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Biomedical subjects

T Nagao

Publications and source records attributed to T Nagao.

At least 37 records · Page 2Linked to original sources

Origin of the stability of Ge(105) on si: a new structure model and surface strain relaxation.

The structure of Ge(105)-(1 x 2) grown on Si(105) is examined by scanning tunneling microscopy (STM) and first-principles calculations. The morphology evolution with an increasing amount of Ge deposited documents the existence of a tensile surface strain in Si(105) and its relaxation with increasing coverage of Ge. A detailed analysis of high-resolution STM images and first-principles calculations produce a new stable model for the Ge(105)-(1 x 2) structure formed on the Si(105) surface that includes the existence of surface strain. It corrects the model developed from early observations of the facets of "hut" clusters grown on Si(001).

Journal Article↗

Brain tyramine and reproductive states of workers in honeybees.

To explore the role of tyramine in the transformation of reproductive states of honeybee workers, brain levels of tyramine and N-acetyltyramine were measured in both normal and queenless workers. Queenless workers had higher tyramine levels and lower N-acetyltyramine levels than normal workers did. Intermediate reproductive workers that were transferred into a normal colony from a queenless colony had intermediate levels of tyramine and N-acetyltyramine. Elevation of tyramine in the queenless workers occurred at an earlier adult stage than elevation of dopamine. Tyramine levels in intermediate reproductive workers returned to the levels seen in normal workers, but dopamine levels in intermediate reproductive workers remained elevated at the same level as in queenless workers. Thus, brain tyramine may be regulated by the colony condition with or without a queen. Injection of an amine uptake inhibitor, reserpine, depleted tyramine and elevated N-acetyltyramine. Distributions of tyramine and dopamine within the brain were distinctively different, whereas distributions of N-acetyltyramine and N-acetyldopamine were similar, suggesting that each functional amine is stored in specific neurosecretory cells and released to the relevant receptor sites but that metabolism into each N-acetylmetabolite is determined by diffusion.

Journal Article↗

Epithelial cell proliferation in oral lichen planus.

Although the pathogenesis of oral lichen planus (OLP) is not clear, a small proportion of cases with OLP are reported to transform to cancer. We examined the epithelial cell proliferation status of OLP to relate the labelling index to microscopic features surveyed routinely in pathology. Mucosal biopsies obtained from 44 cases diagnosed with OLP with an intact oral epithelium and 10 normal control specimens from Japanese subjects were immunohistochemically stained with MIB and p53 antibodies. The Ki67 labelling index (LI) was significantly higher in OLP compared with normal controls. A particularly large number of OLP lesions (64%) were p53 positive. No association was, however, found with p53 expression and the Ki67 LI. Atrophic and flat epithelia had a quantitatively higher LI, which did not significantly differ from acanthotic biopsies. Increased cell proliferation in OLP is likely to be a secondary phenomenon due to the damage inflicted on keratinocytes by infiltrating mononuclear cells in the submucosa.

Adult↗

Chronic dental infections mimicking temporomandibular disorders.

BACKGROUND: Trismus and jaw pain are not only caused by temporomandibular disorders (TMD), but also by various pathologies, namely infection, trauma, or neoplasms. TMD-like symptoms, as a result of the pathologies, may be confusing to a clinician. This paper reports two cases of chronic dental infection mimicking TMD. METHODS: Two patients were initially diagnosed with, and treated for, TMD. However the patients did not respond to the treatment. Limited range of motion and jaw pain were then clinically evaluated for differential diagnoses. Laboratory examinations and computerized tomography (CT) scans were carried out to disclose any underlying lesion. RESULTS: Laboratory examination, such as, C-reactive protein helped to detect latent infection. CT scans revealed insidious chronic dental infection imitating TMD. Surgical drainage and chemotherapy resolved the symptoms. CONCLUSION: The importance of a rational diagnostic process, including clinical and laboratory examinations and radiologic imaging, cannot be over-emphasized in elucidating true cause of the symptoms.

Aged↗

Novel peptides from assassin bugs (Hemiptera: Reduviidae): isolation, chemical and biological characterization.

Three novel peptides were isolated from the venomous saliva of predatory reduviids. They were identified by mass spectrometry and HPLC analysis and consist of 34-36 amino acid residues. They are relatively homologous to the calcium channel blockers omega-conotoxins from marine cone snails and belong to the four-loop Cys scaffold structural class. Ptu1, the shortest peptide, was chemically synthesized (sPtu1) and co-eluted with its native form. Circular dichroism spectra of the sPtu1 showed a high content of beta-turns similar to that of omega-conotoxins GVIA and MVIIA. Electrophysiological experiments demonstrated that sPtu1 reversibly blocks the N-type calcium channels expressed in BHK cells.

Amino Acid Sequence↗

Dispersion and damping of a two-dimensional plasmon in a metallic surface-state band.

We have studied, for the first time, the energy and the linewidth dispersion of a plasmon in a dense two-dimensional electron system in a metallic surface-state band on a silicon surface. As expected from the considerably high effective density and long Fermi wavelength of the system, the plasmon energy dispersion exhibited an excellent agreement with the nearly free-electron theory. However, in a small wave number region below the Landau edge, we have observed an anomalous linewidth dispersion which nearly free-electron theories do not predict.

