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Biomedical subjects

K Nitta

Publications and source records attributed to K Nitta.

At least 19 recordsLinked to original sources

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗

Correlation between the expression level of c-maf and glutathione peroxidase-3 in c-maf -/- mice kidney and c-maf overexpressed renal tubular cells.

Large mafs are transcriptional factors and members of the basic leucine zipper (b-Zip) superfamily. Since we previously identified expression of c-maf in mouse kidney, we presently investigated the mRNA expression profile in the kidney of c-maf gene knockout mice by using DNA microarray, and plasma glutathione peroxidase-3 (GPx3) was predominantly downregulated. We focused on the relation between the expression level of c-maf and GPx3 in vivo and in vitro. Since GPx3 is an antioxidant enzyme, oxidative stress was induced by exposing a culture cell derived from mouse renal tubules (mIMCD3) to hydrogen peroxide. Real-time PCR demonstrated that mRNA expression of both c-maf and GPx3 increased in parallel during exposure to oxidative stress in a time- and dose-dependent manner. Then, the mIMCD3 cells were transfected with c-maf-cDNA containing plasmid, which resulted in an increase in mRNA and protein expression of GPx3 compared with the control cells. Thus, c-maf may be transcriptional regulator of GPx3 expression and modulate the antioxidative pathway in the kidney.

Animals↗

Reduced expression of Toll-like receptor 4 contributes to impaired cytokine response of monocytes in uremic patients.

Toll-like receptors (TLRs) play a pivotal role in pathogen recognition and subsequent cytokine synthesis by immune cells. Uremic patients have a high infectious morbidity, but it remains unclear if this arises from the defective innate immune responses related to TLRs. We studied TLR4 expression in monocytes and their intracellular cytokine synthesis in response to lipopolysaccharide (LPS) stimulation in 35 predialysis patients with chronic kidney disease (CKD) with or without predisposition to bacterial infections and 16 age-matched controls. Expression of TLR4 in unstimulated peripheral monocytes was determined by staining with anti-TLR4 antibody and analysis with flow cytometry. Monocytes were then stimulated by LPS, labeled with anti-CD14 antibody, and subjected to intracellular cytokine staining and flow cytometry. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 synthesis was examined in CD14(+) monocytes. TLR4 expression was constitutively diminished in CKD patients with reduced expression being more severe in those CKD patients who were predisposed to infections. Monocytes from these infection prone CKD patients exhibited significantly reduced synthesis of TNF-alpha, IL-1beta, IL-6, and IL-8 in response to LPS challenge compared with those from control subjects. The intensity of synthesis of each cytokine significantly correlated with TLR4 expression levels in monocytes (P<0.01). The capacity of monocytes to synthesize proinflammatory cytokines was significantly reduced in infection prone CKD patients, and this may possibly be due to the reduced monocyte expression of TLR4. Abnormal TLR4 expression by monocytes may play a role in the susceptibility of such patients to bacterial infections.

Aged↗

Dispersion and dry and wet deposition of PAHs in an atmospheric environment.

The atmospheric concentration and dry and wet deposition were measured for particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) from August to December in Higashi-Hiroshima City, Japan. PM concentration of fine particles (0.6-7 microm) was 5.7-75.1 micro m(-3), and coarse particles (> 7 microm) was 2.2-22.3 microg m(-3). Total PAHs concentration of fine particles was 0.14-16.3 ng m(-3), and coarse particles was 0.01-0.77 ng m(-3). Their concentration increased on non-rainy days and decreased rapidly on rainy days. For seasonal fluctuations of PAHs, their concentrations decreased from summer to winter, and the rate of decrease was more distinct for fine particles. For total (dry + wet) depositions, the PM flux was 1.9-11.2 mg m(-2) d(-1), and the total PAHs flux was 1.9-97.2 ng m(-3) d(-1). From these measurements, the yearly total loading of PAHs was estimated for the particle phase. Total loading was 28 microg m(-2) y(-1) for the dry deposition and 52 mg m(-2) y(-1) for the wet deposition. The loading of the wet deposition was comparable to those of the dry deposition for all ring numbers.

Air Movements↗

Effects of long-term treatment with mizoribine in patients with proliferative lupus nephritis.

