Interference Effect between ϕ and Λ(1520) Production Channels in the γp→K

The ϕ-Λ(1520) interference effect in the γp→K^{+}K^{-}p reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between ϕ and Λ(1520) production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when K^{+}K^{-} pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the sqrt[s]=2.1 GeV bump structure in forward differential cross sections for ϕ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

Effects of short-term intensive glycemic control on insulin, glucagon, and glucagon-like peptide-1 secretion in patients with Type 2 diabetes.

BACKGROUND: Short-term intensive insulin therapy (IIT) in patients with Type 2 diabetes mellitus (T2DM) has beneficial effects on insulin secretion. However, IIT effect on glucagon and glucagon-like peptide-1 (GLP-1) secretion is unknown. AIM: We evaluated short-term intensive glycemic control effects on insulin, glucagon, and GLP-1 secretory dynamics in T2DM. MATERIALS AND METHODS: Twenty-six patients with T2DM were hospitalized and treated with IIT for 10-14 days. A meal tolerance test was performed before and after IIT and the differences in serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) as well as plasma glucagon and active GLP-1 levels were evaluated. RESULTS: Glycoalbumin levels decreased significantly from 23.0% before to 19.6% after IIT (p<0.001). However, pre- and post-IIT, IRI and CPR levels were not significantly different; post-IIT glucose levels were significantly decreased. The post-IIT glucagon levels at 0 and 60 min were lower than pre-IIT levels. Moreover, post- IIT area under the curve (AUC) of glucagon significantly reduced from 6755 ± 996 pg/dl · 60 min to 5796 ± 1074 pg/dl · 60 min (p<0.001). Furthermore, post-IIT GLP-1 levels and AUC were significantly higher than pre-IIT values. CONCLUSIONS: Our results suggest that patients with T2DM who received shortterm IIT demonstrated decreased postprandial glucagon levels and increased GLP-1 levels following a meal tolerance test.

Suppressive effect of asbestos on cytotoxicity of human NK cells.

Asbestos, a naturally occurring fibrous mineral, causes malignant mesothelioma (MM). However, it takes a very long time to develop MM, which suggests that effects other than tumorigenicity of asbestos might contribute to the development of MM, and one of the possible targets is anti-tumor immunity. Therefore, we examined the effect of asbestos exposure on human natural killer (NK) cells using the cell line of YT-A1, Peripheral blood mononuclear cells (PBMCs) cultures and specimens from patients with MM. In particular, we focused on expression of NK cell-activating receptors, including NKG2D, 2B4 and NKp46. Analysis of the YT-CB5 subline of YT-A1, cultured with CB for over 5 months, showed a decrease in cytotoxicity with low expressions of NKG2D and 2B4, although there were no decreases after about one month. YT-CB5 showed decreases in phosphorylation of extracellular signal-regulated kinase (ERK) and degranulation stimulated by antibodies to NKG2D. Peripheral blood (PB-) NK cells from MM patients also showed decreased cytotoxicity compared with healthy volunteers (HV), and was accompanied with low expression of NKp46 unlike YT-CB5. PBMCs cultured with CB resulted in decreased expression of NKp46 on NK cells, although this did not occur when using glass wool, an asbestos substitute. These results indicate that asbestos has the potential to suppress cytotoxicity of NK cells. In particular, it is noteworthy that both NK cells from MM patients and those from a culture of PBMCs derived from HVs with asbestos showed the same characteristic of decreased cytotoxicity with low expression of NKp46.

Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients.

Silicosis patients suffer from pulmonary fibrosis caused by silica inhalation, as well as autoimmune diseases known as the adjuvant effects of silica. Caplan syndrome complicated with rheumatoid arthritis (RA) is well known epidemiologically, and the incidence of complicated systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and antineutrophilic cytoplasmic antibody (ANCA)-related nephritis have been reported frequently in silicosis patients. To explore the detailed mechanisms of silica-induced dysregulation of autoimmunity, we had focused on Fas/CD95 and Fas-mediated apoptosis because Fas is one of the most important molecules regarding apoptosis of lymphocytes and its alteration makes some T cells survive longer. Additionally, if the long-survived T cells include the self-recognizing T-cell clones, it is easily thought that autoimmune diseases will appear in this situation. Furthermore, regulatory T cells (Treg) showing CD4+25+ and forkhead box P3 (FoxP3)-positive have been a central player in regulating activation of self- and foreign-antigen recognizing T cells, and it has been reported that activation of Treg causes its higher expression of Fas/CD95. Thus, in this review, we introduce the alteration of Fas and related molecules as found in silicosis and also present the Treg function of the CD4+25+ fraction in peripheral blood mononuclear cells derived from silicosis patients.

