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Biomedical subjects

T Murata

Publications and source records attributed to T Murata.

At least 235 records · Page 13Linked to original sources
PubMed1999

Sharing of receptor subunits and signal transduction pathway between the IL-4 and IL-13 receptor system.

In this review, we summarize the subunit structure of the interleukin (IL)-4 and IL-13 receptor system and the molecular mechanism of signals through the cytokine receptor systems. We have demonstrated that two different forms of IL-4R exist, classical and alternative. Classical IL-4R is predominantly expressed in hematopoietic cells and consists of IL-4R p140 (beta) and IL-2R gamma (gamma c) chains. The alternative form of IL-4R is predominantly expressed in nonhematopoietic cells and consists of IL-4R beta and IL-13R alpha' chains. Moreover, the alternative form of IL-4R is also used as a functional component in the IL-13R complex. For signal transduction through IL-4R and IL-13R, we have demonstrated that in nonhematopoietic cells, Janus protein tyrosine kinase (JAK) 2 is phosphorylated and activated instead of JAK3 tyrosine kinase. While JAK3 is required for signal transducer and activator of transcription-6 (STAT6) activation in hematopoietic cells, we recently demonstrated that in nonhematopoietic cells JAK2 is required for STAT6 activation for the alternative form of IL-4R. Thus, a major difference exists between hematopoietic and nonhematopoietic cells with regard to structure and signal transduction through the IL-4R and IL-13R systems.

Hematopoietic System↗
PubMed1999

Koan Ogata's obtainment of Dutch scientific books.

Koan Ogata (1810-1863), a medical doctor in Osaka, is renowned for his contribution to the spread of vaccination and for his private school Teki-juku, a Rangaku school where education of Western learning was done by means of the Dutch language. In many letters collected in "Ogata Koan no Tegami" (1980-1996), he asked help for obtaining various Dutch scientific books to his former students, Shuhei Mitsukuri and Ryotei Takeya during several years around 1859: Mitsukuri was a staff member of the Foreign Affairs and intermittently Bansho Shirabesho (Institute for Western Learning) of the Tokugawa Shogunate in Edo, while Takeya was a medical doctor of the Fukuoka Clan. Moreover, Ogata wrote to Mitsukuri in 1858 that he had asked Yukichi Fukuzawa in Edo to buy a Dutch wordbook for him. On the other hand, Genki Kusaka, a student at the Teki-juku, noted in a letter to his parents in 1854 that Ogata had bought Dutch books from Tsuji, official Dutch interpreter of Nagasaki, when the Tsuji stopped by in Osaka on the way to Edo in the February of the year. This paper outlines the above letters to show how Koan Ogata tried to obtain Dutch books from Edo and Nagasaki; their titles and areas are discussed in view of the history of Western learning, and identification is made on the two books that have been left unclarified.

Books↗
PubMed1998

Clinical studies on three cases of the interval form of carbon monoxide poisoning: serial proton magnetic resonance spectroscopy as a prognostic predictor.

Three patients with the interval form of carbon monoxide (CO) poisoning were studied for associations between their clinical courses and serial changes on: (1) MRI; (2) EEG; (3) single photon emission computed tomography with N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP SPECT); and (4) proton magnetic resonance spectroscopy ([1HIMRS) to evaluate their usefulness as prognostic predictors. A hyperintense area on MRI T2-weighted images and a hypointense area on T1-weighted images, appearing in the deep white matter, persisted for a prolonged period even after improvement of the clinical symptoms, and did not become an accurate indicator of clinical evaluation or prognosis. [1H]MRS studies with the volume of interest set in the frontal lobe white matter revealed increases in choline-containing compounds, and reductions of N-acetylaspartate in all cases. These findings normalized in one subclinical case over time. Distinctive findings in the severe cases included increased lactate in two cases showing akinetic mutism, with a difference in prognosis noted according to the degree and period of persistence of this increase. EEG findings were relatively well correlated with clinical symptoms in the early period, with a good correlation no longer consistent after a certain period was exceeded. [123I]IMP SPECT findings did not always reflectclinical symptomatology either. These results indicate that [1H]MRS is the most useful indicator in the clinical evaluation of patients with the interval form of CO poisoning.

