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Biomedical subjects

K Haga

Publications and source records attributed to K Haga.

At least 37 records · Page 2Linked to original sources

Reconstruction for the brilliance-upgrading project of the Photon Factory storage ring.

Reconstruction of the Photon Factory storage ring (PF ring; 2.5 GeV) is now in progress to provide very brilliant synchrotron radiation to users, i.e. the emittance is being reduced by a factor of five. Components, such as the quadrupole and sextupole magnets, vacuum chambers, beamlines and beam-position monitors, are being replaced by new ones in 16 normal-cell sections of the PF ring. The accelerating cavities, injection systems and control systems are also being replaced. Operation will commence when the improvements are completed on 1 October 1997.

Journal Article↗

New beam-position monitor system for upgraded Photon Factory storage ring.

Accompanying the brilliance-upgrading project at the Photon Factory storage ring, the beam-position monitor (BPM) system has been renovated. The new system was designed to enable precise and fast measurements to correct the closed-orbit distortion (COD), as well as to feed back the orbit position during user runs. There are 42 BPMs newly installed, amounting to a total of 65 BPMs. All of the BPMs are calibrated on the test bench using a coaxially strung metallic wire. The measured electrical offsets are typically 200 micro m in both directions, which is 1/2-1/3 of those of the old-type BPMs. In the signal-processing system, PIN diode switches are employed in order to improve reliability. In the fastest mode, this system is capable of measuring COD within about 10 ms; this fast acquisition will allow fast suppression of the beam movement for frequencies up to 50 Hz using a global feedback system.

Journal Article↗

Fabrication and characterization of multilayer supermirrors for hard X-ray optics.

Multilayer supermirrors stacked with three sets of Pt/C combinations have been fabricated on a flat float-glass and conical replica foil mirror using a magnetron DC sputtering system, and applied to X-ray optical systems in the hard X-ray region. The design of the supermirror is optimized to obtain the highest integrated reflectivity in the energy band and at the grazing angle concerned. X-ray reflectivities of 30% in the 25-35 keV band at an incidence angle of 0.3 degrees were obtained.

Journal Article↗

Characterization of substrates for use in X-ray multilayer optics.

The optical performance of platinum-carbon multilayers deposited onto different substrates has been examined. Specular reflectivity and non-specular diffuse scattering were measured to study the replication of substrate roughness into the multilayer structure. Surface topography was measured before and after deposition using a scanning probe microscope and a mechanical profiler.

Journal Article↗

Auxin-growth relationships in maize coleoptiles and pea internodes and control by auxin of the tissue sensitivity to auxin

Growth of a zone of maize (Zea mays L.) coleoptiles and pea (Pisum sativum L.) internodes was greatly suppressed when the organ was decapitated or ringed at an upper position with the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) mixed with lanolin. The transport of apically applied 3H-labeled indole-3-acetic acid (IAA) was similarly inhibited by NPA. The growth suppressed by NPA or decapitation was restored by the IAA mixed with lanolin and applied directly to the zone, and the maximal capacity to respond to IAA did not change after NPA treatment, although it declined slightly after decapitation. The growth rate at IAA saturation was greater than the rate in intact, nontreated plants. It was concluded that growth is limited and controlled by auxin supplied from the apical region. In maize coleoptiles the sensitivity to IAA increased more than 3 times when the auxin level was reduced over a few hours with NPA treatment. This result, together with our previous result that the maximal capacity to respond to IAA declines in pea internodes when the IAA level is enhanced for a few hours, indicates that the IAA concentration-response relationship is subject to relatively slow adaptive regulation by IAA itself. The spontaneous growth recovery observed in decapitated maize coleoptiles was prevented by an NPA ring placed at an upper position of the stump, supporting the view that recovery is due to regenerated auxin-producing activity. The sensitivity increase also appeared to participate in an early recovery phase, causing a growth rate greater than in intact plants.

Journal Article↗

The complete genome sequence of the gram-positive bacterium Bacillus subtilis.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

Bacillus subtilis↗

Sequence analysis of a 25-kb segment in the 17 degrees-19 degrees region of the Bacillus subtilis chromosome containing ada locus.

As a part of the Bacillus subtilis genome sequencing project, we have determined a 25-kb sequence covering the 17 degrees-19 degrees region. This region contains 26 complete open reading frames (ORFs) including the alkA and adaA/B operon, which encode genes for adaptive response to DNA alkylation. A homology search for the newly identified 21 ORFs revealed that 4 of them exhibit a significant similarity to known proteins, e.g., methicillin-resistant Staphylococcus aureus (MRSA) protein homolog, proteins involved in chloramphenicol resistance, glucosamine synthase and an ABC transporter protein. The remaining 17 ORFs did not show any significant sequence similarities to known gene products in the database.

