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Showing papers by "Kumamoto University published in 2007"


Journal ArticleDOI
29 Jun 2007-Cell
TL;DR: It is found that Bim is essential for ER stress-induced apoptosis in a diverse range of cell types both in culture and within the whole animal.

1,335 citations



Journal ArticleDOI
TL;DR: The natural product FR901464 and its methylated derivative, spliceostatin A are shown to inhibit in vitro splicing and promote pre-mRNA accumulation by binding to SF3b, a subcomplex of the U2 small nuclear ribonucleoprotein in the spliceosome.
Abstract: The removal of intervening sequences from transcripts is catalyzed by the spliceosome, a multicomponent complex that assembles on the newly synthesized pre-mRNA. Pre-mRNA translation in the cytoplasm leads to the generation of aberrant proteins that are potentially harmful. Therefore, tight control to prevent undesired pre-mRNA export from the nucleus and its subsequent translation is an essential requirement for reliable gene expression. Here, we show that the natural product FR901464 (1) and its methylated derivative, spliceostatin A (2), inhibit in vitro splicing and promote pre-mRNA accumulation by binding to SF3b, a subcomplex of the U2 small nuclear ribonucleoprotein in the spliceosome. Importantly, treatment of cells with these compounds resulted in leakage of pre-mRNA to the cytoplasm, where it was translated. Knockdown of SF3b by small interfering RNA induced phenotypes similar to those seen with spliceostatin A treatment. Thus, the inhibition of pre-mRNA splicing during early steps involving SF3b allows unspliced mRNA leakage and translation.

570 citations


Journal ArticleDOI
TL;DR: The results demonstrate that the aberrant expression of B7-H1 in urothelial cancer is associated with aggressive tumors, suggesting a regulatory role of tumor-associated B7 H1 in antitumor immunity, and may become a beneficial target for immunotherapy in human uroclinical cancer.
Abstract: Purpose The programmed death-1 (PD-1)/B7-H1 (also called PD-L1) pathway negatively regulates T cell activation and has been suggested to play an important role in regulating antitumor host immunity. To investigate the clinical significance of B7-H1 expression to the tumor grade and postoperative prognosis of patients with urothelial cancer, we analyzed the relationship between B7-H1 expression and various clinicopathological features and postoperative prognosis.

458 citations


Journal ArticleDOI
TL;DR: In this paper, the formation and mechanical properties of Mg 97 Zn 1 RE 2 alloys with long-period stacking ordered (LPSO) structures were investigated by examining RE = Y, La, Ce, Pr, Sm, Nd, Dy, Ho, Er, Gd, Tb and Tm LPSO structures.
Abstract: We investigated the formation and mechanical properties of Mg 97 Zn 1 RE 2 alloys with long-period stacking ordered (LPSO) structures by examining RE = Y, La, Ce, Pr, Sm, Nd, Gd, Dy, Ho, Er, Tb, Tm and Yb The LPSO phase developed for RE = Y, Dy, Ho, Er, Gd, Tb and Tm LPSO Mg-Zn-RE alloys are either type I, in which the LPSO phase forms during solidification: Mg-Zn-Y, Mg-Zn-Dy, Mg-Zn-Ho, Mg-Zn-Er and Mg-Zn-Tm, or type II, in which the LPSO phase is nonexistent in as-cast ingots but precipitates with soaking at 773 K: Mg-Zn-Gd and Mg-Zn-Tb The criteria for REs that form an LPSO phase in Mg-Zn-RE alloys are discussed Mg-Zn-RE alloys with an LPSO phase, which were worked by hot extrusion, include high strength both at ambient and elevated temperatures, and good ductility Their tensile yield strength, ultimate strength and elongation were 342-377 MPa, 372-410MPa and 3-9%, respectively at ambient temperature, and 292-310MPa, 322-345 MPa and 4-13% at 473 K The LPSO Mg-Zn-RE alloys are promising candidates for lightweight structural materials

427 citations


Journal ArticleDOI
TL;DR: In this article, a time-temperature-transformation diagram of an Mg-Zn-Gd alloy is proposed, which shows different precipitation sequences at low, medium and high temperatures.