Near-threshold Lambda(1520) production by the gamma(p)-->K{+}Lambda(1520) reaction at forward K+ angles.

Differential cross sections and photon-beam asymmetries for the gamma(p)-->K{+}Lambda(1520) reaction have been measured with linearly polarized photon beams at energies from the threshold to 2.4 GeV at 0.6or=5/2 or by a new reaction process, for example, an interference effect with the phi photoproduction having a similar bump structure in the cross sections.

Reductive alteration of the regulatory function of the CD4(+)CD25(+) T cell fraction in silicosis patients.

Causal links have been documented between silica and rheumatoid arthritis, lupus erythematosus, systemic sclerosis and glomerulonephritis. Two different effects of silica have been suggested, an enhanced inflammatory response in the pulmonary region (e.g. activation of alveolar macrophages) and dysregulation of autoimmunity. Based on our previous reports showing in vitro activation of peripheral T cells by silica and reduced regulatory function of the peripheral CD4(+)CD25(+) fraction in which FoxP(3)+ regulatory T cells (Treg) are located, reconstitution of the CD4(+)CD25(+) fraction in silicosis patients (SILs) was investigated. Since T cells in peripheral CD4(+)CD25(+) and CD4(+)CD25(-) (effector T cells; Teff) fractions from SILs showed higher expression of pd-1 (a marker gene for T cell activation) in comparison to that of healthy donors (HDs), chronic T cell activation was considered to have occurred in SILs. In this study, a higher expression of the CD95/Fas molecule in Treg was recorded from silicosis patients (SILs) compared to healthy donors (HDs), and excess loss of FoxP3(+) Treg in freshly isolated peripheral blood mononuclear cells (PBMCs) from SILs relative to HDs was demonstrated when these cells were cultured with silica ex vivo, whereas CD25(+) cells were not reduced due to contamination of activated Teff in the CD4(+)CD25(+) fraction. The activation of both Teff and Treg results in reconstitution of the peripheral CD4(+)CD25(+) fraction, loss of Treg and contamination of activated Teff, resulting in reduction of the number and function of Treg. These results contribute to our understanding of the development of autoimmune diseases found in SILs.

Impairment in cytotoxicity and expression of NK cell- activating receptors on human NK cells following exposure to asbestos fibers.

Asbestos is well-known for its tumorigenic activity, but its effect on anti-tumor immunity remains unclear. Therefore, we prepared a sub-line of YT-A1 human NK cells exposed to chrysotile B (CB) asbestos (YT-CB5) as an in vitro model to analyze the effect of asbestos exposure on NK cells, and examined cytotoxicity and expressions of its related molecules. The cytotoxicity of YT-CB5 against K562 cells decreased compared with the original line of YT-A1 (YT-Org). YT-CB5 exhibited significant decreases in expressions of cell surface NKG2D, 2B4 and intracellular granzyme A. YT-CB5 also exhibited a decrease in the 2B4-dependent cytotoxicity. In addition, the degranulations stimulated via cell surface NKG2D and 2B4 also decreased in YT-CB5. Therefore, peripheral blood NK cells in patients with malignant mesothelioma (MM) were examined and compared with healthy volunteers. NK cells in patients with MM also showed decreases in cytotoxicity against K562. Although the expressions of NKG2D and 2B4 did not decrease in NK cells of MM patients, the expression of cell surface NKp46 decreased. To confirm the effect of asbestos exposure on peripheral blood NK cells, PBMCs were cultured under exposure to CB. NK cells in PBMCs exposed to CB in vitro showed a significant decrease in the expression of NKp46, whereas NK cells and alter the expression of NK cell-activating receptors including NKG2D, 2B4 and NKp46 and intracellular perforin/granzymes.cells in PBMCs exposed to glass wool did not show such a decrease. These results indicate that exposure to asbestos has the potential to impair the cytotoxicity of NK cells and alter the expression of NK cell-activating receptors including NKG2D, 2B4 and NKp46 and intracellular perforin/granzymes.

Near-threshold photoproduction of Lambda(1520) from protons and deuterons.

Photoproduction of Lambda(1520) with liquid hydrogen and deuterium targets was examined at photon energies below 2.4 GeV in the SPring-8 LEPS experiment. For the first time, the differential cross sections were measured at low energies and with a deuterium target. A large asymmetry of the production cross sections from protons and neutrons was observed at backward K+/0 angles. This suggests the importance of the contact term, which coexists with t-channel K exchange under gauge invariance. This interpretation was compatible with the differential cross sections, decay asymmetry, and photon beam asymmetry measured in the production from protons at forward K+ angles.

