Biliobiliary fistula associated with gallbladder carcinoma.
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Adult↗
Biomedical subjects
H Nishio
Publications and source records attributed to H Nishio.
1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) inhibits cyclic GMP-PKG pathway-independent nonadrenergic, noncholinergic relaxation in longitudinal muscle of the rectum of Wistar-ST rats.
Participation of the nitric oxide-cyclic GMP pathway in nonadrenergic, noncholinergic (NANC) relaxation induced by electrical field stimulation of longitudinal muscle of the rectum of Wistar-ST rats was studied by using a selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). ODQ concentration dependently inhibited the relaxation and at 10 microM, maximally inhibited it by 83%. However, results obtained with N(G)-nitro-L-arginine, L-arginine and exogenously added nitric oxide excluded the participation of nitric oxide in the relaxation. An inhibitor of cyclic GMP-dependent protein kinase (PKG) partially (39%) inhibited the relaxation. ODQ also significantly inhibited the relaxation, which persisted after the PKG inhibitor-treatment, by 85%. The results strongly suggest that ODQ inhibits the NANC relaxation in a cyclic GMP-PKG pathway-independent manner.
Animals↗
Possible role of potassium channels in mu-receptor-mediated inhibition and muscarinic autoinhibition in acetylcholine release from myenteric plexus of guinea pig ileum.
It is known that mu-agonists inhibit electrical field stimulation (EFS)-evoked ACh release from longitudinal muscle myenteric plexus (LMMP) preparation of guinea pig ileum when muscarinic autoinhibition does not fully work. In the present study, the possible role of K+ channels in the mechanisms of mu-agonists-induced inhibition and autoinhibition of ACh release was studied. In the presence of atropine, which blocks the autoinhibition, non-selective K+ channel blockers, tetraethylammonium (TEA) and 4-aminopyridine (4-AP), reversed the inhibitory effect of mu-agonists, morphine and [D-Ala2, N-Me-Phe4, Gly5-ol] enkephalin, on EFS-evoked ACh release, but not that of kappa-agonist U-50,488. Apamin, iberiotoxin or glibenclamide did not affect the inhibition of ACh release by morphine. On the other hand, in the absence of atropine (under the autoinhibition working condition), 4-AP increased EFS-evoked ACh release, but atropine did not further increase ACh release in the presence of 4-AP. In contrast, although TEA did not affect EFS-evoked ACh release, atropine increased ACh release in the presence of TEA. These results suggest that the inhibitory effects of mu-agonists and muscarinic autoinhibition on the ACh release are associated with activation of different types of K+ channels in the guinea pig LMMP preparations: the former is associated with 4-AP- and TEA-sensitive K+ channels and the latter is associated with 4-AP- but not TEA-sensitive K+ channels.
4-Aminopyridine↗
Mediators of nonadrenergic, noncholinergic relaxation in Sprague Dawley rat intestine: comparison with the mediators of other strains.
Participation of nitric oxide, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) in nonadrenergic, noncholinergic (NANC) relaxation of longitudinal muscle of various intestinal regions in Sprague Dawley rats (8-week-old) was studied in vitro. Nitric oxide was suggested to participate in NANC relaxation of every intestinal region studied. But the participation was partial and its extent varied among the regions: significant in the proximal colon and rectum, and moderate in the jejunum, ileum and distal colon. Participation of PACAP in NANC relaxation was suggested only in the distal colon, while that of VIP was not detected in any of regions. Results obtained in the present study indicate that extent of participation of nitric oxide in NANC relaxation in Sprague Dawley rat intestine is more significant than those of other strains, Wistar and Wistar-ST.
Animals↗
Mediators and intracellular mechanisms of NANC relaxation of smooth muscle in the gastrointestinal tract.
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Animals↗
[Studies of gastric acid secretion and gastric mucosal change after Helicobacter pylori eradication--the short and long-term observation].
We studied the gastric acid secretion and the histological findings of gastric mucosa in 48 patients with peptic ulcer before and after successful Helicobacter pylori (H. pylori) eradication. The pH of fasting gastric juice significantly decreased from 2.46 to 1.65 four weeks after eradication (p < 0.001). The factors such as disease, atrophic border, inflammatory cell involvement and histological atrophy were analyzed by logistic regression. Only the atrophic border was a significant and independent factor to convert the acidity after eradication, and the pH of gastric juice prominently decreased in the patients with widespread atrophic mucosal area. In the 24-hour intragastric pH monitoring, the pH3 holding time overnight remarkably decreased from 54.1% to 22.3% after eradication (p < 0.005). In the long follow-up of 17 patients (the mean follow-up period was 15.2 months), the pH of gastric juice kept a lower titer of 1.66. The mean atrophic scores in the upper body reduced from 1.5 to 0.9 (p < 0.05). In addition to the functional recovery of parietal cells after eradication, it was considered that the histological improvement of atrophy in oxyntic mucosa was associated with the recovery of pH.