Adult↗
PubMed1998

Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3.

Fever, a hallmark of disease, is elicited by exogenous pyrogens, that is, cellular components, such as lipopolysaccharide (LPS), of infectious organisms, as well as by non-infectious inflammatory insults. Both stimulate the production of cytokines, such as interleukin (IL)-1beta, that act on the brain as endogenous pyrogens. Fever can be suppressed by aspirin-like anti-inflammatory drugs. As these drugs share the ability to inhibit prostaglandin biosynthesis, it is thought that a prostaglandin is important in fever generation. Prostaglandin E2 (PGE2) may be a neural mediator of fever, but this has been much debated. PGE2 acts by interacting with four subtypes of PGE receptor, the EP1, EP2, EP3 and EP4 receptors. Here we generate mice lacking each of these receptors by homologous recombination. Only mice lacking the EP3 receptor fail to show a febrile response to PGE2 and to either IL-1beta or LPS. Our results establish that PGE2 mediates fever generation in response to both exogenous and endogenous pyrogens by acting at the EP3 receptor.

Animals↗
PubMed1998

Human genes for KNSL4 and MAZ are located close to one another on chromosome 16p11.2.

KNSL4 (Kid; kinesin-like DNA-binding protein) is a member of the kinesin family that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Myc-associated zinc finger protein (MAZ) participates in both the initiation and the termination of transcription of target genes. We isolated genomic DNA clones that encoded KNSL4 and MAZ from a human cosmid library. Sequence analysis revealed that the two genes were very close to one another. The distance between the two genes was only 1. 2 kb, and this intervening 1.2-kb region was extremely GC-rich. The gene for KNSL4 spanned 16 kb and consisted of 14 exons and 13 introns, while the gene for MAZ spanned 6 kb and consisted of 5 exons and 4 introns. The two genes were mapped to chromosome 16p11.2 by fluorescence in situ hybridization.

Chromosome Mapping↗
PubMed1998

Discovery of IRL 3461: a novel and potent endothelin antagonist with balanced ETA/ETB affinity.

IRL 3461, N-butanesulfonyl-[N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5-+ ++isoxazolyl) -phenyl]-alanyl]-(L)-valineamide, a potent and bifunctional (ETA + ETB) [Ki(ETA) = 1.8 nM, Ki(ETB) = 1.2 nM] antagonist was discovered by structural modification of IRL 2500, an ETB selective antagonist. IRL 3461 was found to be stable on incubation with human, rat, mouse, and guinea pig plasmas.

Animals↗
PubMed1998

Stereoselective synthesis of a novel and bifunctional endothelin antagonist, IRL 3630.

IRL 3630 (3), a single enantiomer of IRL 3461 with more potency was identified. Coupling reaction of the racemic fragment (1) with the chiral (L)-valinesulfonamide (2) under a biphasic solvent system (CH2Cl2-H2O) successfully led to the predominant formation of the desired isomer (3) with concomitant isomerization of 1. IRL 3630, N-butanesulfonyl-[N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5-+ ++isoxazolyl) -phenyl]-(D)-alanyl]-(L)-valineamide, is a highly potent and bifunctional (ETA + ETB) antagonist [Ki(ETA) = 1.5 nM, Ki(ETB) = 1.2 nM].

Animals↗
PubMed1998

Dynamic changes in glucose metabolism by lactate loading as revealed by a positron autoradiography technique using rat living brain slices.

To demonstrate the preference of lactate over glucose as an energy substrate in normal brain tissue under normoxic condition, the dynamic changes in glucose uptake by lactate loading were investigated in living rat brain slices using 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 containing 10 mM glucose at 36 degrees C. During incubation, serial two-dimensional imaging of [18F]FDG uptake in the slices was constructed on the imaging plates. Lactate loading (20 mM) reversibly suppressed the [18F]FDG accumulation up to 80 min. Compared with the pre-loading and the unloaded control values, [18F]FDG uptake was suppressed to 25-45% in cerebral regions and 6-7% in cerebellum. The lactate concentration in the surrounding medium decreased after lactate loading. Hence brain tissue preferentially uses lactate over glucose under normoxic and euglycemic condition.