Two weeks of permanence in negatively-charged air conditions causes alteration of natural killer cell function.

The effects of negatively-charged air conditions were analyzed as one of the approaches to improve health and quality of life. We previously reported that the use of a charcoal coating and application of an electric voltage yielded predominantly negatively-charged particles in an experimental room, and that 2.5 hours of living in these conditions caused a slight activation of the immune system (slight elevation of serum interleukin (IL)-2), regulated blood flow, and stabilized the autonomic nervous system when compared with control conditions (no dominance of negatively-charged particles). In this study, we expanded the previous study and placed 15 subjects in negatively-charged air conditions for two weeks during the night and analyzed various biological parameters. Although individual biological reactions differed from subject to subject, natural killer (NK) cell activity increased significantly following living in negatively-charged air conditions. Taken together, the results of the previous investigation and those of this study show that repeated elevation of IL-2 (although it immediately returned to the baseline level) causes chronic and recurrent stimulation to NK cells and results in the steady activation of NK cells. Negatively-charged air particles may be a good tool to improve health and quality of life.

Soluble interleukin-2 receptor as an indicator of immunological disturbance found in silicosis patients.

Silicosis patients (SILs) possess not only respiratory disorders but also alterations in autoimmunity. To determine an early indicator of immunological disturbance in SILs, the role of serum-soluble interleukin (IL)-2 receptor (sIL-2R) was analyzed. Of ten SILs, immunological clinical parameters such as immunoglobulin (Ig) G, complements, the titer of autoantibodies including anti-nuclear antibodies (ANA), anti-Scl-70 antibody (Ab) and anti-centromere (CM) Ab, and experimental indicators such as serum-soluble Fas, serum IL-2, CD25+ cells in CD4+ or CD8+ fractions, and sIL-2R were divided from respiratory parameters such as percent vital capacity (%VC), percentage of forced expiratory volume in 1 second (FEV1.0%) and v25/Ht (liter/second/m(body height) by a correlation assay. Additionally, a stepwise regression test showed that sIL-2R was correlated with Ig G, ANA and anti-CM Ab. Furthermore, factor analysis revealed that sIL-2R contributed to the subpopulation of SILs with poorer immunological status in the absence of alterations in respiratory status. By defining healthy donors as 1, SILs as 2 and patients with systemic sclerosis as 3 for immunopathological progression status as metric variables, sIL2R and ANA showed a strong positive correlation. This suggests that sIL-2R is a good clinical indicator of immunological disturbance found in SILs without clinical manifestations of any disturbance in autoimmunity. Further analysis using a large-scale number of patients should be performed to confirm these findings.

Cross sections and beam asymmetry for K;{+}Sigma;{*-} photoproduction from the deuteron at E_{gamma}=1.5-2.4 GeV.

The Sigma(1385) resonance, or Sigma;{*}, is well known as part of the standard baryon decuplet with spin J=3/2. Measurements of the reaction gammap-->K;{+}Sigma;{*0} are difficult to extract due to overlap with the nearby Lambda(1405) resonance. However, the reaction gamman-->K;{+}Sigma;{*-} has no overlap with the Lambda(1405) due to its charge. Here we report the first measurement of cross sections and beam asymmetries for photoproduction of the Sigma;{*-} from a deuteron target. The cross sections at forward angles range from 0.4 to 1.2 mub, with a broad maximum near E_{gamma} approximately 1.8 GeV. The beam asymmetries are negative, in contrast with positive values for the gamman-->K;{+}Sigma;{-} reaction.

Decrease in phosphorylation of ERK following decreased expression of NK cell-activating receptors in human NK cell line exposed to asbestos.

