Endoscopic management of colocutaneous fistula after percutaneous endoscopic gastrostomy.
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Colonic Diseases↗
Biomedical subjects
D K Lee
Publications and source records attributed to D K Lee.
Induction of G(2)/M phase arrest and apoptosis by a new synthetic anti-cancer agent, DW2282, in promyelocytic leukemia (HL-60) cells.
We studied the effect of DW2282-,[(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl)-indoline-5-sulfonyl-4,5-dihydro-2-imidazolone].hydrochloride], a newly developed anti-cancer agent, on cell proliferation, cell cycle progression, and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. DW2282, a diarylsulfonylurea compound, was cytotoxic to HL-60 cells, with an IC(50) of 1.0 microg/mL. Treatment with DW2282 fragmented DNA in a concentration- and time-dependent manner, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that DW2282-treated HL-60 cells were hypodiploid, in terms of DNA content, and were arrested at the G(2)/M phase. The cell cycle arrest was reversible upon the removal of DW2282. HL-60 cells also underwent distinct morphological changes in response to DW2282 treatment, including the appearance of elongated cells with conical tails and other apoptotic characteristics. G(2)/M phase cell cycle arrest was accompanied by a decrease in the levels of cdc2, a protein that plays a critical role for progression through the G(2)/M phase. Treatment of HL-60 cells with DW2282 was also associated with decreased levels of the anti-apoptotic protein Bcl-2, activation of caspase-3, and proteolytic cleavage of poly(ADP-ribose) polymerase. Taken together, these results demonstrate that DW2282 dramatically suppressed HL-60 cell growth by inducing apoptosis after G(2)/M phase arrest. These findings are consistent with the possibility that G(2)/M phase arrest was mediated by the down-regulation of cdc2 levels in HL-60 cells. The data also suggest that DW2282 triggered apoptosis by decreasing Bcl-2 levels and activating caspase-3 protease. These results provide important new information towards understanding the mechanisms by which DW2282 and other diarylsulfonylureas mediate their therapeutic effects.
Antineoplastic Agents↗
Discovery and mapping of ten novel G protein-coupled receptor genes.
We report the identification, cloning and tissue distributions of ten novel human genes encoding G protein-coupled receptors (GPCRs) GPR78, GPR80, GPR81, GPR82, GPR93, GPR94, GPR95, GPR101, GPR102, GPR103 and a pseudogene, psi GPR79. Each novel orphan GPCR (oGPCR) gene was discovered using customized searches of the GenBank high-throughput genomic sequences database with previously known GPCR-encoding sequences. The expressed genes can now be used in assays to determine endogenous and pharmacological ligands. GPR78 shared highest identity with the oGPCR gene GPR26 (56% identity in the transmembrane (TM) regions). psi GPR79 shared highest sequence identity with the P2Y(2) gene and contained a frame-shift truncating the encoded receptor in TM5, demonstrating a pseudogene. GPR80 shared highest identity with the P2Y(1) gene (45% in the TM regions), while GPR81, GPR82 and GPR93 shared TM identities with the oGPCR genes HM74 (70%), GPR17 (30%) and P2Y(5) (40%), respectively. Two other novel GPCR genes, GPR94 and GPR95, encoded a subfamily with the genes encoding the UDP-glucose and P2Y(12) receptors (sharing >50% identities in the TM regions). GPR101 demonstrated only distant identities with other GPCR genes and GPR102 shared identities with GPR57, GPR58 and PNR (35-42% in the TM regions). GPR103 shared identities with the neuropeptide FF 2, neuropeptide Y2 and galanin GalR1 receptors (34-38% in the TM regions). Northern analyses revealed GPR78 mRNA expression in the pituitary and placenta and GPR81 expression in the pituitary. A search of the GenBank databases with the GPR82 sequence retrieved an identical sequence in an expressed sequence tag (EST) partially encoding GPR82 from human colonic tissue. The GPR93 sequence retrieved an identical, human EST sequence from human primary tonsil B-cells and an EST partially encoding mouse GPR93 from small intestinal tissue. GPR94 was expressed in the frontal cortex, caudate putamen and thalamus of brain while GPR95 was expressed in the human prostate and rat stomach and fetal tissues. GPR101 revealed mRNA transcripts in caudate putamen and hypothalamus. GPR103 mRNA signals were detected in the cortex, pituitary, thalamus, hypothalamus, basal forebrain, midbrain and pons.