411 citations


Journal ArticleDOI
TL;DR: It is suggested that the non-canonical Wnt signalling pathway suppresses PPAR-γ function through chromatin inactivation triggered by recruitment of a repressing histone methyltransferase, thus leading to an osteoblastic cell lineage from mesenchymal stem cells.
Abstract: Histone modifications induced by activated signalling cascades are crucial to cell-lineage decisions. Osteoblast and adipocyte differentiation from common mesenchymal stem cells is under transcriptional control by numerous factors. Although PPAR-gamma (peroxisome proliferator activated receptor-gamma) has been established as a prime inducer of adipogenesis, cellular signalling factors that determine cell lineage in bone marrow remain generally unknown. Here, we show that the non-canonical Wnt pathway through CaMKII-TAK1-TAB2-NLK transcriptionally represses PPAR-gamma transactivation and induces Runx2 expression, promoting osteoblastogenesis in preference to adipogenesis in bone marrow mesenchymal progenitors. Wnt-5a activates NLK (Nemo-like kinase), which in turn phosphorylates a histone methyltransferase, SETDB1 (SET domain bifurcated 1), leading to the formation of a co-repressor complex that inactivates PPAR-gamma function through histone H3-K9 methylation. These findings suggest that the non-canonical Wnt signalling pathway suppresses PPAR-gamma function through chromatin inactivation triggered by recruitment of a repressing histone methyltransferase, thus leading to an osteoblastic cell lineage from mesenchymal stem cells.

403 citations


Journal ArticleDOI
TL;DR: The persisting somatoensory disorders after discontinuation of exposure to MeHg were induced by diffuse damage to the somatosensory cortex, but not byDamage to the peripheral nervous system, as previously believed.

343 citations


Journal ArticleDOI
TL;DR: Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria on acute cholecystitis and cholangitis.
Abstract: This article discusses the definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis. Acute cholangitis and cholecystitis mostly originate from stones in the bile ducts and gallbladder. Acute cholecystitis also has other causes, such as ischemia; chemicals that enter biliary secretions; motility disorders associated with drugs; infections with microorganisms, protozoa, and parasites; collagen disease; and allergic reactions. Acute acalculous cholecystitis is associated with a recent operation, trauma, burns, multisystem organ failure, and parenteral nutrition. Factors associated with the onset of cholelithiasis include obesity, age, and drugs such as oral contraceptives. The reported mortality of less than 10% for acute cholecystitis gives an impression that it is not a fatal disease, except for the elderly and/or patients with acalculous disease. However, there are reports of high mortality for cholangitis, although the mortality differs greatly depending on the year of the report and the severity of the disease. Even reports published in and after the 1980s indicate high mortality, ranging from 10% to 30% in the patients, with multiorgan failure as a major cause of death. Because many of the reports on acute cholecystitis and cholangitis use different standards, comparisons are difficult. Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria.

337 citations


Journal ArticleDOI
19 Jul 2007-Nature
TL;DR: It is found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice, and this led to a marked reduction in the absorption rate of nutrients in theSmall intestine, and ultimately to death.
Abstract: A number of proteins are known to be involved in apical/basolateral transport of proteins in polarized epithelial cells. The small GTP-binding protein Rab8 was thought to regulate basolateral transport in polarized kidney epithelial cells through the AP1B-complex-mediated pathway. However, the role of Rab8 (Rab8A) in cell polarity in vivo remains unknown. Here we show that Rab8 is responsible for the localization of apical proteins in intestinal epithelial cells. We found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice. Their mislocalization and degradation in lysosomes led to a marked reduction in the absorption rate of nutrients in the small intestine, and ultimately to death. Ultrastructurally, a shortening of apical microvilli, an increased number of enlarged lysosomes, and microvillus inclusions in the enterocytes were also observed. One microvillus inclusion disease patient who shows an identical phenotype to Rab8-deficient mice expresses a reduced amount of RAB8 (RAB8A; NM_005370). Our results demonstrate that Rab8 is necessary for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine.

323 citations


Journal ArticleDOI
TL;DR: A review of the industrial applications of pulsed power generators is presented in this paper, where the authors classified industrial applications by application for biological effects, for pulsed streamer discharges in gases, for pulses discharging in liquid or liquid-mixture, and for material processing.
Abstract: A review of mainly the past two years is undertaken of the industrial applications of pulsed power. Repetitively operated pulsed power generators with a moderate peak power have been developed for industrial applications. These generators are reliable and have low maintenance. Development of the pulsed power generators helps promote industrial applications of pulsed power for such things as food processing, medical treatment, water treatment, exhaust gas treatment, ozone generation, engine ignition, ion implantation and others. Here, industrial applications of pulsed power are classified by application for biological effects, for pulsed streamer discharges in gases, for pulsed discharges in liquid or liquid- mixture, and for material processing.

