal death 1 h later. These averaged <5% of baseline flow signals, indicating minimal movement artifact. To test the usefulness of the method, cerebral flow responses were measured during moderate fetal hypoxia induced by giving the ewes approximately 10% oxygen in nitrogen to breathe. As fetal arterial PO(2) decreased from 21.1 +/- 0.5 to 10.7 +/- 0.4 Torr during a 30-min period, cerebral perfusion increased progressively to 56 +/- 8% above baseline. Perfusion then returned to baseline levels during a 30-min recovery period. These responses are quantitatively similar to those spot observations that have been recorded earlier using labeled microspheres. We conclude that cerebral perfusion can be successfully measured by using laser-Doppler flowmetry with the unanesthetized, chronically prepared fetal sheep as an experimental model. With this method, relative changes of perfusion from a small volume of the ovine fetal brain can be measured on a continuous basis, and movement artifacts can be reduced to 5% of measured flow values.

Animals↗
PubMed2000

Temporally restricted expression of transcription factor betaFTZ-F1: significance for embryogenesis, molting and metamorphosis in Drosophila melanogaster.

FTZ-F1, a member of the nuclear receptor superfamily, has been implicated in the activation of the segmentation gene fushi tarazu during early embryogenesis of Drosophila melanogaster. We found that an isoform of FTZ-F1, betaFTZ-F1, is expressed in the nuclei of almost all tissues slightly before the first and second larval ecdysis and before pupation. Severely affected ftz-f1 mutants display an embryonic lethal phenotype, but can be rescued by ectopic expression of betaFTZ-F1 during the period of endogenous betaFTZ-F1 expression in the wild type. The resulting larvae are not able to molt, but this activity is rescued again by forced expression of betaFTZ-F1, allowing progression to the next larval instar stage. On the other hand, premature expression of betaFTZ-F1 in wild-type larvae at mid-first instar or mid-second instar stages causes defects in the molting process. Sensitive periods were found to be around the time of peak ecdysteroid levels and slightly before the start of endogenous betaFTZ-F1 expression. A hypomorphic ftz-f1 mutant that arrests in the prepupal stage can also be rescued by ectopic, time-specific expression of betaFTZ-F1. Failure of salivary gland histolysis, one of the phenotypes of the ftz-f1 mutant, is rescued by forced expression of the ftz-f1 downstream gene BR-C during the late prepupal period. These results suggest that betaFTZ-F1 regulates genes associated with ecdysis and metamorphosis, and that the exact timing of its action in the ecdysone-induced gene cascade is important for proper development.

Animals↗
PubMed2000

Involvement of lipoxygenase pathway in docosapentaenoic acid-induced inhibition of platelet aggregation.

The effects of docosapentaenoic acid (DPA) on platelet aggregation and arachidonic acid metabolism were studied in comparison to those of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Collagen- or arachidonic acid-stimulated platelet aggregation was inhibited dose-dependently by n-3 fatty acids, among which DPA was the most potent inhibitor. These fatty acids inhibited U46619-induced aggregation but to almost the same extent. No effect of the acids on thrombin-induced aggregation was observed. Furthermore, these fatty acids suppressed thromboxane A2 formation by platelets which were exposed to collagen or thrombin, or by platelets to which arachidonic acid was added. In these experiments also, DPA was the most potent inhibitor, whereas DHA was the most effective inhibitor of cyclooxygenase-1 activity. DPA enhanced formation of 12-hydroxyeicosatetraenoic acid in response to collagen or from arachidonic acid by intact platelets, while the other two acids had less of an effect. These results suggest that DPA possesses potent activity for interfering with the cyclooxygenase pathway and accelerating the lipoxygenase pathway, thus inhibiting platelet aggregation most effectively.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2000

Changes in fetal plasma adenosine and xanthine concentrations during fetal asphyxia with maternal oxygen administration in ewes.

In this study, we measured fetal plasma adenosine and xanthine concentrations during and after severe asphyxia, and investigated the key issues related to oxygen therapy. Asphyxia was induced by occluding the umbilical cord for 5 minutes in 6 fetal sheep with and without the administration of oxygen to the ewe. Plasma adenosine concentration increased significantly during cord occlusion in the all fetuses, and the differences between the values in the fetuses with and without maternal oxygen administration was not significant. By 30 minutes after cord release, plasma adenosine concentration in all fetuses had returned to levels similar to those at the start of the experiment. Plasma xanthine concentration also increased during cord occlusion in all fetuses. However, 30 minutes after cord release, plasma xanthine concentration had decreased significantly in fetuses without additional oxygen, while it did not change significantly in fetuses with maternal oxygen administration. Thus, we speculated that maternal oxygen administration before fetal asphyxia may not contribute to additional ATP stores in fetal organs and may produce oxygen free radicals following asphyxia.

