Continuous partially hydrolyzed guar gum intake reduces cold-like symptoms: a randomized, placebo-controlled, double-blinded trial in healthy adults.

OBJECTIVE: Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by the controlled partial enzymatic hydrolysis of guar gum beans, has various physiological roles. PHGG is expected to influence the immune function and prevent infections. The objective of this study was to examine the effect of continuous ingestion of PHGG for 12 weeks on the development of cold-like symptoms. PATIENTS AND METHODS: A placebo-controlled, double blind, randomized, parallel-group comparative study was conducted. 96 healthy Japanese adults received 5.2 g PHGG or placebo daily for 12 weeks. Cold-like symptoms were assessed based on patient diary, and the levels of short-chain fatty acids (SCFAs) in stool and blood immune markers at baseline and at weeks 6 and 12. RESULTS: The cumulative number of "no symptoms" days for all symptoms was significantly larger in the PHGG than in the placebo group. The result of the analysis by severity of cold-like symptoms also showed significant differences, with the PHGG group having a lower severity of cold-like symptoms. Propionic acid at weeks 6 and 12 and n-butyric acid and total SCFAs at week 12 were significantly higher in the PHGG than in the placebo group. The Interferon-γ level was significantly lower at week 6 in the PHGG than in the placebo group. CONCLUSIONS: PHGG intake may affect immune function and suppress cold-like symptoms through the production of SCFAs in healthy adults.

Design of tangential viewing phase contrast imaging for turbulence measurements in JT-60SA.

A tangential viewing phase contrast imaging system is being designed for the JT-60SA tokamak to investigate microturbulence. In order to obtain localized information on the turbulence, a spatial-filtering technique is applied, based on magnetic shearing. The tangential viewing geometry enhances the radial localization. The probing laser beam is injected tangentially and traverses the entire plasma region including both low and high field sides. The spatial resolution for an Internal Transport Barrier discharge is estimated at 30%-70% of the minor radius at k = 5 cm-1, which is the typical expected wave number of ion scale turbulence such as ion temperature gradient/trapped electron mode.

Hes1 suppresses acute myeloid leukemia development through FLT3 repression.

In leukemogenesis, Notch signaling can be up and downregulated in a context-dependent manner. The transcription factor hairy and enhancer of split-1 (Hes1) is well-characterized as a downstream target of Notch signaling. Hes1 encodes a basic helix-loop-helix-type protein, and represses target gene expression. Here, we report that deletion of the Hes1 gene in mice promotes acute myeloid leukemia (AML) development induced by the MLL-AF9 fusion protein. We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity. FLT3 was consequently upregulated in MLL-AF9-expressing immortalized and leukemia cells with a Hes1- or RBPJ-null background. MLL-AF9-expressing Hes1-null AML cells showed enhanced proliferation and ERK phosphorylation following FLT3 ligand stimulation. FLT3 inhibition efficiently abrogated proliferation of MLL-AF9-induced Hes1-null AML cells. Furthermore, an agonistic anti-Notch2 antibody induced apoptosis of MLL-AF9-induced AML cells in a Hes1-wild type but not a Hes1-null background. We also accessed two independent databases containing messenger RNA (mRNA) expression profiles and found that the expression level of FLT3 mRNA was negatively correlated with those of HES1 in patient AML samples. These observations demonstrate that Hes1 mediates tumor suppressive roles of Notch signaling in AML development, probably by downregulating FLT3 expression.

Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice.

