ABSTRACT
We investigate low-temperature electronic properties of the nondimeric organic superconductor ß^{''}-(ET)_{4}[(H_{3}O)Ga(C_{2}O_{4})_{3}]PhNO_{2}. By examining ultrasonic properties, charge disproportionation (CD) without magnetic field dependence is detected below T_{CD}â¼8 K just above the superconducting critical temperature T_{c}â¼6 K. From quantum oscillations in high fields, we find variation in the Fermi surface and mass enhancement induced by the CD. Heat capacity studies elucidate that the superconducting gap function is fully gapped in the Fermi surface, but anisotropic with fourfold symmetry. We point out that the pairing mechanism of the superconductivity is possibly dominated by charge fluctuations.
ABSTRACT
We have recently have developed an in-situ multiple-channel depth distribution spectrometer (DDS) that can easily acquire on-site measurements of the depth distribution of specific radioactivities of Cs-134 and Cs-137 underground. Despite considerable improvements in the hardware developed for this device, the quantitative method for determining of radioactivities with this DDS device cannot yet achieve satisfactory performance for practical use. For example, this method cannot discriminate each γ-ray spectra of Cs-134 and Cs-137 acquired by the 20 thallium-doped caesium iodine CsI(Tl) scintillation crystal detectors of the DDS device from corresponding depth levels of underground soil. Therefore, we have applied deep learning neural network (DLNN) as a novel radiation measurement technique to discriminate the spectra and to determine the specific radioactivities of Cs-134 and Cs-137. We have developed model soil layers on a virtual space in Monte-Carlo based PHITS simulations and transported γ-ray radiation generated from a particular single soil layer or multiple layers as radiation sources; next, we performed PHITS calculations of those specific radioactivity measurements for each soil layer using DDS device based on machine learning via the DLNN algorithm. In this study, we obtained informative results regarding the feasibility of the proposal innovative radiation measurement method for further practical use in on-site applications.
Subject(s)
Algorithms , Cesium Radioisotopes/analysis , Computer Simulation , Scintillation Counting/instrumentation , Soil Pollutants, Radioactive/analysis , Spectrometry, Gamma , Feasibility Studies , Humans , Radiation MonitoringABSTRACT
A fundamental issue concerning iron-based superconductivity is the roles of electronic nematicity and magnetism in realising high transition temperature (T c). To address this issue, FeSe is a key material, as it exhibits a unique pressure phase diagram involving non-magnetic nematic and pressure-induced antiferromagnetic ordered phases. However, as these two phases in FeSe have considerable overlap, how each order affects superconductivity remains perplexing. Here we construct the three-dimensional electronic phase diagram, temperature (T) against pressure (P) and isovalent S-substitution (x), for FeSe1-x S x . By simultaneously tuning chemical and physical pressures, against which the chalcogen height shows a contrasting variation, we achieve a complete separation of nematic and antiferromagnetic phases. In between, an extended non-magnetic tetragonal phase emerges, where T c shows a striking enhancement. The completed phase diagram uncovers that high-T c superconductivity lies near both ends of the dome-shaped antiferromagnetic phase, whereas T c remains low near the nematic critical point.
ABSTRACT
OBJECTIVE: To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice. RESEARCH DESIGN AND METHODS: This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period. RESULTS: A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by -2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12. CONCLUSION: This is a first report to evaluate the risk-benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk-benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real-world practice. Limitations of this study were those inherent to open-label and non-interventional study designs. TRIAL REGISTRATION: This registry survey is registered at umin.ac.jp (identifier: UMIN000015901).
Subject(s)
Acetaminophen/administration & dosage , Analgesics, Opioid/administration & dosage , Chronic Pain/drug therapy , Tramadol/administration & dosage , Adult , Aged , Aged, 80 and over , Analgesics, Non-Narcotic/administration & dosage , Female , Humans , Japan , Male , Middle Aged , Pain Measurement , Prospective Studies , Tablets , Treatment Outcome , Young AdultABSTRACT
Activities were introduced in Kashiwa city in the Tokyo metropolitan area to correspond to the elevated environmental radiation level after the disaster of the Fukushima Daiichi nuclear power plant. These were based on a strong cooperation between local governments and experts. Ambient dose rate and radioactivity of foodstuff produced inside of the city have been monitored. Representative ambient dose rates around living environments have almost already become their original levels of the pre-accident because of the decontamination activity, natural washout and effective half-lives of radioactivity. The internal annual dose due to radioactive cesium under the policy of 'Local Production for Local Consumption' is estimated as extremely low comparing the variation range due to natural radioactivity. Systematic survey around a retention basin has been started. All of these latest monitoring data would be one of the core information for the policy making as well as a cost-benefit discussion and risk communication.