Journal ArticleDOI
TL;DR: It is demonstrated that EPA increases adiponectin secretion in rodent models of obesity and human obese subjects, possibly through the improvement of the inflammatory changes in obese adipose tissue.
Abstract: Objectives— Fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) or n-3 PUFAs have been shown to reduce the incidence of coronary heart disease. Here we investigated the effect of highly purifi...

Journal ArticleDOI
TL;DR: It is shown that defects in the PI3K/Pten and Wnt/beta-catenin signaling pathways often occur together in a subset of human OEAs, suggesting their cooperation during OEA pathogenesis.

Journal ArticleDOI
TL;DR: The results suggest that the salt-tolerant P. maritima showed a better protection mechanism against oxidative damage caused by salt stress by its higher induced activities of antioxidant enzymes than the Salt-sensitive P. media.
Abstract: The changes in plant growth, relative water content (RWC), stomatal conductance, lipid peroxidation and antioxidant system in relation to the tolerance to salt stress were investigated in salt-tolerant Plantago maritima and salt-sensitive Plantago media. The 60 days old P. maritima and P. media seedlings were subjected to 0, 100 and 200 mM NaCl for 7 days. Reduction in shoot length was higher in P. media than in P. maritima after exposure to 200 mM NaCl, but 100 mM NaCl treatment did not show any effect on shoot length of P. maritima. Shoot dry weight decreased in P. media and did not change in P. maritima. Two hundred millimolar NaCl treatment had no effect on leaf RWC in P. maritima, but it was reduced in P. media. Salt stress caused reduction in stomatal conductance being more pronounced in P. media than in P. maritima. Activities of superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6), glutathione reductase (GR; EC 1.6.4.2) decreased in P. media with increasing salinity. Ascorbate peroxidase (APX; EC 1.11.1.11) activity in leaves of P. media was increased and showed no change under 100 and 200 mM NaCl, respectively. However, activities of CAT, APX and GR increased under 200 mM NaCl while their activities did not change under 100 mM NaCl in P. maritima. SOD activity in leaves of P. maritima increased with increasing salinity. Concomitant with this, four SOD activity bands were identified in leaves of P. maritima, two bands only were observed in P. media. Peroxidase (POX; EC 1.11.1.7) activity increased under both salt concentrations in P. maritima, but only under 200 mM NaCl in P. media. Confirming this, five POX activity bands were identified in leaves of P. maritima, but only two bands were determined in P. media. Malondialdehyde levels in the leaves increased under salt stress in P. media but showed no change and decreased in P. maritima at 100 and 200 mM NaCl, respectively. These results suggest that the salt-tolerant P. maritima showed a better protection mechanism against oxidative damage caused by salt stress by its higher induced activities of antioxidant enzymes than the salt-sensitive P. media.

Journal ArticleDOI
TL;DR: It is shown that H3K9me1 and 2 are dynamically and sex‐differentially regulated during the meiotic prophase, which strongly suggests that a specific set of H3k9 methyltransferase(s) and demethylase (s) coordinately regulate gametogenesis.
Abstract: Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. G9a is a major mammalian H3K9 methyltransferase at euchromatin and is essential for mouse embryogenesis. Here we describe the roles of G9a in germ cell development. Mutant mice in which G9a is specifically inactivated in the germ-lineage displayed sterility due to a drastic loss of mature gametes. G9a-deficient germ cells exhibited perturbation of synchronous synapsis in meiotic prophase. Importantly, mono- and di-methylation of H3K9 (H3K9me1 and 2) in G9a-deficient germ cells were significantly reduced and G9a-regulated genes were overexpressed during meiosis, suggesting that G9a-mediated epigenetic gene silencing is crucial for proper meiotic prophase progression. Finally, we show that H3K9me1 and 2 are dynamically and sex-differentially regulated during the meiotic prophase. This genetic and biochemical evidence strongly suggests that a specific set of H3K9 methyltransferase(s) and demethylase(s) coordinately regulate gametogenesis.

