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K Namba

Publications and source records attributed to K Namba.

At least 19 recordsLinked to original sources
PubMed2006

Alpha-MSH regulates protein ubiquitination in T cells.

The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) suppresses IFN-gamma + T cells from mice. We discovered, however, that despite this significant production by DTH-mediating effector CD4 supression of IFN-gamma production, alpha-MSH-treated effector T cells had the same level of IFN-gamma mRNA expression and intracellular IFN-gamma protein as untreated activated T cells. In order to explain why IFN-gamma production was suppressed in the face of unchanged mRNA and intracellular IFN-gamma levels, we looked for mechanisms that could increase the degradation of IFN-gamma within the alpha-MSH-treated T cells. Among the known pathways of post-translational intracellular protein modification, the ubiquitin-proteosome system was examined in alpha-MSH-treated T cells to see if a post-translational protein modification occurred to prevent IFN-gamma secretion from the cell. Immunoblots from alpha-MSH-treated T cells showed higher levels of protein ubiquitination when compared to untreated T cells. Resting T cells treated with alpha-MSH also demonstrated enhanced protein ubiquitination. We found that IFN-gamma is one of the ubiquitinated proteins in the alpha-MSH-treated activated T cells. Our results demonstrate that one of the mechanisms by which alpha-MSH regulates T cell activity is through mediating a change in the pattern of protein ubiquitination in T cells.

Animals↗
PubMed2006

The utility of DynaCT in neuroendovascular procedures.

The authors present 3 patients who underwent neuroendovascular procedures in which DynaCT produced by a flat-panel detector facilitated management of complications. As part of a combined CT/angiography suite, DynaCT offered the major advantage of immediate detection or exclusion of intracranial complication without patient transfer. The quality of cone-volume CT-generated images produced by DynaCT was sufficient to make a diagnosis.

Adult↗
PubMed2006

Treatment of cerebral aneurysms with hydrogel-coated platinum coils (HydroCoil): early single-center experience.

PURPOSE: The authors report their experience using HydroCoils in the treatment of cerebral aneurysms. METHODS: We performed a retrospective review of the first 100 nonrandomized patients (104 coiled saccular cerebral aneurysms) treated with HydroCoils during a 27-month period. RESULTS: The average percentage of HydroCoil by length detached in treated aneurysms was 45.5% (range, 9.9-100%). Immediate postprocedure angiography demonstrated complete aneurysm occlusion in 34%, neck remnant in 35%, and incomplete occlusion in 32%. Immediate procedure-related morbidity and mortality rates were 5.8% and 0%, respectively. Angiographic follow-up was obtained in 51% (51/100 patients; 53/104 aneurysms; average, 10.3 months; range, 0-31 months). In these 53 angiographically followed aneurysms, the overall recanalization rate was 21%: no recanalization occurred in 23 aneurysms with small size (<10 mm)/small neck (<4 mm) (S/S); 4 recanalizations occurred in 7 aneurysms with small size/wide neck (>4 mm) (S/W); 6 recanalizations (27%) occurred in 22 large (L) aneurysms (>10-25 mm, 70% angiographic follow-up); and 1 giant (G) (>25 mm) aneurysm recanalized. A large proportion of aneurysms that were not initially completely occluded were completely occluded on follow-up (15/43 [35%]). Clinical follow-up was obtained in 73 patients (73%; average, 5.3 months; range, 0-24 months): 93% of these patients were neurologically improved or unchanged. Three patients rehemorrhaged and 3 patients with unruptured aneurysms developed delayed hydrocephalus. CONCLUSIONS: The overall safety profile of HydroCoils appears acceptable. Preliminary midterm observations suggest less coil compaction/aneurysm recanalization in large aneurysms. However, HydroCoil-related delayed hydrocephalus is a concern.

Adolescent↗
PubMed2005

Decrease in the glyceraldehyde derived advanced glycation end products in the sera of patients with Vogt-Koyanagi-Harada disease.