Animals↗
PubMed1998

Interleukin-13 receptor alpha' but not alpha chain: a functional component of interleukin-4 receptors.

In hematopoietic cells, interleukin-2 receptor (IL-2R) gamma chain (termed gammac) is shown to be a component of the IL-4R system, whereas in nonhematopoietic cells, gammac is absent and it is not a component of the IL-4R system. Here, we show that the IL-13R alpha' chain (termed IL-13Ralpha') but not the IL-13R alpha chain (termed IL-13Ralpha) can substitute for gammac and, thus, IL-13Ralpha' forms a novel component of the IL-4R system. This conclusion was drawn on the basis of chemical cross-linking, immunoprecipitation, the ability of IL-13Ralpha' but not IL-13Ralpha to augment IL-4 binding affinity, and the requirement of IL-13Ralpha' for IL-4-induced STAT6 activation in Chinese hamster ovary (CHO) cells transfected with various receptor subunits. Cotransfection of IL-4 receptor p140 (termed IL-4Rbeta) with gammac or IL-13Ralpha' increased IL-4 binding affinity and allowed for STAT6 activation in response to IL-4. However, cotransfection of all three chains did not further increase IL-4 binding or alter the extent of STAT6 activation suggesting that all three chains together do not seem to participate in IL-4 function. Instead, IL-4Rbeta heterodimerizes with gammac or IL-13Ralpha' and mediates STAT6 activation. Cotransfection of IL-4Rbeta with IL-13Ralpha neither increased IL-4 binding affinity nor allowed for STAT6 activation in response to IL-4 indicating that IL-13Ralpha does not convert binding affinity nor transmit signals for IL-4. Because IL-4 phosphorylates JAK1 and JAK2 tyrosine kinases in nonhematopoietic cells, we investigated whether JAK1 and JAK2 are required for IL-4-induced STAT6 activation in various transfectants. Cotransfection experiments with different chains of IL-4R and kinase-deficient JAK1 and JAK2 mutants in CHO cells showed that JAK1 and JAK2 are required for optimal activation of STAT6 in the alpha' beta transfectant but only partially in the beta gammac transfectant. Taken together, our results show that IL-13Ralpha' is a novel functional component of the IL-4R system and that JAK1 and JAK2 mediate IL-4-induced optimal activation of STAT6 in nonhematopoietic cells.

Animals↗
PubMed1998

A method for motion compensation of a moving nematode Caenorhabditis elegans and its application to frequency analysis of pharyngeal pulsation.

A new sequential image processing method for motion compensation of a moving object with stringy shape has been developed for estimating the pharyngeal pulsation of the nematode Caenorhabditis elegans under several environmental conditions. The method is based on the pixel data transfer on a new image frame while changing the boundary shape and the position but preserving the conformation of the inner structure of an object. All digitized image frames of C. elegans were first converted to motion-compensated images to arrange the pulsation site in the same region of the every transformed frame. The pulsation site was then automatically detected by determining the pixels where the temporal brightness variation was much larger than that of the other pixels. Finally, the pulsation frequency was determined by the Fourier analysis. The validity of our method has been confirmed by analyzing various test data, and the method has been applied for detecting the pharyngeal pulsation frequencies of C. elegans on some environmental conditions, i.e. feed bacteria-free/rich, doping of nerve inactivating ethyl-alcohol and nerve stimulant neurochemical substance of serotonin. The motion compensation method automatically provided reasonable pulsation frequencies which were found to be comparable to those obtained by manual counting. Thus the method is useful for systematic investigations on the variation of pharyngeal pulsation associated with the activity change of the nervous system in environments.

Algorithms↗
PubMed1998

Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4-deficient mice.

The physiological role of the prostaglandin E2 receptor EP4 subtype was investigated by generation of EP4-deficient-mice by gene targeting. Loss of the EP4 receptor was not lethal in utero, but most EP4 (-/-) neonates became pale and lethargic approximately 24 h after birth and died within 72 h. Less than 5% of the EP4 (-/-) mice survived and grew normally more than a year. Histological examination revealed that the ductus arteriosus in dead neonates remained open, while it was partially closed in the survivors. In situ hybridization study showed that EP4 mRNA was strongly expressed in the ductus. These results suggest that neonatal death is at least partly due to patent ductus arteriosus and that the EP4 receptor plays a role in regulation of the patency of this vessel. They also indicate that normal function of the EP4 receptor is essential in neonatal adaptation of the circulatory system.