Journal ArticleDOI
TL;DR: The C. merolae genome contains the smallest known histone-gene cluster, a unique telomeric repeat for all chromosomal ends, and an extremely low number of transposons, which are extremely useful for further studies of eukaryotic cells.
Abstract: All previously reported eukaryotic nuclear genome sequences have been incomplete, especially in highly repeated units and chromosomal ends. Because repetitive DNA is important for many aspects of biology, complete chromosomal structures are fundamental for understanding eukaryotic cells. Our earlier, nearly complete genome sequence of the hot-spring red alga Cyanidioschyzon merolae revealed several unique features, including just three ribosomal DNA copies, very few introns, and a small total number of genes. However, because the exact structures of certain functionally important repeated elements remained ambiguous, that sequence was not complete. Obviously, those ambiguities needed to be resolved before the unique features of the C. merolae genome could be summarized, and the ambiguities could only be resolved by completing the sequence. Therefore, we aimed to complete all previous gaps and sequence all remaining chromosomal ends, and now report the first nuclear-genome sequence for any eukaryote that is 100% complete. Our present complete sequence consists of 16546747 nucleotides covering 100% of the 20 linear chromosomes from telomere to telomere, representing the simple and unique chromosomal structures of the eukaryotic cell. We have unambiguously established that the C. merolae genome contains the smallest known histone-gene cluster, a unique telomeric repeat for all chromosomal ends, and an extremely low number of transposons. By virtue of these attributes and others that we had discovered previously, C. merolae appears to have the simplest nuclear genome of the non-symbiotic eukaryotes. These unusually simple genomic features in the 100% complete genome sequence of C. merolae are extremely useful for further studies of eukaryotic cells.

Journal ArticleDOI
TL;DR: Findings suggest that the reduced neuron-specific expression of the TAF1 gene is associated with XDP, and an abnormal pattern of DNA methylation in the retrotransposon in the genome from the patient's caudate, which could account for decreased expression of TAF 1.
Abstract: X-linked dystonia-parkinsonism (XDP) is a movement disorder endemic to the Philippines. The disease locus, DYT3, has been mapped to Xq13.1. In a search for the causative gene, we performed genomic sequencing analysis, followed by expression analysis of XDP brain tissues. We found a disease-specific SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion in an intron of the TATA-binding protein-associated factor 1 gene (TAF1), which encodes the largest component of the TFIID complex, and significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus. We also identified an abnormal pattern of DNA methylation in the retrotransposon in the genome from the patient's caudate, which could account for decreased expression of TAF1. Our findings suggest that the reduced neuron-specific expression of the TAF1 gene is associated with XDP.

Journal ArticleDOI
TL;DR: Genotype-based EFV dose reduction is feasible in CYP2B6 *6 /*6 and *6/*26 carriers, which can reduce EFV-associated CNS symptoms, and CNS-related symptoms improved with dose reduction in 10 of the 14 patients, although some had not been aware of the symptoms at initial dosage.
Abstract: Background Efavirenz (EFV) is metabolized primarily by cytochrome P450 2B6 (CYP2B6), and high plasma concentrations of the drug are associated with a G-->T polymorphism at position 516 (516G-->T) of CYP2B6 and frequent central nervous system (CNS)-related side effects. Here, we tested the feasibility of genotype-based dose reduction of EFV. Methods CYP2B6 genotypes were determined in 456 human immunodeficiency virus type 1 (HIV-1)-infected patients who were receiving EFV treatment or were scheduled to receive EFV-containing treatment. EFV dose was reduced in CYP2B6 516G-->T carriers who had high plasma EFV concentrations while receiving the standard dosage (600 mg). EFV-naive homozygous CYP2B6 516G-->T carriers were treated with low-dose EFV. In both groups, the dose was further reduced when plasma EFV concentration remained high. Results CYP2B6 516G-->T was identified in the *6 allele (found in 17.9% of our subjects) and a novel allele, *26 (found in 1.3% of our patients). All EFV-treated CYP2B6 *6/*6 and *6/*26 carriers had extremely high plasma EFV concentrations (>6000 ng/mL) while receiving the standard dosage. EFV dose was reduced to 400 mg for 11 patients and to 200 mg for 7 patients with persistently suppressed HIV-1 loads. EFV-containing treatment was initiated at 400 mg in 4 CYP2B6 *6/*6 carriers and one *6/*26 carrier. Two of them still had a high plasma EFV concentration while receiving that dose, and the dose was further reduced to 200 mg, with successful HIV-1 suppression. CNS-related symptoms improved with dose reduction in 10 of the 14 patients, although some had not been aware of the symptoms at initial dosage. Conclusions Genotype-based EFV dose reduction is feasible in CYP2B6 *6/*6 and *6/*26 carriers, which can reduce EFV-associated CNS symptoms.