Subject(s)
Cooperative Behavior , Food Contamination, Radioactive/analysis , Fukushima Nuclear Accident , Local Government , Radiation Protection/methods , Radioactive Fallout/analysis , Decontamination/methods , Expert Testimony/methods , Food Contamination, Radioactive/prevention & control , Interinstitutional Relations , Radioactive Fallout/prevention & control , Safety Management/organization & administrationABSTRACT
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a fundamental process governing not only morphogenesis in multicellular organisms, but also cancer progression. During EMT, epithelial cadherin (E-cadherin) is downregulated while neural cadherin (N-cadherin) is upregulated, referred to as 'cadherin switch'. This study aimed to investigate whether cadherin switch promotes cancer progression in cholangiocarcinoma (CC). METHODS: CC cell lines were examined for migration, invasion, and morphological changes with typical EMT-induced model using recombinant TGF-ß1. The changes in E-cadherin and N-cadherin expression were investigated during EMT. We also examined E-cadherin and N-cadherin expression in resected specimens from extrahepatic CC patients (n=38), and the associations with clinicopathological factors and survival rates. RESULTS: TGF-ß1 treatment activated cell migration, invasion, and fibroblastic morphological changes, especially in extrahepatic CC HuCCT-1 cells. These changes occurred with E-cadherin downregulation and N-cadherin upregulation, that is, cadherin switch. Patients with low E-cadherin expression had a significantly lower survival rate than patients with high E-cadherin expression (P=0.0059). Patients with decreasing E-cadherin and increasing N-cadherin expression had a significantly lower survival rate than patients with increasing E-cadherin and decreasing N-cadherin expression (P=0.017). CONCLUSION: Cadherin switch promotes cancer progression via TGF-ß-induced EMT in extrahepatic CC, suggesting a target for elucidating the mechanisms of invasion and metastasis in extrahepatic CC.
Subject(s)
Cadherins/metabolism , Cholangiocarcinoma/pathology , Epithelial-Mesenchymal Transition , Transforming Growth Factor beta/physiology , Aged , Blotting, Western , Cell Proliferation , Cholangiocarcinoma/metabolism , Disease Progression , Electrophoresis, Polyacrylamide Gel , Female , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Male , Microscopy, Confocal , Middle Aged , Signal TransductionABSTRACT
AIM: Short-chain fatty acids (SCFA) stimulate colonic contraction and secretion, which are mediated by an enteric reflex via a mucosal sensing and cholinergic mechanisms. The involvement of G-protein signal transduction was examined in the secretory response to luminal propionate sensing in rat distal colon. METHODS: Mucosa-submucosa and mucosa preparations were used to measure short-circuit current (I(sc)) and acetylcholine (ACh) release respectively. Cholesterol-rich membrane microdomains, lipid rafts/caveolae, were fractionated using a sucrose gradient ultra-centrifugation after detergent-free extraction of the isolated colonic crypt. RESULTS: Luminal addition of methyl-ß-cyclodextrin (10 mm) and mastoparan (30 µm), lipid rafts/caveolae disruptors, significantly inhibited luminal propionate-induced (0.5 mm) increases in I(sc) , but did not affect increases in I(sc) induced by serosal ACh (0.05 mm) or electrical field stimulation (EFS). Luminal addition of YM-254890 (10 µm), a Gα(q/11) -selective inhibitor, markedly inhibited propionate-induced increase in I(sc) , but did not affect I(sc) responses to ACh and EFS. Both methyl-ß-cyclodextrin and YM-254890 significantly inhibited luminal propionate-induced non-neuronal release of ACh from colonocytes. Real-time PCR demonstrated that in mRNA expression of SCFA receptors, GPR 43 was far higher than that of GPR41 in the colon. Western blotting analysis revealed that the cholesterol-rich membrane microdomains that fractionated from colonic crypt cells were associated with caveolin-1, flotillin-1 and Gα(q/11) , but not GPR43. Uncoupling of Gα(q/11) from flotillin-1 in lipid rafts occurred under desensitization of the I(sc) response to propionate. CONCLUSIONS: These data demonstrate that the secretory response to luminal propionate in rat colon is mediated by G-protein on cholesterol-rich membrane microdomains, provably via Gα(q/11) .