TET2 (Ten Eleven Translocation 2) is a dioxygenase that converts methylcytosine (mC) to hydroxymethylcytosine (hmC). TET2 loss-of-function mutations are highly frequent in subtypes of T-cell lymphoma that harbor follicular helper T (Tfh)-cell-like features, such as angioimmunoblastic T-cell lymphoma (30-83%) or peripheral T-cell lymphoma, not otherwise specified (10-49%), as well as myeloid malignancies. Here, we show that middle-aged Tet2 knockdown (Tet2(gt/gt)) mice exhibit Tfh-like cell overproduction in the spleen compared with control mice. The Tet2 knockdown mice eventually develop T-cell lymphoma with Tfh-like features after a long latency (median 67 weeks). Transcriptome analysis revealed that these lymphoma cells had Tfh-like gene expression patterns when compared with splenic CD4-positive cells of wild-type mice. The lymphoma cells showed lower hmC densities around the transcription start site (TSS) and higher mC densities at the regions of the TSS, gene body and CpG islands. These epigenetic changes, seen in Tet2 insufficiency-triggered lymphoma, possibly contributed to predated outgrowth of Tfh-like cells and subsequent lymphomagenesis. The mouse model described here suggests that TET2 mutations play a major role in the development of T-cell lymphoma with Tfh-like features in humans.

Small ion-temperature-gradient scale length and reduced heat diffusivity at large hydrogen isotope mass in conventional H-mode plasmas.

The dependence of the ion-temperature-gradient scale length on the hydrogen isotope mass was examined in conventional H-mode plasmas in JT-60U tokamak. While identical profiles for density and temperature were obtained for hydrogen and deuterium plasmas, the ion conductive heat flux necessary for hydrogen to sustain the same ion temperature profile was two times that required for deuterium, resulting in a clearly higher ion heat diffusivity for hydrogen at the same ion-temperature-gradient scale length. On the other hand, the ion-temperature-gradient scale length for deuterium is less than that for hydrogen at a given ion heat diffusivity.

Desensitization protocol in highly HLA-sensitized and ABO-incompatible high titer kidney transplantation.

BACKGROUND: A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established. METHODS: We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6-12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab. RESULTS: Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients. CONCLUSIONS: These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation.

Observation of a complex multistage transition in the JT-60U H-mode edge.

A complex multistage transition of the edge radial electric field is observed in JT-60U H-mode phase without edge localized mode. An interesting feature is that the poloidal rotation velocity of the carbon impurity ions changes in the later H-phase without a comparable change in the main ion pressure gradient, indicating a change in the parallel momentum (and particle) balance channel.

Rotation drive and momentum transport with electron cyclotron heating in tokamak plasmas.

The role of electron cyclotron resonance heating (ECRH) on the toroidal rotation velocity profile has been investigated in the JT-60U tokamak device by separating the effects of the change in momentum transport, the intrinsic rotation by pressure gradient, and the intrinsic rotation by ECRH. It is found that ECRH increases the toroidal momentum diffusivity and the convection velocity. It is also found that ECRH drives the codirection (co) intrinsic rotation inside the EC deposition radius and the counterdirection (ctr) intrinsic rotation outside the EC deposition radius. This ctr rotation starts from the EC deposition radius and propagates to the edge region.

Observation of an energetic-particle-driven instability in the wall-stabilized high-beta plasmas in the JT-60U tokamak.

We have observed a bursting mode in the high-beta plasmas above the ideal beta limit without a conducting wall. The mode frequency is chirping down as the mode amplitude increases, and its initial value is close to the precession frequency of the trapped energetic particle from the perpendicular neutral beams. The mode structure is radially extended with a peak around the q = 2 surface. This mode can finally trigger the resistive wall mode (RWM) despite enough plasma rotation for RWM stabilization. It is concluded that the mode is driven by trapped energetic particles. The mode is attributed to the interaction between the trapped energetic particles and a marginally stable mode in the wall-stabilized high-beta_{N} region.

Transition between internal transport barriers with different temperature-profile curvatures in JT-60U Tokamak plasmas.

A spontaneous transition phenomena between two states of a plasma with an internal transport barrier (ITB) is observed in the steady-state phase of the magnetic shear in the negative magnetic shear plasma in the JT-60U tokamak. These two ITB states are characterized by different profiles of the second radial derivative of the ion temperature inside the ITB region (one has a weak concave shape and the other has a strong convex shape) and by different degrees of sharpness of the interfaces between the L mode and the ITB region, which is determined by the turbulence penetration into the ITB region.

Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet.