Journal ArticleDOI
TL;DR: It is demonstrated that statins inhibited lipopolysaccharide-induced tumor necrosis factor α or monocyte chemoattractant protein-1 mRNA expression, and these effects by statins were abrogated by the PPARγ antagonist T0070907 or by small interfering RNA of PPARβ or PPARα.
Abstract: Both statins and peroxisome proliferator-activated receptor (PPAR)gamma ligands have been reported to protect against the progression of atherosclerosis. In the present study, we investigated the effects of statins on PPARgamma activation in macrophages. Statins increased PPARgamma activity, which was inhibited by mevalonate, farnesylpyrophosphate, or geranylgeranylpyrophosphate. Furthermore, a farnesyl transferase inhibitor and a geranylgeranyl transferase inhibitor mimicked the effects of statins. Statins inhibited the membrane translocations of Ras, RhoA, Rac, and Cdc42, and overexpression of dominant-negative mutants of RhoA (DN-RhoA) and Cdc42 (DN-Cdc42), but not of Ras or Rac, increased PPARgamma activity. Statins induced extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) activation. However, DN-RhoA and DN-Cdc42 activated p38 MAPK, but not ERK1/2. ERK1/2- or p38 MAPK-specific inhibitors abrogated statin-induced PPARgamma activation. Statins induced cyclooxygenase (COX)-2 expression and increased intracellular 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) levels through ERK1/2- and p38 MAPK-dependent pathways, and inhibitors or small interfering RNA of COX-2 inhibited statin-induced PPARgamma activation. Statins also activate PPARalpha via COX-2-dependent increases in 15d-PGJ(2) levels. We further demonstrated that statins inhibited lipopolysaccharide-induced tumor necrosis factor alpha or monocyte chemoattractant protein-1 mRNA expression, and these effects by statins were abrogated by the PPARgamma antagonist T0070907 or by small interfering RNA of PPARgamma or PPARalpha. Statins also induced ATP-binding cassette protein A1 or CD36 mRNA expression, and these effects were suppressed by small interfering RNAs of PPARgamma or PPARalpha. In conclusion, statins induce COX-2-dependent increase in 15d-PGJ(2) level through a RhoA- and Cdc42-dependent p38 MAPK pathway and a RhoA- and Cdc42-independent ERK1/2 pathway, thereby activating PPARgamma. Statins also activate PPARalpha via COX-2-dependent pathway. These effects of statins may explain their antiatherogenic actions.

Journal ArticleDOI
TL;DR: 8-nitro-cGMP is revealed to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO.
Abstract: The signaling pathway of nitric oxide (NO) depends mainly on guanosine 3',5'-cyclic monophosphate (cGMP). Here we report the formation and chemical biology of a nitrated derivative of cGMP, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), in NO-mediated signal transduction. Immunocytochemistry demonstrated marked 8-nitro-cGMP production in various cultured cells in an NO-dependent manner. This finding was confirmed by HPLC plus electrochemical detection and tandem mass spectrometry. 8-Nitro-cGMP activated cGMP-dependent protein kinase and showed unique redox-active properties independent of cGMP activity. Formation of protein Cys-cGMP adducts by 8-nitro-cGMP was identified as a new post-translational modification, which we call protein S-guanylation. 8-Nitro-cGMP seems to regulate the redox-sensor signaling protein Keap1, via S-guanylation of the highly nucleophilic cysteine sulfhydryls of Keap1. This study reveals 8-nitro-cGMP to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO.

Journal ArticleDOI
TL;DR: Darunavir contains a privileged, structure-based designed high-affinity P2 ligand, 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF), which has recently been approved for the treatment of HIV/AIDS patients harboring multidrug-resistant HIV-1 variants that do not respond to previously existing HAART regimens.