Subject(s)
Cholesterol/metabolism , Colon/metabolism , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , Intestinal Mucosa/metabolism , Intestinal Secretions/metabolism , Membrane Microdomains/metabolism , Propionates/metabolism , Acetylcholine/metabolism , Acetylcholine/pharmacology , Animals , Blotting, Western , Centrifugation, Density Gradient , Colon/drug effects , Colon/innervation , Electric Stimulation , GTP-Binding Protein alpha Subunits, Gq-G11/antagonists & inhibitors , GTP-Binding Protein alpha Subunits, Gq-G11/genetics , Intercellular Signaling Peptides and Proteins , Intestinal Mucosa/drug effects , Intestinal Mucosa/innervation , Male , Membrane Microdomains/drug effects , Membrane Potentials , Membrane Proteins/metabolism , Peptides/pharmacology , Peptides, Cyclic/pharmacology , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Receptors, G-Protein-Coupled/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Wasp Venoms/pharmacology , beta-Cyclodextrins/pharmacologyABSTRACT
Fibrillin-1 is the major structural component of extracellular microfibrils. However, the mechanism by which extracellular fibrillin-1 assembles into microfibrils is not fully understood. Fibrillin-1 contains the Arg-Gly-Asp (RGD) motif, which may allow binding to RGD-recognizing integrins. We hypothesized that integrin alphavbeta3 on the cell surface of human periodontal ligament (PDL) fibroblasts may influence fibrillin-1 assembly into cell/matrix layers. We treated PDL fibroblasts with an integrin alphavbeta3-specific antagonist to examine fibrillin-1 assembly. Western blotting and immunofluorescence analysis showed that treatment with the integrin alphavbeta3 antagonist at 5 muM clearly abolished fibrillin-1 deposition. These results provide for the first time evidence that integrin alphavbeta3 regulates extracellular assembly of fibrillin-1, thereby modulating cell-mediated homeostasis of microfibrils.
Subject(s)
Fibroblasts/metabolism , Integrin alphaVbeta3/metabolism , Microfibrils/metabolism , Periodontal Ligament/cytology , Periodontal Ligament/metabolism , Adolescent , Amino Acid Motifs , Amino Acid Sequence , Cells, Cultured , Fibrillin-1 , Fibrillins , Fibroblasts/cytology , Fibroblasts/drug effects , Humans , Integrin alphaVbeta3/antagonists & inhibitors , Microfibrils/chemistry , Microfilament Proteins/chemistry , Microfilament Proteins/metabolism , Oligopeptides , Young AdultABSTRACT
MATERIAL AND METHODS: We subjected periodontal ligament fibroblasts to stretching strain to examine the effects on their formation of oxytalan fibers in cell/matrix layers. RESULTS: Stretching increased the levels of fibrillin-1 and fibrillin-2 by 25% relative to the control, but did not affect the gene expression level of either type of fibrillin. Immunofluorescence and immunogold electron microscopy analysis revealed that bundles of oxytalan fibers became thicker under stretching conditions. CONCLUSION: These results suggest that tension strain functionally regulates microfibril assembly in periodontal ligament fibroblasts and thus may contribute to the homeostasis of oxytalan fibers in periodontal ligaments.
Subject(s)
Dental Stress Analysis , Extracellular Matrix Proteins/physiology , Microfilament Proteins/physiology , Periodontal Ligament/cytology , Blotting, Northern , Blotting, Western , Cells, Cultured , Elastic Tissue/cytology , Electrophoresis, Polyacrylamide Gel , Extracellular Matrix , Fibrillin-1 , Fibrillin-2 , Fibrillins , Homeostasis , Humans , Microfibrils/ultrastructure , Periodontal Ligament/chemistry , Stress, Mechanical , Tensile StrengthABSTRACT
We report 3 cases of left ventriculoplasty (LVP). They were chosen according to classification of the preoperative left venticle (LV) shape; an apex type and anteroseptal type. We think that an apex type has an indication for a Dor operation and the treatment of an anteroseptal type should be chosen between the following 2 methods. One is an overlapping method. It has the advantage of having to use no intracardiac patch which would remain akinetic area. It is therefore suitable for relatively small LV aneurysms without involvement of the proximal diagonal branches. However, it has the disadvantage of having to cut some distal diagonal branches in order to perform the volume reduction. The other method is a septal anterior ventricular exclusion (SAVE) operation. It is suitable for larger LV aneurysms which involve the proximal diagonal branches due to its advantage of being able to perform the LVP without cutting the diagonal branches. However, it has the disadvantage of leaving an akinetic area that corresponds to the intracardiac patch. We believe that choice of the LVP method according to the preoperative LV shape will bring about a better postoperative LV function and shape.