AIM: Mizoribine (MZR) is a purine antimetabolic immunosuppressant agent that has few little severe adverse events. We studied whether maintenance therapy with MZR and prednisolone (PSL) in severe proliferative lupus nephritis patients could improve immunity, reduce proteinuria, prevent renal relapse, and reduce steroid dose. METHOD: Long-term maintenance therapy with MZR and PSL was evaluated in ten patients with biopsy-proven proliferative lupus nephritis. Patients with severe lupus nephritis, who had proteinuria of 0.5 g or more even after treatments with plasma exchange and/or pulse methyl prednisolone, were recruited. MZR at an average dose of 140 +/- 10 (100 - 200) mg was administered two to three times/day in combination with PSL. The average period for the MZR maintenance therapy was 89.7 +/- 5.5 (70 - 126) months. Urine protein excretion, serum hemolytic complement activity (CH50), C3, serum creatinine, general and biochemical blood examinations, anti-ds-DNA antibody were collected at each monthly medical examination. RESULTS: All patients were females, mean age 43.0 +/- 3.3 years. A significant decrease in proteinuria was noted two years after the combination therapy (p = 0.0016). Five patients experienced lupus nephritis relapse. Patients who did not experience relapses had their MZR combination therapy initiated earlier (p = 0.037) when compared with the patients who experienced relapses. Serum creatinine levels remained unchanged in all patients throughout treatment and follow-up, even during renal relapses. Levels of C3 and CH50 normalized as proteinuria decreased. None of the patients developed serious side effects during MZR treatment. A significant steroid-sparing effect was observed three years after initiating MZR (p = 0.0025). CONCLUSION: From our long-term observation, maintenance therapy with low-dose PSL combined with MZR can eliminate proteinuria and have steroid-sparing effect. Early initiation of the therapy can protect against renal relapses among severe proliferative lupus nephritis patients without serious side effects.

Adult↗

[The use of fibrous wound dressing sheets made of carboxymethylcellulose natrium in the postoperative management of tracheostomy].

Postoperative management of tracheostomy is very important to reduce several complications such as abnormal granulation and subcutaneous abscess. One of the causes is the use of gauzes and a disinfectant because they induce the secondary wound injury and prevention of wound healing. We used a fibrous wound dressing, carboxymethylcellulose natrium sheet (Aquacel) on the postoperative management of tracheostomy for 5 patients. The sheets were very useful to absorb exudates including blood and to make suitable moist and clean surroundings in all patients.

Aged↗

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗

Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.

A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)</=(3.6x10(-10))micro(B) at 90% C.L. by fitting to the Super-Kamiokande day-night spectra. The fitting took into account the effect of neutrino oscillation on the shapes of energy spectra. With additional information from other solar neutrino and KamLAND experiments constraining the oscillation region, a limit of micro(nu)</=(1.1x10(-10))micro(B) at 90% C.L. was obtained.

Journal Article↗

Search for nu(e) from the sun at Super-Kamiokande-I.

We present the results of a search for low energy nu(e) from the Sun using 1496 days of data from Super-Kamiokande-I. We observe no significant excess of events and set an upper limit for the conversion probability to nu(e) of the 8B solar neutrino. This conversion limit is 0.8% (90% C.L.) of the standard solar model's neutrino flux for total energy=8-20 MeV. We also set a flux limit for monochromatic nu(e) for E(nu(e))=10-17 MeV.

Journal Article↗

Search for supernova relic neutrinos at Super-Kamiokande.

A search for the relic neutrinos from all past core-collapse supernovae was conducted using 1496 days of data from the Super-Kamiokande detector. This analysis looked for electron-type antineutrinos that had produced a positron with an energy greater than 18 MeV. In the absence of a signal, 90% C.L. upper limits on the total flux were set for several theoretical models; these limits ranged from 20 to 130 macro nu(e) cm(-2) s(-1). Additionally, an upper bound of 1.2 macro nu(e) cm(-2) s(-1) was set for the supernova relic neutrino flux in the energy region E(nu)>19.3 MeV.

Journal Article↗

Analysis of nitrogen flow in rice cultivation in CEEF.

In order to control the material circulation in the Closed Ecology Experiment Facilities (CEEF), it is necessary to clarify material flow in the Closed Plant Experiment Facility (CPEF) of CEEF. We tried to grow rice plants and measure the nitrogen contents in rice plant and nutrient solution in plant cultivation bed to trace the material balance in CPEF. The measurements were carried out under the condition of 750 ppm (v/v) CO2 at 26/19 degrees C in the plant cultivation room. The measurements showed the absorbed nitrogen amount in plant was less than the outflow nitrogen amount from nutrient solution. This difference between absorbed and outflow quantity reached to 17%.