BACKGROUND/AIMS: Advanced glycation end products (AGEs) are considered to act as mediators of both age related pathologies and diabetic complications. It was recently reported that glyceraldehyde derived AGE (AGE-2) has a strong biological effect on various diseases. The aim of this study was to investigate the serum AGE-2 levels in Vogt-Koyanagi-Harada (VKH) disease. METHODS: Sera were obtained from 31 patients with active VKH. 20 of these 31 patients were treated with systemic corticosteroids. As controls, 33 healthy volunteers were also examined. The serum AGE-2 levels were determined with a competitive enzyme linked immunosorbent assay using AGE-2 polyclonal antibody. RESULTS: The mean AGE-2 level in the sera of patients with VKH disease was 4.91 (SD 2.23) U/ml, which was significantly lower than that of the healthy control subjects (8.32 (2.94), p<0.001). The average serum AGE-2 level significantly increased to 13.49 (2.17) U/ml after the patients were treated with systemic corticosteroids (p<0.001). CONCLUSIONS: These results suggest that AGE-2 may be involved in the onset of VKH disease.

Acute Disease↗
PubMed2003

Activities of sitafloxacin (DU-6859a), either singly or in combination with rifampin, against Mycobacterium ulcerans infection in mice.

Efficacy of a new fluoroquinolone, sitafloxacin (DU-6859a), against Mycobacterium ulcerans was evaluated in vivo using the mouse footpad system. The growth of M. ulcerans in mouse footpads was completely inhibited when mice were fed with sitafloxacin at a dose of 25 mg/kg body weight per day; on the other hand similar effects were observed with ofloxacin at a dose of 100 mg/kg body weight per day. In the presence of rifampin, the above dose of sitafloxacin could be reduced by 75% to achieve total inhibition, while, under similar circumstances, the dose of ofloxacin could be reduced by only 50%. Either used singly or in combination with rifampin, the effects of sitafloxacin were bactericidal. The results suggest that sitafloxacin should be evaluated as a chemotherapeutic agent against M. ulcerans infection.

Animals↗
PubMed2001

Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes.

Monocytes-macrophages are converted to multinucleated giant cells by stimulation with various cytokines, and osteoclasts are the multinucleated giant cells derived from a monocyte-macrophage lineage. However, at present, the fusion peptides have not been clearly identified in monocytes-macrophages. The ADAM are a family of transmembrane glycoproteins that have a role in various biological functions. Interestingly, fertilin-alpha, ADAM9, and ADAM11 have potential fusion peptides. In this study, which ADAM was specifically expressed in monocytes stimulated with anti-CD98 antibody or RANKL and which factor(s) was functioning in monocytes as a fusion protein were investigated. ADAM1, 8, 10, 12, 15, 17, 20, and 21 mRNAs are expressed in blood monocytes incubated with control antibody, anti-FRP-1/CD98 antibody, or RANKL + M-CSF, while ADAM2, 7, 11, 13, 19, 23, 29, and 30 mRNAs could not be detected in these blood monocytes. Expression of ADAM9 and ADAM10 mRNAs are enhanced by either RANKL + M-CSF or anti-CD98 antibody. The expression of ADAM9 and ADAM10 is also induced in blood monocytes by anti-CD98 mAb. An anti-ADAM9 antibody enhances CD98-mediated cell aggregation, while it blocks CD98-mediated and RANKL-mediated multinucleated giant cell formation. A hydroxamate-based metalloprotease inhibitor, SI-27, which is found to suppress ADAM9 activity, suppresses multinucleated giant cell formation. New protein synthesis is necessary for the expression of ADAM9 mRNA and genistein suppresses induction of ADAM9 mRNA. This is the first report that ADAM9 is involved in monocyte fusion, such as CD98-mediated and RANKL-mediated cell fusion of blood monocytes. Furthermore, AMAM9 is one candidate for a fusion peptide in blood monocytes.