Animals↗
PubMed1998

X-ray absorption of bromonaphthalene dissolved in supercritical fluid xenon.

The results of Br K-edge X-ray absorption measurements of 1-bromonaphthalene dissolved in supercritical fluid Xe are reported. As the pressure of Xe confined in a high-pressure cell is increased, the absorption spectrum of bromonaphthalene gradually appears, showing that Xe in the supercritical fluid state solvates the bromonaphthalene molecule. The spectrum of the dissolved sample shows a remarkable difference from that of the pure liquid sample in the near-edge region of the X-ray absorption spectrum, reflecting the interaction of the solute material with solvent Xe. Ab initio full multiple-scattering calculations can reproduce the spectral features qualitatively. A large value of the Debye-Waller factor must be introduced to give the best fit, corresponding to a large degree of spatial disorder and violent thermal vibration of the Xe atoms around the Br atom.

Journal Article↗
PubMed1998

Ca2+ administration stimulates the binding of AP-1 factor to the 5'-flanking region of the rat gene for the Ca2+-binding protein regucalcin.

mRNA of the Ca2+-binding protein, regucalcin, is mainly expressed in the liver and only to a small extent in the kidney, and the expression of hepatic regucalcin mRNA is markedly stimulated by Ca2+ administration [Shimokawa and Yamaguchi (1992) FEBS Lett. 305, 151-154]. The existence of nuclear factors that bind to the 5'-flanking region of the rat regucalcin gene was investigated. When nuclear proteins obtained from various rat tissues were used in gel mobility-shift assays, tissue-specific formation of a protein-DNA complex was found in the liver and kidney. An additional novel protein-DNA complex was formed when liver nuclear extracts obtained from Ca2+-administered rats (10mg of Ca2+/100g body weight) were used. Competition gel mobility-shift experiments using consensus and mutant oligonucleotides for AP-1 factor showed that the additional novel complex was formed from binding of the AP-1 factor to the regucalcin gene. Ca2+-induced binding of the AP-1 factor to the regucalcin gene was completely inhibited by simultaneous administration of trifluoperazine, an antagonist of calmodulin, suggesting that the activation of nuclear AP-1 protein is partly mediated through a Ca2+/calmodulin-dependent pathway. Moreover, the 5'-flanking region of the rat regucalcin gene ligated to a luciferase reporter gene possessed the promoter activity in H4-II-E hepatoma cells. This promoter activity was enhanced by treatment with Bay K 8644, a Ca2+-channel agonist. The present study demonstrates that the Ca2+-response sequences are located within the 5'-flanking region of the rat regucalcin gene.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Advanced glycation end products in age-related macular degeneration.

OBJECTIVE: To investigate the localization of N epsilon-(carboxymethyl)lysine (CML), a component and major immunologic epitope of advanced glycation end products, in aged eyes and choroidal neovascular membranes (CNVMs) surgically excised from eyes with age-related macular degeneration. METHODS: Immunohistochemistry for CML was performed using 8 snap-frozen, surgically excised CNVMs. Twelve eyes from patients aged 69 to 82 years and 2 donor eyes, 1 each from a 23-week-old fetus and 21-year-old patient, without age-related macular degeneration or diabetic retinopathy were also examined. To determine if retinal pigment epithelial cells in CNVMs accumulate advanced glycation end products, cytokeratin and CML were stained in paired serial sections. RESULTS: Soft, macular drusen and/or basal laminar and basal linear deposits were observed in 8 of 12 aged eyes. Each case showed CML accumulation, while overlying retinal pigment epithelial cells showed no accumulation in all 12 eyes. In CNVMs, however, retinal pigment epithelial cells showed CML accumulation in their cytoplasm. CONCLUSION: The additional accumulation of advanced glycation end products in soft, macular drusen and/or retinal pigment epithelial cells may play a role in the pathogenesis of CNVM formation in age-related macular degeneration. CLINICAL RELEVANCE: Recently, advanced glycation end products have been found to play a role both in aging changes and neovascularization. Localization of advanced glycation end products in the above-mentioned tissue may lead to a better understanding of the pathogenesis of age-related macular degeneration.