Adult↗
[Evaluation of chemotherapy for gastric cancer by endoscopic ultrasonography].
We judged the efficacy of chemotherapy using endoscopic ultrasonography (EUS) in 26 cases of gastric cancer. Treatment efficacy was evaluated according to the General Rules for the Gastric Cancer Study, based on the reduction of the largest cross-sectional area of the tumor. A reduction of over 50% was rated as U-PR and a reduction of -25-50% was rated as U-NC. Our findings showed U-PR in 11 cases and U-NC in 15 cases. Three cases initially considered to be NC according to the rules were judged to be U-PR based on EUS findings. Marked therapeutic efficacy in these 3 cases was demonstrated clinically and this was confirmed by EUS findings. Generalized Wilcoxon test showed a significant difference in the cumulative survival rate between U-PR and U-NC cases (p < 0.05). EUS provides an objective means of evaluating the efficacy of chemotherapy in gastric cancer patients, including those with lesions that cannot be evaluated by the General Rules for the Gastric Cancer Study.
Adult↗
Epidermal sphingomyelins are precursors for selected stratum corneum ceramides.
Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique omega-hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsible for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer production. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphingomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of beta-glucocerebrosidase. Using gas chromatography-mass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with distinctive amide-linked (N-acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C(22;-26)), short-chain FA (SM-2; primarily C(16)), and short-chain alpha-hydroxy FA (SM-3; C(16;-18)). In contrast, only trace quantities of omega-hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphingosine was not detected. Comparison of these SM with corresponding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. Moreover, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indicate that two epidermal SM, that is, SM-1 and SM-3, are important precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, including the omega-hydroxy Cer species, do not derive from SM.
Animals↗
Molecular genetic analysis and mutation screening of the VHL gene in a Japanese family with von Hippel-Lindau disease.
Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited familial cancer syndrome which predisposes individuals to a variety of malignant and benign tumors. Its penetrance is almost 100% by 61-70 years of age. We have identified a germline mutation in the VHL gene of a Japanese male patient with a retinal hemangioma in the left eye, an intracranial hemangioblastoma, a left renal tumor and bilateral pheochromocytomas. Screening for the mutation was performed in all members of the patient's family at risk for VHL disease. The mutation identified in the patient was a missense mutation at codon 238 (CGG to CAG). The elder daughter, who did not show any clinical symptoms, was found to carry the same mutation. In order to detect and treat tumors in VHL patients at an earlier stage, it is necessary to identify and screen for the VHL gene mutation in all family members known at risk.
Adult↗
[Case of primary racemose hemangioma of the bronchial artery without presenting any symptoms].
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Aged↗
Structure-activity relationships of calcicludine and dendrotoxin-I, homologous peptides acting on different targets, calcium and potassium channels.
Calcicludine (CaC) and dendrotoxin-I (DTX-I) possess high homology of their primary structures despite their different biological activities acting on calcium and potassium channels, respectively. In order to elucidate the channel specificity displayed by these toxins, their three-dimensional structures were compared by NMR. These analyses revealed that their overall conformations are similar except for the structure at the N-terminus. To demonstrate the significance of this N-terminal, chimeric peptides, CaC(1-30)/DTX-I(31-60) and DTX-I(1-30)/CaC(31-60), were synthesized. The CD spectra and receptor-binding measurements of chimeric peptides indicated that the contribution to the overall conformation and to the affinity of the N-terminal part of molecule seem to be more important than that of the C-terminal one. These results suggest that the N-terminal part may participate in distinguishing between calcium and potassium channels.
Amino Acid Sequence↗
C/EBPbeta and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: implication for C/EBPbeta activity in eosinophil gene expression.