ADAM Proteins↗
PubMed2001

Proteolytic analysis of the FliH/FliI complex, the ATPase component of the type III flagellar export apparatus of Salmonella.

The ATPase FliI of the Salmonella type III flagellar protein export apparatus is a 456 amino acid residue cytoplasmic protein consisting of two regions, an N-terminal flagellum-specific region and a C-terminal ATPase region. It forms a complex with a regulatory protein FliH in the cytoplasm. Multi-angle light-scattering studies indicate that FliH forms a homodimer, (FliH)2, and that FliH and FliI together form a heterotrimer, (FliH)2FliI. Mobility upon gel-filtration chromatography gives much higher apparent molecular masses for both species, whereas the mobility of FliI is normal. Sedimentation velocity measurements indicate that both (FliH)2 and the FliH/FliI complex are quite elongated. We have analyzed FliH, FliI and the FliH/FliI complex for proteolytic sensitivity. FliI was degraded by clostripain into two stable fragments, one of 48 kDa (FliI(CL48), missing the first seven amino acid residues) and the other of 46 kDa (FliI(CL46), missing the first 26 residues). Small amounts of two closely spaced 38 kDa fragments (FliI(CL38), missing the first 93 and 97 residues, respectively) were also detected. The FliH homodimer was insensitive to clostripain proteolysis and provided protection to FliI within the FliH/FliI complex. Neither FliI(CL48) nor FliI(CL46) could form a complex with FliH, demonstrating that the N terminus of FliI is essential for the interaction. ATP, AMP-PNP, and ADP bound forms of FliI within the FliH/FliI complex regained sensitivity to clostripain cleavage. Also, the sensitivity of the two FliI(CL38) cleavage sites was much greater in the ATP and AMP-PNP bound forms than in either the ADP bound form or nucleotide-free FliI. The ATPase domain itself was insensitive to clostripain cleavage. We suggest that the N-terminal flagellum-specific region of FliI is flexible and changes its conformation during the ATP hydrolysis cycle.

Adenosine Diphosphate↗
PubMed2001

Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling.

The bacterial flagellar filament is a helical propeller constructed from 11 protofilaments of a single protein, flagellin. The filament switches between left- and right-handed supercoiled forms when bacteria switch their swimming mode between running and tumbling. Supercoiling is produced by two different packing interactions of flagellin called L and R. In switching from L to R, the intersubunit distance ( approximately 52 A) along the protofilament decreases by 0.8 A. Changes in the number of L and R protofilaments govern supercoiling of the filament. Here we report the 2.0 A resolution crystal structure of a Salmonella flagellin fragment of relative molecular mass 41,300. The crystal contains pairs of antiparallel straight protofilaments with the R-type repeat. By simulated extension of the protofilament model, we have identified possible switch regions responsible for the bi-stable mechanical switch that generates the 0.8 A difference in repeat distance.

Crystallography, X-Ray↗
PubMed2001

Three-dimensional MR imaging of mammographically detected suspicious microcalcifications.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value and clinical significance of three-dimensional MR imaging of the breast in patients with mammographically detected suspicious microcalcifications. METHODS: Forty patients with suspicious microcalcifications on mammography were evaluated with three-dimensional MR imaging. MR findings were grouped mainly by distribution of abnormal enhancement (linear, focal-clumped, segmental-clumped, segmental-stippled and diffuse-stippled). These findings were compared with the mammography findings according to the criteria of the Breast Imaging Reporting and Data System (BI-RADS) and histopathologic data. RESULTS: Twenty patients had proven malignancies, most frequently ductal carcinoma in situ. For all the cases, linear (100%) and segmental-clumped type (100%) enhancement on MR imaging showed a significantly higher risk for malignancy. Diffuse stippled type (7%) and no enhancement (0%) on MR imaging indicated the lowest possibility of malignancy. 3D-MR imaging showed a sensitivity of 90%, a specificity of 95% and an overall accuracy of 93% in this study. CONCLUSIONS: Three-dimensional MR imaging of the breast can more accurately diagnose ductal carcinoma in situ. Combined with mammography, this procedure is useful for reducing the number of false-positive biopsies and helpful for deciding the better management of patients with mammographically detected suspicious microcalcifications.