Amino Acid Sequence↗
An experimental strategy to dramatically reduce the RF power used in cross polarization solid-state NMR spectroscopy.
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Journal Article↗
Solid-state (13)C NMR chemical shift anisotropy tensors of polypeptides.
Carbon-13 chemical shift anisotropy (CSA) tensors for various carbon sites of polypeptides, and for carbon sites in alpha-helical and beta-sheet conformations of poly-L-alanine, and polyglycine, are presented. The carbonyl (13)C CSA tensors were determined from one-dimensional CPMAS spectra obtained at a slow spinning speed, whereas the CSA tensors of C(alpha) and other carbons in side chains of peptides were determined using 2D PASS experiments on powder samples. The results suggest that the spans of (13)Carbonyl CSA tensors of alanine and glycine residues in various peptides are similar, even though the magnitude of individual components of the CSA tensor and the isotropic chemical shift are different. In addition, the delta(22) element is the only component of the (13)Carbonyl CSA tensor that significantly depends on the CO.HN hydrogen-bond length. Solid-state NMR experimental results also suggest that (13)Carbonyl and (13)C(alpha) CSA tensors are similar for alpha-helical and beta-sheet conformations of poly-L-alanine, which is in agreement with the reported quantum chemical calculation studies and previous solid-state NMR experimental studies on other systems. On the other hand, the (13)C(alpha) CSA tensor of the first alanine residue is entirely different from that of the second or later alanine residues of the peptide. While no clear trends in terms of the span and the anisotropic parameter were predicted for (13)C(beta) CSA tensors of alanine, they mainly depend on the conformation and dynamics of the side chain as well as on the packing interactions in the solid state of peptides.
Amino Acids↗
Large-fiber neuropathy in distal sensory neuropathy with normal routine nerve conduction.
Near-nerve needle sensory nerve conduction of plantar nerves in 100 patients with distal sensory neuropathy with normal routine nerve conduction (DSN-NNC) found the definite neuropathy pattern (abnormality in more than three of six tested nerves) in 65%, axonal neuropathy in 35%, and the known cause in 37% of patients. Absent or diminished reflexes were a reliable indicator for large fiber neuropathy (LFN). This near-nerve needle plantar nerve study provides useful and unequivocal evidence of its value in identifying neuropathy in DSN-NNC by finding LFN in 65% of patients.
Action Potentials↗
The transcription factors MTF-1 and USF1 cooperate to regulate mouse metallothionein-I expression in response to the essential metal zinc in visceral endoderm cells during early development.
During early development of the mouse embryo, expression of the metallothionein-I (MT-I) gene is heightened specifically in the endoderm cells of the visceral yolk sac. The mechanisms of regulation of this cell-specific pattern of expression of metallothionein-I are unknown. However, it has recently been shown that MTF-1, functioning as a metalloregulatory transcription factor, activates metallothionein genes in response to the essential metal zinc. In contrast with the metallothionein genes, MTF-1 is essential for development; null mutant embryos die due to liver degeneration. We report here that MTF-1 is absolutely essential for upregulation of MT-I gene expression in visceral endoderm cells and that optimal expression also involves interactions of the basic helix-loop-helix upstream stimulatory factor-1 (USF1) with an E-box1-containing sequence at -223 bp in the MT-I promoter. Expression of MT-I in visceral endoderm cells was dependent on maternal dietary zinc. Thus, the essential metal, zinc, apparently provides the signaling ligand that activates cell-specific MT-I expression in visceral endoderm cells.
Alkaline Phosphatase↗
Posttranscriptional regulation of human ADH5/FDH and Myf6 gene expression by upstream AUG codons.