Ammonia↗

C4d deposition in the glomeruli and peritubular capillaries associated with transplant glomerulopathy.

Transplant glomerulopathy (TGP) is a unique disease entity with characteristic pathological findings. Although ultrastructural studies for TGP have been performed, histogenesis of TGP is not fully understood. The present study was designed to investigate the relation of complement fragment C4d to the histogenesis of TGP. Nine cases of isolated TGP were randomly selected. A commercially available monoclonal antibody against complement fragment C4d was used in allograft biopsies. To evaluate the extent and severity of deposition of the C4d complement in the glomerular and peritubular capillaries, indirect immunofluoresce method was performed on frozen sections. Intense deposition of C4d in the glomerular basement membrane and peritubular capillaries was found in association with morphological appearance of TGP. Peritubular capillaries were affected in all the patients, showing splitting and multilayering of peritubular capillary basement membrane. These changes, which diffusely affect most capillaries, and their severity pattern were quite similar in each patient. In early stages of all patients with cellular rejection, C4d was not detected in the glomerular and peritubular capillaries. In addition, no C4d deposition was detected in all zero-hour biopsies without diagnostic abnormality. These findings suggest that C4d deposition in the glomerular and peritubular capillaries might be associated with the pathogenesis of TGP in renal transplantation.

Adult↗

Glomerular crescents predominantly express cadherin-catenin complex in pauci-immune-type crescentic glomerulonephritis.

AIMS: To investigate the expression of the cadherin complex in human crescentic glomerulonephritis to elucidate the role of intercellular adherens junction molecules in crescent formation. METHODS AND RESULTS: Immunostaining revealed cadherin complexes localized in Bowman's epithelial cells, but not in podocytes, of normal human glomeruli. Eight adult cases with myeloperoxidase anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA)-related (pauci-immune type) crescentic glomerulonephritis were examined on immunofluorescence microscopy with anti-pan cadherin, p120 catenin, and beta-catenin antibodies. The specimens provided six cellular crescents, 12 fibrocellular crescents, and four fibrotic crescents. Immunofluorescence was semiquantitatively estimated by the rate of the field of localization within the whole area of the crescent, according to the four-grade system [(-) - (++)]. All the tested molecules consisting of the cadherin complex were abundantly observed in cytokeratin-positive epithelial components in crescents, each with an equivalent area of localization. The expression of the cadherin complex was closely associated with that of cytokeratin and both diminished as the crescents developed from cellular to fibrotic. CONCLUSIONS: The cadherin-catenin complex is a specific marker of Bowman's epithelial cells in human glomeruli. The cellular crescents in pauci-immune-type crescentic glomerulonephritis possess adherens junction molecules, indicating a principle parietal epithelial cell phenotype.

Adherens Junctions↗

Catheter dysfunction and thrombosis of double-lumen hemodialysis catheters placed in the femoral vein.

OBJECTIVE: Intraluminal thrombosis of the catheter was thought to be a major cause of catheter dysfunction. We evaluated if thrombi appear in the luminal side or outside of the catheters placed in the femoral vein in 21 hemodialysis patients. METHODS: 23 double-lumen catheter (25 cm long and 4 mm diameter polyurethane) strippings were consecutively performed. Mean catheter dwell time was 17.9 +/- 11.2 days (2-45 days). The femoral vein was observed with ultrasound echography, and thrombo-venous ratio (thrombus diameter/vein diameter) was calculated. X-rays were also taken to clearly visualize the thrombi followed by contrast medium injection through the catheter. RESULTS: Tube-shaped thrombi were echographically detected in 22 of 23 catheters (95.7%) when the catheter was stripped. Ten catheters (43.5%) were stripped due to the reduced blood flow, and tube-shaped thrombi were observed in the femoral vein, whereas no thrombus was found in the intraluminal side of the catheter. In 7 of 23 patients (30.4%) with leg edema on the same side of the catheter, the thrombovenous ratio was 78.9 +/- 7.4%, which was higher than that in the patients without leg edema (52.1 +/- 11.1%). CONCLUSION: The tube-shaped thrombi, formed around the double-lumen catheter, may cause catheter dysfunction and reduced venous return of the lower legs. The catheter should be removed as soon as thrombosis is diagnosed, especially when accompanied by leg edema.

Aged↗

Involvement of MAP kinase cascades in Smad7 transcriptional regulation.