Subject(s)
Cardiovascular Surgical Procedures/methods , Heart Aneurysm/complications , Heart Aneurysm/surgery , Myocardial Ischemia/etiology , Myocardial Ischemia/surgery , Aged , Heart Ventricles/surgery , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
We show that single-walled carbon nanotube (SWNT) bundles emit visible fluorescence in the presence of noble metal nanoparticles and nanorods in the solid state. Conductivity measurements with metallic nanotubes, isolated from pristine SWNTs, show that they become semiconducting in the presence of the metal nanoparticles. Nanoparticle binding increases the defects in the nanotube structures which is evident in the Raman spectra. The metal-semiconductor transition removes the nonradiative decay channels of the excited states enabling visible fluorescence. Nanotube structures are imaged using this emission with resolution below the classical limits.
ABSTRACT
Elastic system fibers, comprised of microfibrils and tropoelastin, are extracellular components of periodontal tissue. During development, the microfibrils act as a template on which tropoelastin is deposited. However, the process of elastic system fiber remodeling is not fully understood. Therefore, we examined whether matrix metalloproteinases (MMPs) are involved in the remodeling of fibrillins (major components of microfibrils) by human gingival fibroblasts and periodontal ligament (PDL) fibroblasts. Gingival and PDL fibroblasts were cultured for 6 weeks. In some cultures, MMP inhibitor or tissue inhibitor of matrix metalloproteinsase-2 (TIMP-2) was added to the medium for an additional 2 weeks. Active MMP-2 (62 kDa) appeared as cell-membrane-associated or in extracellular matrix only in PDL fibroblast cell layers. The addition of MMP inhibitor or TIMP-2 significantly increased fibrillin-2 accumulation in PDL fibroblast cell layers, and decreased the amount of fibrillin-2 fragments, suggesting that active MMP-2 may degrade fibrillin-2, and that MMPs may play a role in the remodeling of elastic system fibers in PDL.
Subject(s)
Gingiva/metabolism , Matrix Metalloproteinase 2/metabolism , Microfibrils/enzymology , Microfilament Proteins/metabolism , Periodontal Ligament/metabolism , Blotting, Western , Cells, Cultured , Elastic Tissue/enzymology , Electrophoresis, Polyacrylamide Gel , Fibrillin-2 , Fibrillins , Fibroblasts/metabolism , Gingiva/cytology , Humans , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase Inhibitors , Microfilament Proteins/analysis , Periodontal Ligament/cytology , Tissue Inhibitor of Metalloproteinase-2/physiologyABSTRACT
BACKGROUND: Bacterial infection occasionally exacerbates asthma, although the cellular and molecular mechanisms have not been well defined. An involvement of mast cells has been suggested, as lipopolysaccharides (LPS)-induced cytokine production from mast cells in vitro. OBJECTIVE: This study was undertaken to examine the effects of LPS inhalation on mast cell functions and allergen-specific immune responses in a murine model of asthma. METHODS: Female BALB/c mice or mast cell-deficient W/W(v) mice were immunized intraperitoneally with ovalbumin (OVA). Mice were challenged with aerosolized OVA or OVA with LPS daily from day 21 to day 24. Twenty-four hours after the last challenge, airway inflammation and OVA-specific immune responses were examined. Allergen-specific T cell responses were further analysed by adoptively transferring OVA-specific CD4(+) T cells. Expression of chemokines in the lung was also examined. RESULTS: LPS inhalation with OVA resulted in exacerbated airway infiltration, which was not evident in mast cell-deficient mice. IL-5 production by mast cells in the lung was enhanced by LPS inhalation. OVA-specific IgE production as well as proliferation, cytokine production and local infiltration of OVA specific T-helper lymphocytes type 2 (Th2) were also enhanced. Up-regulated expression of Th2- and/or eosinophil-attracting chemokines was observed in the lung of mice inhalated with LPS. CONCLUSIONS: LPS inhalation exacerbates airway inflammation, which is accompanied by mast cell activation and enhanced Th2 responses. These observations provide clues towards understanding the mechanisms of bacterial infection-induced exacerbation of the clinical features of asthma.