Adult↗
PubMed2001

Distinct structural changes detected by X-ray fiber diffraction in stabilization of F-actin by lowering pH and increasing ionic strength.

Lowering pH or raising salt concentration stabilizes the F-actin structure by increasing the free energy change associated with its polymerization. To understand the F-actin stabilization mechanism, we studied the effect of pH, salt concentration, and cation species on the F-actin structure. X-ray fiber diffraction patterns recorded from highly ordered F-actin sols at high density enabled us to detect minute changes of diffraction intensities and to precisely determine the helical parameters. F-actin in a solution containing 30 mM NaCl at pH 8 was taken as the control. F-actin at pH 8, 30 to 90 mM NaCl or 30 mM KCl showed a helical symmetry of 2.161 subunits per turn of the 1-start helix (12.968 subunits/6 turns). Lowering pH from 8 to 6 or replacing NaCl by LiCl altered the helical symmetry to 2.159 subunits per turn (12.952/6). The diffraction intensity associated with the 27-A meridional layer-line increased as the pH decreased but decreased as the NaCl concentration increased. None of the solvent conditions tested gave rise to significant changes in the pitch of the left-handed 1-start helix (approximately 59.8 A). The present results indicate that the two factors that stabilize F-actin, relatively low pH and high salt concentration, have distinct effects on the F-actin structure. Possible mechanisms will be discussed to understand how F-actin is stabilized under these conditions.

Actins↗
PubMed2001

Roles of partly unfolded conformations in macromolecular self-assembly.

From genes to cells there are many steps of hierarchical increments in building up complex frameworks that provide intricate networks of macromolecular interactions, through which cellular activities such as gene expression, signal processing, energy transduction and material conversion are dynamically organized and regulated. The self-assembly of macromolecules into large complexes is one such important step, but this process is by no means a simple aggregation of macromolecules with predefined, rigid complementary structures. In many cases the component molecules undergo either domain rearrangements or folding of disordered portions, which occurs only following binding to their correct partners. The partial disorder is used in some cases to prevent spontaneous assembly at inappropriate times or locations. It is also often used for finely tuning the equilibrium and activation energy of reversible binding. In other cases, such as protein translocation across membranes, an unfolded terminus appears to be the prerequisite for the process as an initiation signal, as well as the physical necessity to be taken into narrow channels. Self-assembly processes of viruses and bacterial flagella are typical examples where the induced folding of disordered chains plays a key role in regulating the addition of new components to a growing assembly. Various aspects of mechanistic roles of natively unfolded conformations of proteins are overviewed and discussed in this short review.

Bacterial Physiological Phenomena↗
PubMed2001

In vitro induction of CD25+ CD4+ regulatory T cells by the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH).