Upstream open-reading frames are unusual in mammalian mRNAs. The 5' untranslated region of ADH5 mRNA contains an upstream open-reading frame (uORF) with two possible AUG start codons. Myf6 mRNA contains three tandem AUG repeats at the translation start site, a rare feature. Mutation at one or both of the upstream AUG codons in the ADH5 mRNA increased gene expression twofold in CV-1, NIH/3T3, HeLa, and SL2 cells. Mutation of these AUG codons led to 3- to 5-fold increases in activity as measured by in vitro translation assays using capped mRNAs. RNA toeprint analysis demonstrated many stalled ribosomes flanking the AUG codons and secondary structures near the AUGs. Secondary structures may increase the ability of ribosomes to recognize the two AUGs, despite their poor initiation context. The degree of repression by uAUGs varied significantly depending on the cell lines tested, which may partly explain the differential tissue expression. Myf6 is a critical myogenic transcription factor with the striking feature of three tandem AUG codons at the translation initiation site. This structure reduced expression; removing two of these AUGs led to a doubling of activity in CV-1, HeLa, and NIH/3T3 cells.
3T3 Cells↗
The hepatitis B virus encoded oncoprotein pX amplifies TGF-beta family signaling through direct interaction with Smad4: potential mechanism of hepatitis B virus-induced liver fibrosis.
Hepatitis B, one of the most common infectious diseases in the world, is closely associated with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Many clinical investigations have revealed that hepatic fibrosis is an important component of these liver diseases caused by chronic hepatitis B. TGF-beta signaling plays an important role in the pathogenesis of fibrosis in chronic hepatitis and cirrhosis. As these diseases are associated with hepatitis B virus (HBV) infection, we examined the possibility that the HBV-encoded pX oncoprotein regulates TGF-beta signaling. We show that pX enhances transcriptional activity in response to TGF-beta, BMP-2, and activin by stabilizing the complex of Smad4 with components of the basic transcriptional machinery. Additionally, confocal microscopic studies suggest that pX facilitates and potentiates the nuclear translocation of Smads, further enhancing TGF-beta signaling. Our studies suggest a new paradigm for amplification of Smad-mediated signaling by an oncoprotein and suggest that enhanced Smad-mediated signaling may contribute to HBV-associated liver fibrosis.
3T3 Cells↗
Identification of four novel human G protein-coupled receptors expressed in the brain.
We report the discovery and tissue distributions of four novel human genes, GPR61, GPR62, GPR63 and GPR77, all of which encode G protein-coupled receptors (GPCRs). GPR61 was discovered in a search of the patent literature which retrieved a rabbit DNA sequence partially encoding a novel GPCR. This sequence was used to obtain a full-length human cDNA encoding GPR61, a receptor of 417 amino acid length. A search of the GenBank genomic sequence databases revealed three previously unrecognized intronless genes encoding the orphan GPCrs (oGPCRs) GPR62, GPR63 and GPR77, with respective amino acid lengths of 368, 419 and 337. Sequence analysis revealed that GPR61 and GPR62, and a published orphan receptor p47MNR, shared the highest level of identities to each other, ranging from 36 to 45% in the transmembrane (TM) domains. Together, these three oGPCRs appear to comprise a novel subfamily of GPCRs, most closely related to the serotonin 5-HT(6) receptor. Sequence analysis of GPR63 and GPR77 revealed highest sequence identities in the TM regions with the oGPCR PSP24 (58%) and the anaphylatoxin C5a receptor (49%) respectively. Tissue distribution analyses detected the expression of all four novel genes in the human brain. GPR61 mRNA expression was detected in the caudate, putamen and thalamus of human brain, with a more widespread expression pattern in rat brain, with mRNA signals in areas of the cortex, hippocampus, thalamus, hypothalamus and midbrain. GPR62 mRNA expression was detected in the basal forebrain, frontal cortex, caudate, putamen, thalamus and hippocampus. GPR63 mRNA expression was detected in the frontal cortex, with lower levels in the thalamus, caudate, hypothalamus and midbrain. Analysis of GPR77 mRNA expression revealed signals in the frontal cortex, hippocampus and hypothalamus with high transcript levels in the liver.
Animals↗
Comparison of the efficacy and safety of different formulations of omeprazole-based triple therapies in the treatment of Helicobacter pylori-positive peptic ulcer.