Bacillus subtilis↗

Sequence analysis of a 45-kb segment in the 19 degrees-23 degrees region of the Bacillus subtilis chromosome containing glpT and mpr loci.

The nucleotide sequence of a 45,137-bp segment covering the 19 degrees and 23 degrees region in the 360 degrees map of the Bacillus subtilis genome was determined. This region contained 45 open reading frames (ORFs) including 7 which corresponded to the products of genes with known functions that had been previously sequenced. The known genes were: glpT and glpQ for glycerol utilization pathway; purT for a part of the purine synthesis pathway; mpr for an extracellular metalloprotease; pss and psd for the parts of the phospholipid synthesis pathway; and gltP for a glutamine transporter. Deduced amino acid sequences of the 22 newly identified ORFs showed significant homologies to known gene products in the database such as a Methicillin-resistant Staphylococcus aureus (MRSA) gene which is related to drug resistance, a two-component response regulator, a series of amino acid permeases, transcriptional regulators, beta-lactamase, the phosphotransferase system (PTS) enzyme II for sugar uptake, and the eukaryotic ECA39 gene which is associated with cancer and apoptosis, etc. The remaining 16 ORFs did not show any significant sequence similarities to known gene products in the database.

Animals↗

Ca2+-dependent inhibition of G protein-coupled receptor kinase 2 by calmodulin.

Agonist- or light-dependent phosphorylation of muscarinic acetylcholine receptor m2 subtypes (m2 receptors) or rhodopsin by G protein-coupled receptor kinase 2 (GRK2) was found to be inhibited by calmodulin in a Ca2+-dependent manner. The phosphorylation was fully inhibited in the absence of G protein betagamma subunits and partially inhibited in the presence of betagamma subunits. The dose-response curve for stimulation by betagamma subunits of the m2 and rhodopsin phosphorylation was shifted to the higher concentration of betagamma subunits by addition of Ca2+-calmodulin. The phosphorylation by GRK2 of a glutathione S-transferase fusion protein containing a peptide corresponding to the central part of the third intracellular loop of m2 receptors (I3-GST) was not affected by Ca2+-calmodulin in the presence or absence of betagamma subunits, but the agonist-dependent stimulation of I3-GST phosphorylation by an I3-deleted m2 receptor mutant in the presence of betagamma subunits was suppressed by Ca2+-calmodulin. These results indicate that Ca2+-calmodulin does not directly interact with the catalytic site of GRK2 but inhibits the kinase activity of GRK2 by interfering with the activation of GRK2 by agonist-bound m2 receptors and G protein betagamma subunits. In agreement with the assumption that GRK2 activity is suppressed by the increase in intracellular Ca2+, the sequestration of m2 receptors expressed in Chinese hamster ovary cells was found to be attenuated by the treatment with a Ca2+ ionophore, A23187.

Animals↗

High affinity binding of azasetron hydrochloride to 5-hydroxytryptamine3 receptors in the small intestine of rats.

The binding affinity of azasetron hydrochloride (azasetron) for the 5-hydroxytryptamine3 (5-HT3) receptor in a tissue preparation of rat small intestine was investigated by using [3H]granisetron as a radioligand. Scatchard analysis of specific [3H]granisetron binding revealed a single population of saturable binding sites in the tissue preparation. At this site, azasetron was concentration-dependently competitive with [3H]granisetron, and it inhibited the specific [3H]granisetron binding with a Ki value of 0.33 nM. Azasetron has a high affinity for 5-HT3 receptor in the gastrointestinal organ, the very site of its antiemetic action against chemotherapy-induced emesis.

Animals↗

X-ray structure of cyclodextrin glucanotransferase from alkalophilic Bacillus sp. 1011. Comparison of two independent molecules at 1.8 A resolution.

Cyclodextrin glucanotransferase (CGTase) is an enzyme which produces cyclodextrins by the degradation of starch. The enzyme from alkalophilic Bacillus sp. 1011, consisting of 686 amino acid residues, was crystallized from the solution containing 20% PEG 3000 and 20% 2-propanol at pH 5.6 adjusted with citrate buffer. The space group was P1 and the unit cell contained two molecules (V(m) = 2.41 A(3) Da(-1)). The structure was solved by the molecular replacement method and refined to a conventional R value of 0.161 (R(free) = 0.211) for the reflections in the resolution range 1.8-10 A by energy minimization combined with simulated annealing. The molecule consists of five domains, designated A-E, and its backbone structure is similar to the structure of other bacterial CGTases. The molecule has two calcium binding sites where calcium ions are coordinated by seven ligands, forming a distorted pentagonal bipyramid. The two independent molecules are related by a pseudotwofold symmetry and are superimposed with an r.m.s. deviation value of 0.32 A for equivalent C(alpha) atoms. Comparison of these molecules indicated the relatively large mobility of domains C and E with respect to domain A. The active site is filled with water molecules forming a hydrogen-bond network with polar side-chain groups. Two water molecules commonly found in the active center of both molecules link to several catalytically important residues by hydrogen bonds and participate in maintaining a similar orientation of side chains in the two independent molecules.