Adenosine↗
PubMed2000

Oxytocin receptor gene expression in rat uterus: regulation by ovarian steroids.

The present study was designed to investigate a possible role for ovarian steroids in the regulation of rat uterine oxytocin receptor (OTR) mRNA expression before labour. By using a competitive RT-PCR system, we have previously reported that parturition was associated with high levels of uterine OTR mRNA in all the animals examined. On the other hand, near term, some rats showed high OTR mRNA levels while others did not. We therefore examined the changes in OTR mRNA expression before and during prostaglandin F(2)(alpha) (PGF(2)(alpha))-induced parturition; a paradigm adopted to reduce the variation in the onset of parturition. Injection of PGF(2)(alpha) on day 18 of pregnancy significantly increased OTR mRNA expression in all the rats within 24 h of treatment, suggesting that the variation in OTR mRNA levels during spontaneous parturition may be due to the difference in the timing of the onset of parturition. The increase in OTR mRNA was significantly abolished by injection of the anti-oestrogen compound, tamoxifen. The stimulatory action of oestrogen on OTR mRNA expression was then examined in the presence or absence of ovarian factors. Pregnant rats were ovariectomized (OVX) or sham-operated on day 18 of pregnancy and either oestrogen or vehicle was administered 6 h after the surgical operation. Oestrogen increased OTR mRNA significantly in OVX rats 18 h after administration compared with sham-operated animals. Moreover, ovariectomy alone on day 18 of pregnancy increased OTR mRNA expression to a level which reached statistical significance 24 h after the operation. In addition, oestrogen treatment increased OTR mRNA levels in OVX virgin rats in which progesterone tubes were implanted for 1 week and removed 6 h before oestrogen injection. The stimulatory effect of oestrogen was not observed in rats in which the progesterone tubes were implanted for 1 week and not removed. These results suggest that the decline of progesterone is necessary for the expression of the stimulatory effects of oestrogen on uterine OTR mRNA.

Analysis of Variance↗
PubMed2000

Gastrointestinal stromal tumors of the small intestine that expressed c-kit protein.

We report two patients with gastrointestinal stromal tumors (GISTs) of the small intestine that expressed c-kit protein (CD117). One was a 68-year-old woman with epigastralgia and vomiting. A submucosal tumor of the upper jejunum was detected, and partial resection was carried out. The histology revealed a GIST negative for CD34 but positive for CD117. The other was a 42-year-old woman with progressive anemia, melena and lower abdominal pain. Intussusception was detected, and a partial resection was carried out. A submucosal tumor of the lower jejunum was noted. The histology revealed a GIST positive for both CD34 and CD117.

Adult↗
PubMed2000

Gravimorphogenesis of Cucurbitaceae plants: development of peg cells and graviperception mechanism in cucumber seedlings.

We examined the effect of microgravity on the peg formation of cucumber seedlings for clarifying the mechanism of gravimorphogenesis in cucurbitaceous plants. The spaceflight experiments verified that gravity controls the formation of peg, hypocotyl hook and growth orientation of cucumber seedlings. Space-grown cucumber developed a peg on each side of the transition zone of the hypocotyl and root, indicating that on the ground peg formation is regulated negatively by gravity (Takahashi et al. 2000). It was found that the auxin-regulated gene, CS-IAA1, was strongly expressed in the transition zone where peg develops (Fujii et al. 2000). In the seedlings grown horizontally on the ground, CS-IAA1 transcripts were much abundant on the lower side of the transition zone, but no such differential expression of CS-IAA1 was observed in the space-grown cucumber (Kamada et al. 2000). These results imply that gravity plays a role in peg formation through auxin redistribution. By the negative control, peg formation on the upper side of the transition zone in the horizontally growing seedlings might be suppressed due to a reduction in auxin concentration. The threshold theory of auxin concentration accounted for the new concept, negative control of morphogenesis by gravity (Kamada et al. 2000). Anatomical studies have shown that there exists the target cells destined to be a peg and distinguishable at the early stage of the growth. Ultra-structural analysis suggested that endoplasmic reticulum develops well in the cells of the future peg. Furthermore, it was found that reorganization of cortical microtubules is required for the change in cell growth polarity in the process of peg formation. The spaceflight experiment with cucumber seedlings also suggested that in microgravity positive hydrotropic response of roots occurred without interference by gravitropic response (Takahashi et al. 1999b). Thus, this spaceflight experiment together with the ground-based studies has shown that cucumber seedling is an ideal for the study of gravimorphogenesis, hydrotropism and their interaction. Although peg formation is seen specifically in cucurbitaceous seedlings, it involves graviperception, auxin transport and redistribution and cytoskeletal modification for controlling cell growth polarity. This system could be a useful model for studying important current issues in plant biology.