Journal Article↗

Clathrin box in G protein-coupled receptor kinase 2.

beta(1)-Adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. However, beta(1)AR can internalize as G protein-coupled receptor kinase 2 (GRK2) is fused to its carboxyl terminus. Internalization of the beta(1)AR and GRK2 fusion protein (beta(1)AR/GRK2) is dependent on dynamin but independent of beta-arrestin and phosphorylation. The beta(1)AR/GRK2 fusion protein internalizes via clathrin-coated pits and is found to co-localize with the endosome that contains transferrin. The fusion proteins consisting of beta(1)AR and various portions of GRK2 reveal that the residues 498-502 in the carboxyl-terminal domain of GRK2 are critical to promote internalization of the fusion proteins. This domain contains a consensus sequence of a clathrin-binding motif defined as a clathrin box. In vitro binding assays show that the residues 498-502 of GRK2 bind the amino-terminal domain of clathrin heavy chain to almost the same extent as beta-arrestin1. The mutation of the clathrin box in the carboxyl-terminal domain of GRK2 results in the loss of the ability to promote internalization of the fusion protein. GRK2 activity increases and then decreases as the concentration of clathrin heavy chain increases. Taken together, these results imply that GRK2 contains a functional clathrin box and directly interacts with clathrin to modulate its function.

Amino Acid Sequence↗

Reconstitution of acid secretion in digitonin-permeabilized rabbit gastric glands. Identification of cytosolic regulatory factors.

When isolated rabbit gastric glands were permeabilized with digitonin, they lost their ability to secrete acid, as monitored by [14C]aminopyrine accumulation, and they never recovered by supplement with cytosol prepared from gastric mucosa. However, the permeabilized glands elicited acid secretion when brain cytosol was supplemented. Fractionation of gastric cytosol by gel filtration revealed that the fraction at 30 kDa stimulated permeabilized glands by itself, whereas the 200-kDa fraction potently inhibited brain cytosol-stimulated acid secretion. Brain cytosol contained only the former stimulatory factor. With further gel filtration, the 30-kDa activator was separated into two components, 20 kDa (peak 1) and 1.8 kDa (peak 2), both of which are necessary for full activity. We purified peak 1 from bovine brain, and phosphatidylinositol transfer protein (PITP) was identified as the main component of the activity. The stimulating activity in brain and gastric mucosa correlated with the contents of PITP, and recombinant PITP mimicked the effect of peak 1, suggesting that PITP is one of the essential components in gastric acid secretion. When gastric glands were stimulated, the inhibitory activity, but not stimulatory activity, in the cytosol was increased. This suggests a regulatory mechanism such as stimulation translocates the inhibitory component from the secretory site on the membrane to cytosol. These results demonstrate a high degree of usefulness for our present model, the reconstituted digitonin-permeabilized gastric glands.

Animals↗

Low affinity of beta1-adrenergic receptor for beta-arrestins explains the resistance to agonist-induced internalization.

It has been reported that beta-arrestin is essential for the internalization of many G protein-coupled receptors. Since beta1-adrenergic receptor (beta1AR) shows the resistance to agonist-induced internalization, we examine the interaction of beta-arrestin with beta1AR with three different approaches: translocation of beta-arrestin to the plasma membrane, direct binding of in vitro translated beta-arrestin to intracellular domains of beta1- and beta2ARs, inhibition of beta1- and beta2AR-stimulated adenylyl cyclase activities by beta-arrestin. The enhanced green fluorescent protein (EGFP)-tagged beta-arrestin 2 (beta-arrestin 2-GFP) translocates to and stays at the plasma membrane by beta2AR stimulation. Beta-arrestin 2-GFP also translocates to the plasma membrane upon beta1AR stimulation. However, it returns to the cytoplasm 10 - 30 min after agonist stimulation. The amount of beta-arrestin bound to the third intracellular loop and the carboxyl tail of beta1AR is lower than that of beta2AR. The fusion protein of beta-arrestin 1 with glutathione-S-transferase inhibits the beta1- and beta2AR-stimulated adenylyl cyclase activities. However, inhibition of the beta1AR-stimulated activity requires a higher amount of the fusion protein than that of the beta2AR-stimulated activity. These results suggest that affinity of beta1AR for beta-arrestins is lower than that of beta2AR, and explains the resistance to agonist-induced internalization. This conclusion is further supported by the finding that beta-arrestin can induce internalization of beta1AR when beta-arrestin 1 fused to the carboxyl tail of beta1AR.

Adenylyl Cyclase Inhibitors↗

Thromboxane A(2) causes retarded clearance of aggregated protein in glomeruli of nephritic mice.