Eosinophil granule major basic protein (MBP) is expressed exclusively in eosinophils and basophils in hematopoietic cells. In our previous study, we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP (CCAAT/enhancer-binding protein) consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the cell line HT93A, which is capable of differentiating towards both the eosinophil and neutrophil lineages in response to retinoic acid (RA), C/EBPalpha mRNA expression decreased significantly concomitant with eosinophilic and neutrophilic differentiation, whereas C/EBPbeta expression was markedly increased. Electrophoretic mobility shift assays (EMSAs) showed that recombinant C/EBPbeta protein could bind to the potential C/EBP-binding site (bp -90 to -82) in the MBP promoter. Furthermore, we have demonstrated that both C/EBPbeta and GATA-1 can bind simultaneously to the C/EBP- and GATA-binding sites in the MBP promoter. To determine the functionality of both the C/EBP- and GATA-binding sites, we analyzed whether C/EBPbeta and GATA-1 can stimulate the MBP promoter in the C/EBPbeta and GATA-1 negative Jurkat T-cell line. Cotransfection with C/EBPbeta and GATA-1 expression vectors produced a 5-fold increase compared with cotransfection with the C/EBPbeta or GATA-1 expression vectors individually. In addition, GST pull-down experiments demonstrated a physical interaction between human GATA-1 and C/EBPbeta. Expression of FOG (riend ATA), which binds to GATA-1 and acts as a cofactor for GATA-binding proteins, decreased transactivation activity of GATA-1 for the MBP promoter in a dose-dependent manner. Our results provide the first evidence that both GATA-1 and C/EBPbeta synergistically transactivate the promoter of an eosinophil-specific granule protein gene and that FOG may act as a negative cofactor for the eosinophil lineage, unlike its positively regulatory function for the erythroid and megakaryocyte lineages.
Base Sequence↗
Critical role of sulfenic acid formation of thiols in the inactivation of glyceraldehyde-3-phosphate dehydrogenase by nitric oxide.
The relationship between possible modifications of the thiol groups of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by nitric oxide (NO) and modified enzyme activity was examined. There are 16 free thiols, including 4 active site thiols, in a tetramer of GAPDH molecule. NO donors, sodium nitroprusside (SNP), and S-nitroso-N-acetyl-DL-penicillamine (SNAP) decreased the number of free thiols with a concomitant inhibition of GAPDH activity in a concentration- and time-dependent manner. After treatment for 30 min, free thiols were maximally decreased to 8-10 per GAPDH tetramer and enzyme activity was also inhibited to 5-10% of control activity. In the presence of 30 mM dithiothreitol (DTT), these effects were completely blocked. Since similar results were obtained in the case of hydrogen peroxide (H2O2) treatment, which is known to oxidize the thiols, these effects of nitric oxide donors were probably due to modification of thiol groups present in a GAPDH molecule. On the other hand, DTT posttreatment after the treatment of GAPDH with SNP, SNAP, or H2O2 did not completely restore the modified thiols and the inhibited enzyme activity. DTT posttreatment after the 30-min-treatment with these agents restored free thiols to 14 in all treatments. In the case of SNAP treatment, all 4 active sites were restored and enzyme activity reached more than 80% of the control activity, but in two other cases one active site remained modified and enzyme activity was restored to about only 20%. Therefore, all 4 free thiols in the active site seem to be very important for full enzyme activity. DTT posttreatment in the presence of sodium arsenite, which is known to reduce sulfenic acid to thiol, almost completely restored both thiol groups and enzyme activity. These findings suggest that nitric oxide inhibits GAPDH activity by modifications of the thiols which are essential for this activity, and that the modification includes formation of sulfenic acid, which is not restored by DTT. S-nitrosylation, which is one type of thiol modification by NO, occurred when GAPDH was treated with SNAP but not SNP. Analysis of thiol modification showed that SNAP preferentially nitrosylated the active site thiols, the nitrosylation of which fully disappeared by DTT posttreatment. It seems that SNAP nitrosylates the active site thiols of GAPDH to prevent these thiols from oxidizing to sulfenic acid.
Binding Sites↗
Origin and phylogenetic distribution of Alu DNA repeats: irreversible events in the evolution of primates.
Over the past 60 million years, or so, approximately one million copies of Alu DNA repeats have accumulated in the genome of primates, in what appears to be an ongoing process. We determined the phylogenetic distribution of specific Alu (and other) DNA repeats in the genome of several primates: human, chimpanzee, gorilla, orangutan, baboon, rhesus, and macaque. At the population level studied, the majority of the repeats was found to be fixed in the primate species. Our data suggest that new Alu elements arise in unique, irreversible events, in a mechanism that seems to preclude precise excision and loss. The same insertions did not arise independently in two species. Once inserted and genetically fixed, the DNA elements are retained in all descendant lineages. The irreversible expansion of Alu s introduces a vector of time into the evolutionary process, and provides realistic (rather than statistical) answers to questions on phylogenies. In contrast to point mutations, the present distribution of individual Alu s is congruent with just one phylogeny. We submit that only irreversible and taxonomically relevant events are at the molecular basis of evolution. Most point mutations do not belong to this category.
Alu Elements↗
Molecular cloning of cDNA encoding human Rab3D whose expression is upregulated with myeloid differentiation.