Subject(s)
Asthma/immunology , Lipopolysaccharides/adverse effects , Mast Cells/immunology , Th2 Cells/immunology , Allergens/immunology , Animals , Bacterial Infections/immunology , Cytokines/immunology , Disease Models, Animal , Female , Lipopolysaccharides/immunology , Mice , Mice, Inbred BALB C , Respiratory Tract Infections/immunologyABSTRACT
BACKGROUND: Products from the fermentation process of soybeans by Bacillus subtilis (natto) have been shown to possess anti-tumour and immunomodulatory activities. However, the formulations previously examined were not chemically pure, and this is a major limitation for elucidation of the molecular mechanisms for their activities. OBJECTIVE: In order to determine which components in soybean mucilage exert immunostimulatory activities, we examined the activities of their purified forms in vitro and in vivo in mice. METHODS: B. subtilis (natto) and fractions including levan and poly-gamma-glutamic acid (gamma-PGA) from fermented soybean mucilage were prepared. Levels of cytokine production by mouse macrophage cells after treatment with the fractions were measured by means of ELISA. In vivo effect of levan delivered intragastrically on ovalbumin (OVA)-specific T-helper type 2 (Th2) response with IgE production was examined in BALB/c mice that had been immunized intraperitoneally with OVA. Results Levan but neither gamma-PGA nor killed B. subtilis (natto) was found to exert strong activity to induce production of IL-12 p40 and TNF-alpha by macrophage cell lines in vitro. RESULTS: of experiments using Toll-like receptor (TLR) 4-deficient mice and TLR4-transfected human cell line indicated that TLR4 is involved in pattern recognition of levan. Oral administration of levan in vivo significantly reduced the serum levels of OVA-specific IgE and Th2 response to OVA in mice immunized with OVA. CONCLUSION: Levan is an immunostimulatory moiety in products from the fermentation process of B. subtilis (natto) and may be useful for prevention of allergic disorders with IgE production.
Subject(s)
Adjuvants, Immunologic/pharmacology , Fructans/immunology , Glycine max , Plant Extracts/immunology , Signal Transduction/physiology , Toll-Like Receptor 4/metabolism , Animals , Bacillus subtilis , Cell Line , Fermentation , Fructans/analysis , Fructans/pharmacology , Immunoglobulin E/biosynthesis , Interferon-gamma/metabolism , Interleukin-12/immunology , Interleukin-4/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Plant Extracts/pharmacology , Polyglutamic Acid/analysis , Polyglutamic Acid/immunology , Th2 Cells/immunology , Th2 Cells/metabolismABSTRACT
BACKGROUND AND AIMS: Interleukin (IL)-15 is a member of the IL-2 family, stimulating dendritic cells, natural killer (NK) cells, NK T cells and memory CD8+ T cells. IL-15 levels were elevated in the intestinal mucosa of inflammatory bowel diseases. Here we investigated the involvement of IL-15 in the pathogenesis of acute and chronic dextran sulphate sodium (DSS) induced colitis. METHODS: IL-15 knockout (KO) mice and control C57BL/6 mice were used to induce colitis with DSS in their drinking water. Survival rate, clinical activity of diseases, extent of tissue damage, leucocyte population, and cytokine production of lamina propria (LP) cells of the large intestines were assessed. RESULTS: IL-15 KO mice exhibited resistance to DSS induced acute colitis, as reflected by lower lethality, weight loss, clinical scores, and histological scores compared with those in control mice (p<0.05). The proportions of CD44(high) CD8+ T cells and NK cells in LP cells and levels of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, and IL-12p40 in culture supernatants of LP cells were reduced in IL-15 KO mice (p<0.05). In vivo depletion of CD8+ T cells and NK cells decreased levels of IFN-gamma, TNF-alpha, and IL-12p40 in culture supernatants of LP cells in C57BL/6 mice (p<0.01). In chronic colitis, weight loss and clinical scores were improved and levels of IFN-gamma, TNF-alpha, and IL-12p40 in culture supernatants of LP cells were also reduced in IL-15 KO mice (p<0.05). CONCLUSIONS: IL-15 plays an important role in the pathogenesis of both acute and chronic colitis induced by DSS in mice.