Smad7 transcription is known to be regulated by TGF-beta to form a negative-feedback loop of TGF-beta-mediated biological responses. In this study, we sought to determine whether other signaling cascades, especially mitogen-activated protein (MAP) kinases, might be involved in the transcriptional regulation of Smad7. Hyperosmolarity (500 mOsm/kg H(2)O) or anisomycin (10 microg/ml) potentiated TGF-beta-induced increases of Smad7 mRNA abundance in normal rat kidney fibroblasts. SB203580 (10 microM) treatment had no effect on basal and TGF-beta-induced Smad7 mRNA abundance, and the overexpression of kinase-negative ATF2 had no effect on Smad7 promoter activity. On the other hand, overexpression of dominant-negative JNK and dominant-negative c-Jun significantly attenuated the TGF-beta-induced increases of Smad7 mRNA abundance and promoter activity, respectively. Mutations of the AP-1 element near the Smad-binding element in the rat Smad7 promoter also completely abolished TGF-beta-induced Smad7 promoter activity. These results suggested that the JNK cascade, not p38 kinase, cooperated with the Smad signaling to induce Smad7 transcription through the AP-1 element. Serum treatment (10%) attenuated the TGF-beta-induced Smad7 mRNA increase, and PD98059 (30 microM) treatment increased the basal and TGF-beta-induced Smad7 promoter activity. Gel shift analysis revealed that serum treatment decreased the amount of nuclear Smad complex that PD98059 treatment was shown to restore. These results indicated that ERK activation negatively regulated Smad7 transcription possibly by inhibiting translocation of Smad complex to nuclei. In conclusion, JNK cascade and ERK cascade are important positive and negative regulators of Smad7 transcription, respectively.

Animals↗

Opposing effects of anti-activation-inducible lymphocyte-immunomodulatory molecule/inducible costimulator antibody on the development of acute versus chronic graft-versus-host disease.

The functional role of inducible costimulator (ICOS)-mediated costimulation was examined in an in vivo model of alloantigen-driven Th1 or Th2 cytokine responses, the parent-into-F(1) model of acute or chronic graft-vs-host disease (GVHD), respectively. When the Ab specific for mouse ICOS was injected into chronic GVHD-induced mice, activation of B cells, production of autoantibody, and development of glomerulonephritis were strongly suppressed. In contrast, the same treatment enhanced donor T cell chimerism and host B cell depletion in acute GVHD induced host mice. Blocking of B7-CD28 interaction by injection of anti-B7-1 and anti-B7-2 Abs inhibited both acute and chronic GVHD. These observations clearly indicate that the costimulatory signal mediated by CD28 caused the initial allorecognition resulting in the clonal expansion of alloreactive T cells, whereas the costimulatory signal mediated by ICOS played a critical role in the functional differentiation and manifestation of alloreactive T cells. Furthermore, treatment with anti-ICOS Ab selectively suppresses Th2-dominant autoimmune disease.

Acute Disease↗

Pressure effect on denaturant-induced unfolding of hen egg white lysozyme.

The influence of hydrostatic pressure (< or =100 MPa) on denaturant-induced unfolding of hen egg white lysozyme was investigated by means of ultraviolet spectroscopy at various temperatures. Assuming a two-state transition model, the dependence of Gibbs free-energy change of unfolding on the denaturant concentration was calculated. Under applied hydrostatic pressure, these data were interpreted as suggesting that a two-state model is not applicable in a restricted temperature range; the dominant effect of hydrostatic pressure is to affect the cooperativity in protein unfolding due to a chemical equilibrium shift in the direction of the reduction in the system volume. The deviation from the two-state transition model appears to be rationalized by assuming that applied pressure induces an intermediate conformation between the native and unfolded states of the protein. The implication of the thermodynamic stability of protein under pressure was discussed.

Animals↗

Carbohydrate recognition of gramicidin S analogues in aqueous medium.

We have designed and synthesized of carbohydrate-binding peptides, gramicidin S analogues. Asn/Asp/Gln and Trp residues in the peptides were employed as the binding sites for carbohydrates by hydrogen-bonding interaction and the creation units for hydrophobic pocket to promote the interaction, respectively. The data of fluorescence spectroscopy and affinity column chromatography indicated that the peptides possessed the binding ability for some carbohydrates in aqueous medium. As a result of 1H NMR study, nuclear Overhauser effects between aromatic side chains of a peptide, [Gln(1,1'),Trp(3,3')]-gramisidin S and mannose were observed, indicating that the interaction of the peptide with the sugar occurred in the hydrophobic environment formed by Trp and Phe residues.

Bacillus↗