Recently, it has been demonstrated that the production of prostaglandins and thromboxane is increased in patients with chronic glomerulonephritis and lupus nephritis. We recently demonstrated that thromboxane A(2) delayed the clearance of heat-aggregated bovine serum albumin deposited in glomeruli. In the present study, we investigated the effect of thromboxane A(2) on the clearance of macromolecules in nephritic glomeruli. First, we attempted to clarify the conditions for the clearance of heat-aggregated bovine serum albumin in nephritic glomeruli, using glomeruli isolated from control and anti-glomerular basement membrane nephritic mice. Heat-aggregated bovine serum albumin was injected twice into each mouse. The glomeruli were then isolated and incubated in culture medium. The heat-aggregated bovine serum albumin content of control glomeruli gradually diminished with incubation time up to 24 h. The heat-aggregated bovine serum albumin content of nephritic glomeruli was 69% higher than that of control glomeruli at 24 h incubation. The production of thromboxane B(2) (the stable metabolite of thromboxane A(2)) in nephritic glomeruli showed about a sevenfold increase compared with control. DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid hydrochloride], a thromboxane A(2) synthase inhibitor, and KT2-962 [sodium 3-(4-(4-chlorophenyl-butylsulfonamido) butyl)-6-isopropylazulene-1-sulfonate], a selective thromboxane A(2) receptor antagonist, significantly reduced the heat-aggregated bovine serum albumin content in nephritic glomeruli. Normal glomeruli treated with U-46619 [15S-hydroxy-11a,9a-(epoxymethano)prosta-5Z,13E-dienoic acid], a stable analogue of thromboxane A(2), had significantly more heat-aggregated bovine serum albumin than control glomeruli. We next investigated whether thromboxane A(2) could affect the uptake/disposal of heat-aggregated bovine serum albumin by cultured rat mesangial cells. U-46619 significantly enhanced the uptake and inhibited the disposal of heat-aggregated bovine serum albumin by mesangial cells. Finally, we performed experiments to elucidate the role of the thromboxane A(2) receptor (TP receptor) in the clearance of heat-aggregated bovine serum albumin using TP-deficient mice. The glomerular heat-aggregated bovine serum albumin content of TP-receptor knockout [TP(-/-)] mice was lower than that of wild-type [WT(+/+)] mice. U-46619 dose dependently increased the uptake of heat-aggregated bovine serum albumin by mesangial cells in WT(+/+) mice, but not in the TP(-/-) mice. These findings suggest that thromboxane A(2) retards the clearance of aggregated protein in nephritic glomeruli and may contribute to the pathophysiology of glomerulonephritis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Diastereoselective tandem Michael-intramolecular Wittig reactions of a cyclic phosphonium ylide with 8-phenylmenthyl enoates.

The diastereoselective tandem Michael-intramolecular Wittig reactions of a five-membered cyclic phosphonium ylide 2 using 8-phenylmenthyl enoates were examined. The reaction of the phosphonium ylide with 8-phenylmenthyl cinnamate followed by the hydrolysis of the resulting enol ether 4a afforded (3R,4S)-4-(diphenylphosphinyl)-3-phenylcycloheptanone (3R,4S)-5a as the major isomer. The diastereoselectivity of the initial tandem reactions was estimated to be 94:6 from the 31P NMR of a mixture of the diastereomeric ketal derivatives 6a and 6'a which were obtained by the reaction of 5a with (2R,3R)-2,3-butanediol, and the absolute configuration of the major isomer was determined by the single-crystal X-ray analysis. Similar reactions using some 8-phenylmenthyl alkenoates were attempted. As a result, it was clarified that the corresponding trans-ketones 5b-d were obtained and that the diastereomer ratios of their ketal derivatives were 60:40-73:27.

Journal Article↗

Ser(1901) of alpha(1C) subunit is required for the PKA-mediated enhancement of L-type Ca(2+) channel currents but not for the negative shift of activation.

Cardiac L-type Ca(2+) channel is facilitated by protein kinase A (PKA)-mediated phosphorylation. Here, we investigated the role of Ser(1901), a putative phosphorylation site in the carboxy-terminal of rat brain type-II alpha(1C) subunit (rbCII), in the PKA-mediated regulation. Forskolin (3 microM) enhanced Ca(2+) channel currents (I(Ca)) and shifted the activation curve to negative voltages, which were abolished by protein kinase inhibitor. Replacement of Ser(1901) of rbCII by Ala abolished the enhancement of I(Ca) by forskolin but not the shift of the activation curve. These results indicate that Ser(1901) is required for the PKA-mediated enhancement of I(Ca), and that the voltage-dependence of the activation of I(Ca) appears to be modulated via another PKA phosphorylation site.

Amino Acid Sequence↗

3,28-Di-O-(dimethylsuccinyl)-betulin isomers as anti-HIV agents.

Four isomers of 3,28-di-O-(dimethylsuccinyl)-betulin were prepared and evaluated for anti-HIV activity against HIV-1 replication in H9 lymphocyte cells. 3-O-(3',3'-Dimethylsuccinyl)-28-O-(2", 2"-dimethvlsuccinyl)-betulin (11) was the most potent anti-HIV compound with an EC5, value of 0.00087 microM and a TI value of 42,400.

Anti-HIV Agents↗