Journal ArticleDOI
TL;DR: Flow-cytometry and immunofluorescence assays showed that human monocytes bind TWEAK, thus blocking the recognition of CD163 and reducing the activation mediated by a specific mAb in these cells, consistent with the hypothesis that CD163 either acts as a TWE AK scavenger in pathological conditions or serves as an alternate receptor for TWEak in cells lacking Fn14/TweakR.
Abstract: TWEAK (TNF-like weak inducer of apoptosis) is a TNF superfamily member implicated in several mechanisms. Although fibroblast growth factor inducible 14 (Fn14)/TweakR has been reported as its receptor, an as yet unrecognized surface molecule(s) might modulate TWEAK function(s). Thus, we set out to identify TWEAK-binding proteins by screening a combinatorial peptide library. Cyclic peptides containing a consensus motif (WXDDG) bound to TWEAK specifically. These peptides were similar to CD163, a scavenger receptor cysteine-rich domain family member, restricted to the monocyte/macrophage lineage and responsible for the uptake of circulating haptoglobin-hemoglobin (Hp-Hb) complexes. Sequence profile analysis suggested that TWEAK mimicked the CD163 natural ligand (Hp-Hb). Consistently, we show dose-dependent TWEAK binding to CD163 and blockade by an anti-CD163 Ab. In a competition assay, both soluble CD163 and Fn14/TweakR were able to compete off TWEAK binding to coated Fn14/TweakR or CD163, respectively. Flow-cytometry and immunofluorescence assays showed that human monocytes (Fn14/TweakR negative and CD163 positive) bind TWEAK, thus blocking the recognition of CD163 and reducing the activation mediated by a specific mAb in these cells. We demonstrate that monocytes can sequester TWEAK from supernatants, thus preventing tumor cell apoptosis; this effect was reverted by preincubation with the peptide mimicking CD163 or with a mAb anti-CD163, indicating specificity. Finally, we show that recombinant human TWEAK binding to CD163-transfected Chinese hamster ovary cells is inhibited by the presence of either unlabeled TWEAK or the Hp-Hb complex. Together, these data are consistent with the hypothesis that CD163 either acts as a TWEAK scavenger in pathological conditions or serves as an alternate receptor for TWEAK in cells lacking Fn14/TweakR.

Journal ArticleDOI
TL;DR: It is demonstrated that high water temperature treatment suppresses specifically mRNA expression of the forkhead transcription factor gene foxl2, and follicle-stimulating hormone receptor (fshr) in gonads during early sex differentiation and transient transfection assay shows that the flounder Foxl2 and cAMP analog can activate the cyp19a1 gene transcription in vitro.

Journal ArticleDOI
TL;DR: The timing of and the optimal surgical treatment of acute cholecystitis are described in a question-and-answer format and the timing and approach to the surgical management in patients with acute CholecyStitis is still a matter of controversy.
Abstract: Cholecystectomy has been widely performed in the treatment of acute cholecystitis, and laparoscopic cholecystectomy has been increasingly adopted as the method of surgery over the past 15 years. Despite the success of laparoscopic cholecystectomy as an elective treatment for symptomatic gallstones, acute cholecystitis was initially considered a contraindication for laparoscopic cholecystectomy. The reasons for it being considered a contraindication were the technical difficulty of performing it in acute cholecystitis and the development of complications, including bile duct injury, bowel injury, and hepatic injury. However, laparoscopic cholecystectomy is now accepted as being safe for acute cholecystitis, when surgeons who are expert at the laparoscopic technique perform it. Laparoscopic cholecystectomy has been found to be superior to open cholecystectomy as a treatment for acute cholecystitis because of a lower incidence of complications, shorter length of postoperative hospital stay, quicker recuperation, and earlier return to work. However, laparoscopic cholecystectomy for acute cholecystitis has not become routine, because the timing and approach to the surgical management in patients with acute cholecystitis is still a matter of controversy. These Guidelines describe the timing of and the optimal surgical treatment of acute cholecystitis in a question-and-answer format.