Cucumis sativus↗
PubMed2000

Advanced glycation end products in diabetic corneas.

PURPOSE: Corneal complications are often associated with diabetes mellitus and can be vision threatening. Corneas in diabetic patients are exposed to increased glucose concentration despite cornea's avascular property, and this condition may contribute to the accumulation of advanced glycation end products (AGEs). The focus of this study was to examine the role of AGEs in the pathogenesis of diabetic keratopathy. METHODS: An anti-AGE monoclonal antibody (6D12), which recognizes a N(epsilon)-carboxymethyl lysine (CML)-protein adduct as an epitope, was prepared. Immunohistochemical localization of CML was examined in human age-matched diabetic and nondiabetic corneas (8 of each). In vitro, type I collagen-, type IV collagen-, or laminin-coated 96-well plates were glycated by glucose-phosphate. In some experiments, aminoguanidine was present in the incubation mixture. The amounts of CML-protein adducts in the extracellular matrix (ECM) were determined by enzyme-linked immunosorbent assay using 6D12. SV40-immortalized human corneal epithelial cells were seeded onto modified or unmodified ECM in 96-well plates and allowed to attach for 3 hours. Attached cells were fixed, and the areas of attached cells in each condition were measured. Attached cells without fixation were removed, and cell number was counted. RESULTS: In all of the 8 diabetic corneas, CML immunoreactivity was observed in the epithelial basement membrane, whereas CML immunoreactivity was not found in the corresponding area in 7 of 8 nondiabetic corneas. In vitro, nonenzymatic glycation of laminin on the culture dish attenuated adhesion and spreading of corneal epithelial cells. The presence of amninoguanidine in the incubation mixture during glycation inhibited CML formation and promoted the adhesion and spreading of corneal epithelial cells in a dose-dependent manner. CONCLUSIONS: The accumulation of AGEs on the basement membrane, particularly on laminin, may play a causative role in the corneal epithelial disorders of diabetic patients.

Aged↗
PubMed2000

Application of laser Doppler flowmetry to measure cerebral microvascular perfusion in the fetal sheep.

Laser Doppler flowmetry (LDF) has been used to measure flow in various organs of the adult, but has not been applied to the mammalian fetus. The purpose of this study was to apply LDF to measure cerebral blood flow of the fetal sheep and to assess the possible errors and artifacts of the method caused by myometrial, fetal, and maternal movements. By three days after probe placement, the flow signal had decreased 55% from initial post surgical readings and thereafter it became stable. During fetal hypoxia, the signal increased 48% and during hypercarbia it increased 59%. After fetal death, the signal decreased to 48% of control level. After maternal death, it decreased to 9% and electrical zero could not be reached. LDF is useful to measure changes of fetal cerebral microvascular perfusion because it can provide continuous signals but care is required in data handling and probe fixation when used for the mammalian fetus.

Animals↗
PubMed2000

Regional cerebral blood flow in the patients with depressive disorders.

Regional Cerebral blood flow (rCBF) and metabolism in major depression have been studied intently. Those studies are expected to reveal the mechanisms of the mood disorders, and also to give us valuable informations that the specific brain regions participating mood regulation. However, the data still have been inconsistent. In the present study we measured rCBF in patients with major depression and depressive state using xenon-CT CBF method. There is a tendencies that the rCBF values of normal control is the highest, and those of major depression is the lowest in most of the regions. The rCBF values in the patients with major depression are significantly lower than those in normal control in the right anterior frontal cortex, temporal cortex, putamen and thalamus. We also measured rCBF before and 90 minutes after giving calcium antagonist nilvadipine (4 mg, p.o.) in those subject. There is a tendency that nilvadipine increased in rCBF in normal control, however, it decreased in rCBF in major depression.

Adult↗
PubMed2000

[Molecular mechanism of alpha-herpesvirus proliferation].

Among members of the subfamily alpha herpesviruses, herpes simplex virus (HSV) is one of the most well-studied and the most important human pathogen. HSV is reported to possess the large, double-stranded DNA genome which contains at least 80 genes. Recent studies have revealed the functions and roles of many gene products in HSV-infected cells. This article briefly reviews the results of these studies relating to HSV replication mechanism in cells and latent infection in central nerve system (CNS).

Herpes Simplex↗