Recently, we have found that the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) not only suppresses IFN-gamma production, but also induces TGF-beta1 production by activated effector T cells. These alpha-MSH- treated effector T cells function as regulatory T cells in that they suppress IFN-gamma production and hypersensitivity mediated by other effector T cells. Experimental autoimmune uveoretinitis (EAU) was suppressed in its severity and incidence in mice that were injected with primed T cells activated in vitro by APC and antigen in the presence of alpha-MSH. Moreover, it appeared that alpha-MSH had converted a population of effector T cells polarized to mediate hypersensitivity into a population of T cells that now mediated immunoregulation. To characterize these alpha-MSH- treated T cells, primed T cells were TCR-stimulated in the presence of alpha-MSH in vitro and their lymphokine profile was examined. Such effector T cells displayed enhanced levels of TGF-beta1 production and no IFN-gamma or IL-10, with IL-4 levels remaining unchanged in comparison with inactivated T cells. In addition, if soluble TGF-beta receptor II was added to cocultures of alpha-MSH-treated T cells and activated Th1 cells, the alpha-MSH-treated T cells could not suppress IFN-gamma production by the Th1 cells. These results suggest that alpha-MSH induces T cells with a regulatory lymphokine pattern, and that through their production of TGF-beta1 these cells suppress other effector T cells. Examination of the alpha-MSH-treated T cells showed that alpha-MSH did not alter the phosphorylation of CD3 molecules following TCR engagement. Primed T cells express the melanocortin 5 receptor (MC5r), a receptor that is linked to an intracellular signalling pathway shared by other cytokine receptors. Blocking the receptor with antibody prevented alpha-MSH from suppressing IFN-gamma production by the activated regulatory T cells, suggesting that alpha-MSH immunoregulation is through the MC5r on primed T cells. Surface staining and cell sorting of the alpha-MSH- treated primed T cells showed that the regulatory T cells are CD25+ CD4+ T cells. From these results we find that alpha-MSH can mediate the induction of CD25+ CD4+ regulatory T cells. These regulatory T cells require specific antigen for activation, but through non-specific TGF-beta1-mediated mechanisms they can suppress other effector T cells.

Animals↗
PubMed2001

Temporal profiles of the levels of endogenous antioxidants after four-vessel occlusion in rats.

Although it is known that development of lipid peroxidation after ischemia occurs predominantly in vulnerable regions, temporal profiles of antioxidants after ischemia have not been regionally elucidated. After reperfusion periods of 0, 3, 24, and 72 hours following 20 minutes of four-vessel occlusion (n = 6 in each group), the concentration of total glutathione (GSH) and the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) were assayed in the hippocampus, parietal cortex, striatum, thalamus, and brain stem. The levels of all antioxidants were unchanged in all regions without reperfusion; however, the concentration of total GSH significantly decreased in the hippocampus at 3 hours after the onset of reperfusion, and showed a maximum decrease in the hippocampus (68% of the sham-control level), parietal cortex (78% of the sham-control level), and striatum (76% of the sham-control level) after 24 hours of reperfusion. After 72 hours of reperfusion, these regions and the thalamus showed restoration and an increase in the total GSH concentration, respectively. The activities of SOD, GSH-Px, and catalase were stable during the reperfusion period, but the hippocampus showed significant increases in these enzyme activities and the parietal cortex and striatum showed significant increases in SOD activities at 72 hours after the onset of reperfusion. These results indicate that endogenous antioxidants take 72 hours for restoration in vulnerable regions after 20 minutes of four-vessel occlusion in rats.

Animals↗
PubMed2001

[The alternative or simultaneous excretion of different species of mycobacteria in atypical mycobacteriosis--15 cases in 7 years].

Five hundreds and five cases of Mycobacterium tuberculosis infection admitted to our hospital during 7 years from 1993 to 1999. Numbers of newly diagnosed cases were 390, of which 329 (84.4%) were bacilli positive with sputum examination on admission. The recurrent cases were 115, of which 55 (47.8%) were bacilli positive cases. During the same period, mycobacteria other than tuberculosis (atypical mycobacteria) were detected in the sputum of other 121 cases. The 63 (52.1%) out of these 121 cases were diagnosed as atypical mycobacteriosis (AM) due to repetitive detection of bacilli with fulfilled the criteria according to the Japanese Mycobacteriosis Research Group of the National Chest Hospitals. The ratio of 63 AM cases to 329 bacilli positive TB cases was 19.1%, but it range from 8.2% to 31.3% year by year. In these 63 AM cases, 9 (14.3%) cases excreted AM bacilli simultaneously or alternately with TB bacilli. The other 15 (23.8%) cases excreted different AM bacilli simultaneously or alternately. The changes or combinations with M. avium and M. intracellulare were most frequently observed (in 12 cases). The manners of changes and combinations with different species were described in detail.

Humans↗