BACKGROUND: Obesity is a risk factor for acute pancreatitis (AP), but the molecular mechanism remains unclear. Adiponectin, an adipose tissue-derived secretory factor, has anti-inflammatory properties in addition to various biological functions, and its plasma concentrations are reduced in obese subjects. However, the role of adiponectin in AP has not been investigated. AIM: To determine the effects of adiponectin on AP. METHODS: We investigated the effects of adiponectin on experimental AP by using adiponectin-knockout (APN-KO) mice and adenovirus-mediated adiponectin over-expression. AP was induced by 10 hourly intraperitoneal injections of low-dose caerulein (10 microg/kg) after 2 week feeding of normal chow or a high-fat diet (HFD) in wild-type (WT) and APN-KO mice. We evaluated the severity of AP biochemically and morphologically. RESULTS: Low-dose caerulein treatment did not induce pancreatic damage in either WT or APN-KO mice under normal chow feeding. APN-KO mice, but not WT mice, fed a HFD and then treated with caerulein developed pancreatic damage and inflammation, accompanied by increased macrophage/neutrophil infiltration and upregulation of pro-inflammatory mediators such as tumour necrosis factor alpha in the pancreas. Adenovirus-mediated over-expression of adiponectin attenuated the severity of HFD/caerulein-induced AP in APN-KO mice. CONCLUSIONS: Adiponectin plays a protective role in caerulein-induced AP in HFD-fed mice.

Role of pressure gradient on intrinsic toroidal rotation in tokamak plasmas.

The toroidal plasma rotation generated by the external momentum input and by the plasma itself (intrinsic rotation) has been separated through a novel momentum transport analysis in the JT-60U tokamak device. The toroidal rotation, which is not determined by the momentum transport coefficients and the external momentum input, has been observed. It is found that this intrinsic rotation is locally determined by the local pressure gradient and increases with increasing pressure gradient. This trend is almost the same for various plasmas: low and high confinement mode, co and counterrotating plasmas.

Identification of a low plasma-rotation threshold for stabilization of the resistive-wall mode.

The plasma rotation necessary for stabilization of resistive-wall modes (RWMs) is investigated by controlling the toroidal plasma rotation with external momentum input by injection of tangential neutral beams. The observed threshold is 0.3% of the Alfvén velocity and much smaller than the previous experimental results obtained with magnetic braking. This low critical rotation has a very weak beta dependence as the ideal wall limit is approached. These results indicate that for large plasmas such as in future fusion reactors with low rotation, the requirement of the additional feedback control system for stabilizing RWM is much reduced.

Influence of lip support on the soft-tissue profile of complete denture wearers.

Complete dentures change the soft-tissue profile, although the exact relationship remains unclear. This study examined the relationship between the presence and degree of lip support provided by dentures and the lateral views of the facial appearance of edentulous patients. The subjects were five edentulous patients (three men and two women). Their facial appearances with experimental record blocks, with and without their complete dentures, were measured using a three-dimensional laser measuring system. The experimental record block for each subject had different conditions in the anteroposterior direction anteriorly but the same vertical dimensions posteriorly. The lateral digital facial images were displayed on a computer monitor, and the linear and angular measurements were analysed using image analysis software. The nasolabial angle was smaller and the labial points projected more with excessive lip support versus with deficient support. Moreover, the counter of the nose was affected by the labial flange of the record base, particularly in the facial appearance of one subject with highly atrophic residual ridges. The lip support affected the lower facial soft-tissue profile, including the lower part of the nose; the nasolabial angle and positional relationship between the lips and Ricketts's esthetic plane (E plane) are useful indexes for examining lip support.

Accumulation of advanced glycation end products in women with preeclampsia: possible involvement of placental oxidative and nitrative stress.