Journal Article↗

Calcium-bound recoverin targets rhodopsin kinase to membranes to inhibit rhodopsin phosphorylation.

In rod photoreceptor cells, Ca2+-bound recoverin associates with disk membranes and inhibits light-dependent phosphorylation of rhodopsin. However, the functional significance of Ca2+-induced membrane association of recoverin has not been fully evaluated. We found that Ca2+-bound recoverin forms a complex with rhodopsin kinase preferentially at the membrane surface. Addition of increasing amounts of membranes promoted the membrane association of recoverin, and remarkably suppressed rhodopsin kinase activity. It was concluded that the Ca2+-recoverin-rhodopsin kinase complex is stabilized by membrane association, leading to effective suppression of the kinase activity.

Animals↗

Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C.

Human muscarinic acetylcholine receptor m1 subtypes (m1 receptors) were expressed in and purified from insect Sf9 cells and then subjected to phosphorylation by G protein-coupled receptor kinase 2 (GRK2) expressed in and purified from Sf9 cells and by protein kinase C purified from rat brain (a mixture of alpha, beta, and gamma types, PKC). The m1 receptor was phosphorylated by either GRK2 or PKC in an agonist-dependent or independent manner, respectively. G protein beta gamma subunits stimulated the phosphorylation by GRK2 but did not affect the phosphorylation by PKC. The number of incorporated phosphates was 4.6 and 2.8 mol/mol of receptor for phoshorylation by GRK2 and PKC, respectively. The number of incorporated phosphates was 7.5 mol/mol receptor for phosphorylation by GRK2 followed by PKC, but was 5.8 mol/mol of receptor for the phosphorylation by PKC followed by GRK2. Major sites phosphorylated by GRK2 and PKC were located in the third intracellular loop and the carboxyl-terminal tail, respectively. These results indicate that GRK2 and PKC phosphorylate different sites of m1 receptors and that the phosphorylation by PKC partially inhibits the phosphorylation by GRK2, probably by affecting activation of GRK2 by agonist-bound receptors.

Amino Acid Sequence↗

[The affinities of mosapramine for the dopamine receptor subtypes in human cell lines expressing D2, D3 and D4 receptors].

The affinities of mosapramine hydrochloride, an iminodibenzyl antipsychotic drug, for dopamine receptor subtypes were determined by human dopamine D2, D3 and D4 receptors expressed in several cell lines and compared with those of other neuroleptics. Tritiated spiperone bound to the membrane of transfected cells in a saturable manner, and the Kd values for dopamine D2, D3 and D4 receptors were 0.021, 0.12 and 0.10 nM, respectively. Mosapramine showed the highest affinities for these receptor subtypes among the antipsychotics tested. The ratio of Ki values between D2 and D3 (D2 Ki/D3 Ki ratio) in mosapramine was higher than that of haloperidol, indicating that the effects of mosapramine on D3 receptors were more potent than those of haloperidol. On the other hand, clozapine, risperidone and raclopride had higher affinity to D4, D2 and D3 subtypes, respectively. The affinities of mosapramine for D4 receptors was 8 times higher than that of clozapine, and the affinity for D3 receptors was 40 times higher than that of raclopride. These results suggest that the effect on D3 receptors may underlie at least a portion of mosapramine's atypical clinical profile.

Antipsychotic Agents↗

[Preliminary study of radiological image transmission with B-ISDN].

We evaluated the utility of image transmission using broad band ISDN (B-ISDN). The B-ISDN network links Tohoku University Hospital (TUH), interfaced with CDDI, and Tohoku University Department of Technology, interfaced with FDDI (including Tohoku University Computer Center interfaced with Ethernet), at 10km distance interfaced to a Unix workstation. Voluminous radiographic images like MRI 3-D images of the pelvic organs digitized at 5-20 megabytes were transmitted at mean data rates of 1.03Mbps (CDDI-Ethernet) and 30.1Mbps (FDDI-CDDI) with no image distortion. Initially the image data are transmitted to the Computer Center & Department of Technology, then processed and relayed to TUH. B-ISDN can provide fast, accurate image transmission.

Computer Communication Networks↗