Journal ArticleDOI
TL;DR: Both strong fluorescence emission and photochromism properties were concurrent in one system based on a salicylideneaniline derivative and it was suggested that the self-assembly of the functional organogelator could lead to unique photophysical properties.
Abstract: A new organogelator based on a salicylideneaniline derivative with cholesterol moieties was synthesized, and it was proposed that it could gelate various organic solvents, such as 1-butanol, 1-octanol, butyl acetate, tetrachloromethane, benzene, toluene through combination with a gelation test. From the results of analysis by UV/Vis absorption, circular dichroism (CD), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) studies and semiempirical (AM1) calculations, we believed that the gelator molecules could self-assemble into left-handed helical nanofibers through unimolecular layer packing, which further twisted into the thicker fibers and constructed 3D networks in the gel phase. Interestingly, the organogel exhibited strong fluorescence enhancement relative to a solution of the same concentration because of the formation of J aggregations. Meanwhile, photochromism of the organogel could take place under UV-light irradiation. Both strong fluorescence emission and photochromism properties were concurrent in one system based on a salicylideneaniline derivative. It was suggested that the self-assembly of the functional organogelator could lead to unique photophysical properties.

Journal ArticleDOI
TL;DR: Findings indicate that human small intestine and liver show extensive hydrolase activity attributed to CES, which is different from that in species commonly used as experimental animals.

Journal ArticleDOI
15 Feb 2007-Neuron
TL;DR: A model for the lamina-restricted projection of mossy fibers is proposed: the expression of plexin-A4 on mossy fiber prevents them from entering the Sema6A-expressing suprapyramidal region of CA3 and restricts them to the proximal-most part, where Sema 6A repulsive activity is attenuated by plexIn-A2.

Journal ArticleDOI
TL;DR: Epithelial IL‐32α expression was increased in IBD patients, and in CD patients in particular, and might be involved in the pathophysiology of IBD as a proinflammatory cytokine and a mediator of innate immune response.
Abstract: Interleukin (IL)-32 is a recently described proinflammatory cytokine, characterized by induction of nuclear factor (NF)-κB activation. We studied IL-32α expression in the inflamed mucosa of inflammatory bowel disease (IBD). We also investigated mechanisms regulating IL-32α expression. Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n = 10), Crohn's disease (CD) (n = 10), ischaemic colitis (n = 4) and normal colorectal tissues (n = 10). IL-32α expression was evaluated by standard immunohistochemical procedure. IL-32 mRNA expression was analysed by Northern blot. IL-32α was expressed weakly by colonic epithelial cells from normal individuals and subjects with ischaemic colitis. In the inflamed mucosa of IBD patients, epithelial IL-32α expression was increased markedly. In UC and CD patients, IL-32α expression was enhanced in affected mucosa compared to non-affected mucosa. In intestinal epithelial cell lines, expression of IL-32α mRNA and protein was enhanced by IL-1β, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. A combination of TNF-α plus IFN-γ exerted synergistic effects. IL-32α induction by IL-1β and/or TNF-α was mediated by NF-κB activation. Epithelial IL-32α expression was increased in IBD patients, and in CD patients in particular. IL-32α might be involved in the pathophysiology of IBD as a proinflammatory cytokine and a mediator of innate immune response.

Journal ArticleDOI
TL;DR: The data indicate that ZO-1 plays crucial roles not only in TJ formation, but also in the conversion from “fibroblastic’ AJs to belt-like “polarized epithelial” AJs through Rac1 activation, which suggests that Z O-1 is directly involved in the establishment of two distinct junctional domains, belt- like AJs and TJs, during epithelial polarization.
Abstract: The molecular mechanisms of how primordial adherens junctions (AJs) evolve into spatially separated belt-like AJs and tight junctions (TJs) during epithelial polarization are not well understood Previously, we reported the establishment of ZO-1/ZO-2–deficient cultured epithelial cells (1[ko]/2[kd] cells), which lacked TJs completely In the present study, we found that the formation of belt-like AJs was significantly delayed in 1(ko)/2(kd) cells during epithelial polarization The activation of Rac1 upon primordial AJ formation is severely impaired in 1(ko)/2(kd) cells Our data indicate that ZO-1 plays crucial roles not only in TJ formation, but also in the conversion from “fibroblastic” AJs to belt-like “polarized epithelial” AJs through Rac1 activation Furthermore, to examine whether ZO-1 itself mediate belt-like AJ and TJ formation, respectively, we performed a mutational analysis of ZO-1 The requirement for ZO-1 differs between belt-like AJ and TJ formation We propose that ZO-1 is directly involved in the establishment of two distinct junctional domains, belt-like AJs and TJs, during epithelial polarization

Journal ArticleDOI
TL;DR: In this paper, the authors formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade, and formulated flowchart-based management strategies for acute cholangitis and acute cholecystitis.
Abstract: Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient’s general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient’s general medical condition.