Advanced glycation end products (AGEs) are known to cause oxidative damage in various cells by binding with its receptor, RAGE. We measured the serum level of AGEs and examined the AGEs, RAGE, and the other biomarkers of oxidative stress in the placentas from preeclamptic women. Competitive ELISA was carried out to measure the AGEs in serum. Western blotting was performed to analyze AGEs and RAGE in the placenta. Immunohistochemical analyses were performed to examine the localization of AGEs, RAGE, and other biomarkers of oxidative stress in the placenta. The mean level of serum AGEs in preeclamptic women was significantly higher than that in healthy non-pregnant women or healthy pregnant women. Western blotting revealed that the level of AGEs or RAGE in preeclamptic placenta was significantly higher than that in normal placenta. Immunohistochemical analyses showed that levels of nitrotyrosine and nitroguanosine, which are formed by reactive nitrogen species, in preeclamptic placenta were higher than those in normal placenta. Accumulation of 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine indicated enhanced oxidative modifications of lipids and DNA in preeclamptic placenta. The AGE-RAGE system, which is upregulated in preeclampsia, is likely to be involved in the oxidative stress of preeclampsia.

Role of bremsstrahlung radiation in limiting the energy of runaway electrons in tokamaks.

Bremsstrahlung radiation of runaway electrons is found to be an energy limit for runaway electrons in tokamaks. The minimum and maximum energy of runaway electron beams is shown to be limited by collisions and bremsstrahlung radiation, respectively. It is also found that a massive injection of a high-Z gas such as xenon can terminate a disruption-generated runaway current before the runaway electrons hit the walls.

Reduced heat transport between edge-localized-mode bursts at low collisionality and small poloidal Larmor radius.

Nondimensional parameter dependence of heat transport between edge localized modes (ELMs) is examined for H mode plasmas. The electron heat diffusivity between ELMs is reduced to the level of ion neoclassical transport in the plasma edge region which is affected by ELM burst. At lower edge collisionality, the heat flux assigned to the heat transport between ELMs is reduced and the ELM loss power is enhanced. During the inter-ELM phase, the energy confinement time becomes larger with decreasing the edge collisionality and poloidal Larmor radius.

Advanced glycation end products induce secretion of chemokines and apoptosis in human first trimester trophoblasts.

BACKGROUND: We studied the effects of advanced glycation end products (AGEs), which are known to accumulate in patients with diabetes, autoimmune diseases, or that smoke, on human trophoblasts. METHODS: First trimester human chorionic villi of 6-10 week gestation were obtained. Expression and localization of the receptor for AGEs (RAGE) was examined by western blotting and immunohistochemistry. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, regulated upon activation, normal T-cell expressed and secreted (RANTES), and human chorionic gonadotropin (hCG) in culture medium were measured by ELISA. Trophoblastic apoptosis was evaluated by the Hoechst 33258 staining and the in situ nick end labeling technique. RESULTS: RAGE was localized in trophoblasts. AGEs significantly stimulated secretion of both MIP-1alpha and MIP-1beta from trophoblasts in a time- and dose-dependent manner. AGEs significantly induced apoptosis and reduced secretion of hCG. Increased secretions of MIP-1alpha and MIP-1beta by AGEs were significantly suppressed by inhibitors of nitric oxide synthase (NOS) or nafamostat mesilate, a synthetic serine protease inhibitor and a suppressor of transcription factor, NF-kappaB activation. These agents also suppressed the effects of AGEs on hCG secretion and trophoblastic apoptosis. CONCLUSIONS: These AGE-mediated changes in trophoblasts may lead to impairment of implantation and placentation. NOS inhibitors or nafamostat mesilate may modify these effects.

Formation of advanced tokamak plasmas without the use of an ohmic-heating solenoid.

A new operational scenario of advanced tokamak formation was demonstrated in the JT-60U tokamak. This was accomplished by electron cyclotron and lower hybrid waves, neutral beam injection, and the loop voltage supplied by the vertical field and shaping coils. The Ohmic heating (OH) solenoid was not used but a small inboard coil (part of the shaping coil), providing less than 20% of total poloidal flux, was used. The plasma thus obtained had both internal and edge transport barriers, with an energy confinement time of 1.6 times H-mode scaling, a poloidal beta of 3.6, and a normalized beta of 1.6, and a large bootstrap current fraction (>90%). This result opens up a possibility to reduce, and eventually eliminate, the OH solenoid from a tokamak reactor, which will greatly improve its economic competitiveness.