Subject(s)
Colitis/immunology , Interleukin-15/immunology , Acute Disease , Animals , Chronic Disease , Colitis/chemically induced , Colitis/pathology , Colon/immunology , Cytokines/biosynthesis , Dextran Sulfate , Disease Models, Animal , Interleukin-15/genetics , Intestinal Mucosa/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Survival Rate , Weight LossABSTRACT
BACKGROUND AND AIMS: Surgical management of extrahepatic cholestasis is frequently complicated by bacterial translocation and severe liver injury. The aim of this study was to clarify the involvement of Toll-like receptors (TLRs) in the pathogenesis of bacterial translocation and liver injury in obstructive cholestasis. METHODS: TLR2 deficient (TLR2(-/-)), MyD88(-/-), Jalpha281(-/-), gld/gld, and lpr/lpr mice, all of which have a C57BL/6 background, and C3H/HeN and TLR4 mutated C3H/HeJ mice were subjected to bile duct ligation (BDL). Faecal IgA and serum alanine aminotransferase levels were determined after BDL. Apoptosis was examined by histological and flow cytometric analyses of cells from Peyer's patches and the liver. RESULTS: The size and number of B cells in Peyer's patches markedly decreased on day 3 after BDL. Increased apoptosis in Peyer's patch B cells was evident on day 1 after BDL in control mice but not in lpr/lpr, MyD88(-/-), or C3H/HeJ mice. On the other hand, TLR2 and Fas ligand expression on intrahepatic NK1.1(+) T cells increased on day 1 after BDL in C57BL/6 mice. Liver injury and apoptosis were evident on day 1 after BDL in control and C3H/HeJ mice but were significantly reduced in TLR2(-/-), Jalpha281(-/-), gld/gld, and lpr/lpr mice. CONCLUSIONS: TLR4 and TLR2 may play important roles in Fas dependent apoptosis in Peyer's patch B cells and hepatocytes, respectively, at an early stage after BDL in mice.
Subject(s)
Cholestasis, Extrahepatic/pathology , Hepatocytes/pathology , Peyer's Patches/pathology , Toll-Like Receptor 2/physiology , Toll-Like Receptor 4/physiology , Alanine Transaminase/blood , Animals , Apoptosis , B-Lymphocytes/pathology , Bacterial Translocation , Cholestasis, Extrahepatic/metabolism , Cholestasis, Extrahepatic/microbiology , Cholestasis, Extrahepatic/surgery , Fas Ligand Protein , Feces/chemistry , Female , Hepatocytes/immunology , Immunoglobulin A/metabolism , Killer Cells, Natural/metabolism , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Mutant Strains , Peyer's Patches/immunology , Tumor Necrosis Factors/metabolism , fas Receptor/physiologyABSTRACT
Autologous fibrin sealant (AFS) which is not based on the conventional method of co-administering fibrinogen, thrombin and aprotinin was prepared by Vivostat system, and was used in coronary artery bypass grafting (CABG). The purpose of this study was to investigate the safety and efficacy of the AFS prepared by the Vivostat system. In 6 of 68 cases of CABG, normal AFS was not prepared due to device failures. AFS was prepared and sprayed in 62 cases. There were the total of 230 anastomosis sprayed AFS and the bleeding could not seen in 225 anastomosis. Surgical hemostatic procedures (4 cases) were or other sealant usage (1 case) was performed 5 bleeding anastomosis sites. The rate of hemostasis at the anastomosis using AFS was 97.8%. This study was conducted in patients undergoing CABG. In this group of patients, a number of commercial available fibrin sealant products are routinely used. The usefulness of Vivostat as medical device to prepare and administer AFS was confirmed in this study.
Subject(s)
Coronary Artery Bypass , Fibrin Tissue Adhesive/standards , Fibrin Tissue Adhesive/therapeutic use , Hemostasis, Surgical , Adult , Aged , Blood Specimen Collection , Female , Humans , Male , Middle AgedABSTRACT
We examined whether or not dietary fructooligosaccharides (FOS) in infancy can have a beneficial effect on the mucosal immune system. Newborn BALB/c mice, accompanied by their dams until 21 days of age, were fed either a control diet based on casein [FOS- diet group] or a FOS- diet supplemented with 5% (w/w) FOS [FOS+ diet group]. Total IgA levels in tissue extracts from the intestines of mice in the FOS+ diet group at 38 days of age were about twofold higher (P < 0.05) than those in the FOS- diet group in the jejunum, ileum and colon. Ileal and colonic polymeric immunoglobulin receptor (pIgR) expression in the FOS+ diet group at 36 days of age was 1.5-fold higher than in the FOS- diet group (P < 0.05). Consistent with these results, the ileal IgA secretion rate of the FOS+ diet group at 37 days of age was twofold higher than that of the FOS- diet group (P < 0.05). Moreover, the percentage of B220(+)IgA+ cells in Peyer's patches (PP) was significantly higher in the FOS+ diet group than in the FOS- diet group (6.2%versus 4.3%, P < 0.05), suggesting that isotype switching from IgM to IgA in PP B cells might be enhanced in vivo. Taken together, our findings suggest that dietary FOS increases the intestinal IgA response and pIgR expression in the small intestine as well as the colon in infant mice.