YT-CB5, which had been continuously cultured with chrysotile B (CB)asbestos, showed impaired cytotoxicity with decreased expression of NKG2D and 2B4 NK cell-activating receptors. In the present study, the phosphorylation of extracellular signal-regulated kinase (ERK), which is known to induce degranulation downstream of many NK cell-activating receptors, was examined in YT-CB5 by flow cytometry and compared with the control line YT-Org. YT-CB5 exhibited impaired phosphorylation of ERK1/2 induced by the recognition of K562 cells, downstream of a process mediated by Src family kinase and phosphoinositide 3-kinase. YT-CB5 also exhibited impaired phosphorylation of ERK1/2 following incubation with K562 cells in the presence of anti-2B4 antibodies, where co-stimulation by 2B4 augmented the phosphorylation of ERK1/2 in YT-CB5 to a similar degree as in YT-Org. The phosphorylation of ERK1/2 induced by an inhibitor against phosphatase (PP) 1 and PP2A was also lower in YT-CB5 compared with YT-Org. Moreover, bead-bound antibodies to NKG2D, which contribute to cytotoxicity against K562 cells, induced negligible phosphorylation of ERK1/2 in YT-CB5, although antibodies to 2B4 induced a comparatively greater level of phosphorylation. Additionally, peripheral blood (PB-) NK cells with low expression of NKG2D showed lower phosphorylation of ERK1/2 mediated by anti-NKG2D antibodies compared with PB-NK cells with high expression of NKG2D. These results indicate that signal transduction events leading to the phosphorylation of ERK is impaired in YT-CB5 due to decreased expression of NKG2D. Further studies are required to clarify whether this suppressive effect of asbestos exposure on NK cells might promote lung cancer and mesothelioma in people who have inhaled asbestos.

Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma.

AIMS: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma. METHODS: Genomic DNA was extracted from whole blood of normal tension glaucoma (n = 143) and healthy controls (n = 103) of Japanese origin. RESULTS: Fifteen microsatellite markers within and/or near to the GLC1B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations. CONCLUSION: The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma.

Increase of Q-factor in photonic crystal H1-defect nanocavities after closing of photonic bandgap with optimal slab thickness.

We investigate the dependence of quality factor Q of dipole modes in photonic crystal H1-defect nanocavity on the slab thickness and observe an increase of Q even after closing of the photonic bandgap both in numerical simulation and experimentation. This counter intuitive behavior results from the weak coupling between the cavity mode and the 2nd-guided mode in the photonic crystal slab. This is confirmed by computing the overlap between them in the momentum space.

Complexity of the HVR-1 quasispecies and disease activity in patients with hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels. MATERIALS AND METHODS: Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2.5 years by fluorescence single-strand conformation polymorphism and sequence analysis. RESULTS: There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression. CONCLUSION: Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.

Differential cross section and photon-beam asymmetry for the gamma n --> K+ Sigma- reaction at E gamma = 1.5-2.4 GeV.

Differential cross sections and photon-beam asymmetries have been measured for the gamma n --> K+ Sigma- and gamma p --> K+Sigma0 reactions separately using liquid deuterium and hydrogen targets with incident linearly polarized photon beams of E gamma = 1.5-2.4 GeV at 0.6 < cos ThetacmK< 1. The cross section ratio of sigma K+ Sigma-/sigma K+ Sigma0, expected to be 2 on the basis of the isospin 1/2 exchange, is found to be close to 1. For the K+ Sigma- reaction, large positive asymmetries are observed, indicating the dominance of K* exchange. The large difference between the asymmetries for the K+ Sigma- and K+ Sigma0 reactions cannot be explained by simple theoretical considerations based on Regge model calculations.

Local delivery of angiotensin receptor blocker into the kidney ameliorates progression of experimental glomerulonephritis.

Intrarenally synthesized angiotensin II (Ang II) may be involved in the progression of glomerulonephritis, leading to irreversible glomerulosclerosis. There is increasing evidence that systemic angiotensin receptor blocker (ARB) treatment has beneficial effect on the prognosis of progressive glomerulonephritis and diabetic nephropathy. However, the cellular and molecular mechanisms behind this therapeutic effect of ARB remain unclear. In this study, we used a novel strategy of local ARB delivery via type-1 collagen sponge, to treat progressive glomerulonephritis that would result in irreversible glomerulosclerosis in our previously established rat model. At days 9 and 14 after disease induction, mild proteinuria, 20.7+/-4.7 and 10+/-1.3 mg/day, was found. Local ARB treatment reduced proteinuria significantly to 3.19+/-3.2 and 5.25+/-0.95 mg/day (P < 0.01), respectively. Scoring of glomerular matrix expansion and sclerotic index revealed that local ARB treatment significantly ameliorated glomerular pathology. Ang II type 1 receptor mRNA expression was remarkably enhanced in the Ang II group and ARB treatment reversed this effect at 14 days. Local delivery of ARB significantly improved glomerular blood flow levels, compared to the untreated disease control group, from 710+/-18.25 to 859.44+/-22.86 microm/s, respectively. Local delivery of ARB into the kidney affected local RAS and thus improved the renal injury and function in the potentially progressive glomerulosclerosis of rat model.