Adult↗
PubMed1998

Verapamil inhibits proliferation, migration and protein kinase C activity in human retinal pigment epithelial cells.

The effects of three calcium channel blockers, verapamil, diltiazem and nifedipine, were examined on in vitro proliferation and migration of human retinal pigment epithelial cells. Human retinal pigment epithelial cells were seeded in Dulbecco's modified essential medium with 10% fetal bovine serum and different concentrations of the three calcium channel blockers. After 3 days of treatment, cell proliferation was determined by cell counting and by [3H]-thymidine uptake. Cell viability was determined with trypan blue exclusion. For determination of cell migration, retinal pigment epithelial cells were grown to confluence and then growth-inhibited with mitomycin C. After a 3 mm zone was denuded, the cells were treated with different concentrations of the calcium channel antagonists. After 24 hr, the cells that had migrated over the wound edge were counted. To determine the involvement of protein kinase C in the verapamil effect, its activity was measured in both verapamil-treated and untreated cells. Verapamil dose dependently inhibited serum-induced proliferation of retinal pigment epithelial cells, when measured by cell number (IC50 14.6 microM) or [3H]-thymidine incorporation (IC50 11.3 microM). At concentrations of 15 microM and below, there was no effect on cell viability, as determined by morphology and trypan blue exclusion. Diltiazem inhibited cell proliferation at a concentration of 100 microM; however, 100 microM nifedipine had no effect. Verapamil showed a significant inhibition of serum-induced migration in the range of 10 microM to 0.1 microM. The IC50 of the inhibition of retinal pigment epithelial cell proliferation and migration by verapamil is significantly higher than that seen for effects on calcium channel blockage. Eight micromolar verapamil reversibly inhibited total protein kinase-C activity in retinal pigment epithelial cells suggesting the possibility that the drug may act by inhibiting the protein kinase-C pathway. These data suggest the potential of the calcium channel blocker verapamil as a pharmacological modulator of disorders such as proliferative vitreoretinopathy in which there is increased retinal pigment epithelial cell proliferation and migration.

Calcium Channel Blockers↗
PubMed1998

Expression and characterization of deletion recombinants of two cGMP-inhibited cyclic nucleotide phosphodiesterases (PDE-3).

cDNAs encoding two PDE-3 or cyclic GMP-inhibited (cGI) cyclic nucleotide phosphodiesterase (PDE) isoforms, RPDE-3B (RcGIP1) and HPDE-3A (HcGIP2), were cloned from rat (R) adipose tissue and human (H) heart cDNA libraries. Deletion and N- and C-terminal truncation mutants were expressed in Escherichia coli in order to define their catalytic core. Active mutants of both RPDE-3B and HPDE-3A included the domain conserved among all PDEs plus additional upstream and downstream sequences. An RPDE-3B mutant consisting of the conserved domain alone and one from which the RPDE-3B 44-amino acid insertion was deleted exhibited little or no activity. All active recombinants exhibited a high affinity (< 1 microM) for cyclic AMP (cAMP) and cyclic GMP (cGMP), were inhibited by cAMP, cGMP, and cilostamide, but not by rolipram, and were photolabeled with [32P]-cGMP. The IC50 values for cGMP inhibition of cAMP hydrolysis were lower for HPDE-3A than for RPDE-3B recombinants. The deduced amino acid sequences of HPDE-3A and RPDE-3B catalytic domains are very similar except for the 44-amino acid insertion not found in other PDEs. It is possible that this insertion may not only distinguish PDE-3 catalytic domains from other PDEs and identify catalytic domains of PDE-3 subfamilies or conserved members of the PDE-3 gene family, but may also be involved in the regulation of sensitivity of PDE-3s to cGMP.

3',5'-Cyclic-AMP Phosphodiesterases↗