Subject(s)
Dietary Carbohydrates/immunology , Immunoglobulin A/immunology , Intestinal Mucosa/immunology , Oligosaccharides/administration & dosage , Receptors, Polymeric Immunoglobulin/analysis , Animals , B-Lymphocyte Subsets/immunology , Cecum/chemistry , Cells, Cultured , Colon/immunology , Fatty Acids, Volatile/analysis , Ileum/immunology , Jejunum/immunology , Mice , Mice, Inbred BALB C , Oligosaccharides/immunology , Peyer's Patches/immunology , Receptors, Polymeric Immunoglobulin/immunologyABSTRACT
To evaluate the clinical significance of a cytomegalovirus (CMV) antigenemia assay in the prediction and diagnosis of CMV gastrointestinal (CMV-GI) disease after hematopoietic stem cell transplantation (HSCT), 19 allogeneic HSCT recipients developing CMV-GI disease were retrospectively reviewed. All patients were monitored by a CMV antigenemia assay, at least once weekly after engraftment. The median onset of CMV-GI disease occurred 31 days post transplant (range: 19-62). Only four of 19 patients (21%) developed a positive CMV antigenemia test before developing CMV-GI diseases. Although all 19 patients subsequently developed positive CMV antigenemia tests during their clinical courses, the values remained at a low-level in nine (47%) patients. Among the 14 patients in whom results of real-time polymerase chain reaction (PCR) were available, seven (50%) yielded positive results of real-time PCR before developing CMV-GI disease. In contrast to the values of CMV antigenemia, all 14 patients exclusively yielded high viral loads (median: 2.8 x 10(4) copies/ml plasma). We conclude that CMV antigenemia testing has limited value in prediction or early diagnosis of CMV-GI disease, and that real-time PCR could have a more diagnostic significance.
Subject(s)
Antigens, Viral/blood , Cytomegalovirus Infections/diagnosis , Gastrointestinal Diseases/virology , Hematopoietic Stem Cell Transplantation/adverse effects , Adult , Cytomegalovirus/genetics , Cytomegalovirus/immunology , Cytomegalovirus Infections/etiology , DNA, Viral/blood , Female , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/etiology , Humans , Male , Middle Aged , Polymerase Chain Reaction , Predictive Value of Tests , Retrospective Studies , Transplantation, Homologous , Viral Load/methodsABSTRACT
Lymph node hyalinization has been comprehensively investigated using specimens obtained from elderly Japanese and white Americans. Onion-peel lesions and associated meshwork areas were often found in the medullary sinus of the thoracic node (mediastinal-type hyalinization), while eosinophilic, glassy and spotty lesions were consistently seen in B lymphocyte areas of the pelvic node (pelvic-type hyalinization). The mediastinal-type hyalinization was comprised of thin collagen fibrils (ca 50 nm in diameter), whereas the pelvic-type hyalinization had thick fibrils (ca 150 nm in diameter). This difference seemed to be consistent with a difference in composite collagen fibrils of vascular walls between the thoracic and pelvic regions. The pelvic-type hyalinization was often or sometimes seen in other nodes, such as cervical, axillary, abdominal and inguinal nodes, especially in white Americans. The mediastinal-type hyalinization, usually in combination with a sinus filled with anthracotic macrophages, tended to be observed in Japanese more frequently than in white Americans. Anthracosis seemed to be connected to the pathogenesis of the hyalinization. On the other hand, because the lesion was weakly positive for Factor VIII immunohistochemistry and because lesions were located along thin vessels, the pelvic-type hyalinization seemed to originate from vascular degeneration in the nodal cortex. Due to the high incidence and large proportion in total volume of the node, the hyalinization seems to be one of the major events that diminish the nodal filtration function and ruin the node with aging.