To identify genes expressed in myeloid differentiation, we isolated a cDNA fragment by differential display using RNA prepared from HT93A cells, a human cell line capable of differentiating into neutrophil and eosinophil lineages in response to retinoic acid (RA). Evaluation of the full-length clone isolated from an HT93A cDNA library showed that it encoded a 24 kDa protein comprised of several domains conserved in the Ras superfamily. Comparison of the deduced amino acid sequence of this clone with Rab proteins revealed that it had highest homology to a small GTP-binding protein, murine Rab3D. The mRNA expression of human Rab3D was upregulated in the course of myeloid differentiation, and it was preferentially expressed in granulocytes. These results suggest that human Rab3D may play a specific role in granulocytes, for example in exocytosis of neutrophil-specific granules or in degranulation of both eosinophils and basophils.
Amino Acid Sequence↗
Tyrosine kinase involvement in apamin-sensitive inhibitory responses of rat distal colon.
1. It has been suggested that pituitary adenylate cyclase activating peptide (PACAP) may be involved in the non-adrenergic, non-cholinergic (NANC) inhibitory response of longitudinal muscle of rat distal colon. In this study, we have investigated the intracellular mechanism of PACAP-induced relaxation in this muscle. 2. PACAP induced an apamin-sensitive relaxation of the longitudinal muscle. The tyrosine kinase inhibitors genistein at 10 microM and tyrphostin 25 at 30 microM, but not the cyclic AMP-dependent protein kinase inhibitor Rp-8-bromoadenosine-3',5'-cyclic monophosphorothioate at 30 microM significantly inhibited the PACAP-induced relaxation to 60% and 25% of control values, respectively. PACAP did not increase the cyclic AMP content of the muscle. 3. Tyrphostin 25 at 10 microM significantly inhibited the relaxation of longitudinal muscle induced by electrical field stimulation (EFS), to 50% of control values. Apamin at 1 microM, an antagonist of small conductance Ca2+-activated K+ channels, also inhibited the relaxation, to 42 % of control values. The inhibitory effects of tyrphostin 25 and apamin were not additive (44 % of control values). 4. PACAP induced an apamin-sensitive, slow hyperpolarization of the cell membrane of the muscle. Tyrphostin 25 at 3 microM inhibited this PACAP-induced hyperpolarization. Tyrphostin 25 at 10 microM and genistein at 10 microM inhibited the apamin-sensitive inhibitory junction potentials induced by a single pulse of EFS. 5. The PACAP-induced relaxation of longitudinal muscle occurred with a concomitant decrease in intracellular Ca2+ levels ([Ca2+]i). Tyrphostin 25 at 10 microM and apamin at 1 microM abolished these PACAP-induced responses. 6. From these findings it is suggested that the activation of tyrosine kinase is involved in PACAP-induced relaxation of longitudinal muscle from rat distal colon, 'upstream of' the activation of apamin-sensitive K+ channels.
8-Bromo Cyclic Adenosine Monophosphate↗
Itai-itai disease is not associated with polymorphisms of the estrogen receptor alpha gene.
Itai-itai (or ouch-ouch) disease is a syndrome accompanied by bone mineral disorders, and which may be related to oral cadmium exposure. Itai-itai predominantly affects postmenopausal women with a history of multiple childbirths. Recently, it has been reported that polymorphisms of the estrogen receptor alpha (ERalpha) gene are associated with postmenopausal reduction of bone mineral density in Japanese women. However, estrogen receptors have never been studied in itai-itai disease. In this study, we examined the genotypic distributions of PvuII and XbaI restriction fragment length polymorphisms (RFLPs) of the ERalpha gene in patients with itai-itai disease and compared them with those of control subjects. The RFLPs are represented here as Pp (PvuII) and Xx (XbaI); the capital and small letters signify the absence and presence of restriction sites, respectively. The genotypic distributions of the patient group were: PP, 14.8%; Pp, 55.6%; pp, 29.6%; XX, 7.4%; Xx, 29.6%; and xx, 63.0%. These distributions were similar to those observed for the control groups, hence no pattern of genotypic distribution was observed that could be related to itai-itai disease. We conclude that RFLPs of the ERalpha gene may not be associated with itai-itai disease.
Adult↗
High incidence of a survival motor neuron gene/cBCD541 gene ratio of 2 in Japanese parents of spinal muscular atrophy patients: a characteristic background of spinal muscular atrophy in Japan?
Most spinal muscular atrophy (SMA) patients lack the survival motor neuron gene (SMN). However, the patients retain at least one copy of the cBCD541 gene (BCD), which is highly homologous with SMN. Here, we determined the SMN/BCD copy number ratios (the S/B ratios) of 12 parents of Japanese SMA patients with a homozygous SMN deletion, using competitive oligonucleotide priming polymerase chain reaction. We identified an S/B ratio of 2 in 25% of the parents examined, whereas less than 2% of parents of SMA patients in Western populations have an S/B ratio of 2. The high incidence of an S/B ratio of 2 in Japanese parents of SMA patients may reflect the characteristic genetic background of SMA in Japan.
Female↗