Little is known about the efficacy and safety of different formulations of omeprazole-based triple therapy regimens for the treatment of Helicobacter pylori-positive peptic ulcer. We compared the efficacy and safety of two formulations of omeprazole used in triple therapies in patients with H. pylori-positive active peptic ulcer. Seventy-four patients with endoscopically proven H. pylori-positive active peptic ulcer were randomized to two groups, each with 37 patients, to receive either OAC-I (6 weeks of "A" formulation of omeprazole [20 mg twice daily] plus 2 weeks of amoxicillin [1.0 g twice daily] and clarithromycin [500 mg twice daily] or OAC-II (6 weeks of "B" formulation of omeprazole [20 mg twice daily] plus 2 weeks of the same antibiotics. The H. pylori and ulcer healing status were assessed at the baseline and at the 6-week endpoint of therapy. Gastrointestinal symptoms, documentation of adverse events, and standard laboratory examinations were assessed at each visit. Eradication of H. pylori (intention to treat [n = 74]/per protocol [n = 66]) and healing of the ulcer were successful in 83.8%/96.9% and 93.8%, respectively, of the OAC-I group patients, and in 91.9%/100% and 97.1%, respectively, of the OAC-II group patients (P = 0.477; P = 0.608). The OAC-I group experienced rapid resolution of symptoms, but no significant differences were found between the two groups for number of days taken for resolution of gastrointestinal symptoms, adverse events, and laboratory findings. The two different formulations of omeprazole used in triple therapy regimens produced similar efficacy and safety results after 6 weeks of treatment in patients with H. pylori-positive active peptic ulcer.
Adult↗
DNA bending by asymmetrically tethered cations: influence of tether flexibility.
BACKGROUND: We have been studying the proposal that laterally asymmetric charge neutralization along the DNA double helix can induce collapse toward the neutralized surface. Results of previous experiments implied that such a phenomenon can occur, suggesting a role for local interphosphate repulsive forces in DNA shape and rigidity. RESULTS: We now show that, whereas six ammonium ions tethered to one DNA face on flexible propyl chains can induce detectable DNA curvature, tethering of ammonium ions on rigid propynyl tethers does not induce DNA curvature. Molecular modeling indicates differing propensities for phosphate salt bridge formation between propyl- and propynyl-tethered ammonium ions. CONCLUSIONS: Ammonium ion localization is suggested as a key factor in induced bending. Rigidification of the double helix by stacking of propyne groups cannot be excluded.
Cations↗
Orphan G protein-coupled receptors in the CNS.
The majority of genes encoding G protein-coupled receptors were isolated by methods based on sequence similarities found throughout this family. Experimental techniques have exploited these similarities (including low-stringency hybridization, polymerase chain reaction and electronic database searching) to identify genes encoding many pharmacologically recognized receptors and their subtypes. Homology-based searches have revealed receptors for which the endogenous ligands were unknown and these were named orphan receptors. Many orphan receptors are expressed in the brain, suggesting the existence of unidentified neurotransmitters. Methods used to identify ligands for these orphan receptors resulted in the identification of novel ligands and succeeded in pairing previously identified ligands with their receptors. Similar successful strategies are required to characterize the physiological and pathological importance of the remaining orphan receptors to facilitate the discovery of novel drugs for these systems.
Animals↗
Determination of binding constant of transcription factor AP-1 and DNA. Application of inhibitors.
The equilibrium binding and association kinetics of the fos-jun dimer (basic and leucine zipper domain) to the AP-1 DNA were studied using a quantitative assay. The basic-region and leucine zipper (bZip) domain of c-fos was expressed as a fusion protein with glutathione S-transferase, and it was bound to glutathione-agarose. The GST-fused fos bZip region was allowed to form a heterodimer with the bZip domain of c-jun, to which radiolabeled AP-1 nucleotides were added. After thorough washing, the gel-bound radioactivity was counted. The binding and dissociation rate constants (k(1) and k-(1)) of the fos-jun dimer and DNA could be obtained from a time-course experiment. The association binding constant (K(1)) was determined using both a thermodynamic equation and kinetic parameters. Nordihydroguaiaretic acid (NDGA), momordin I, natural product inhibitors of the fos-jun/DNA complex formation, was applied to this jun-GST-fused fos system and it was found to decrease the apparent equilibrium binding of dimer and DNA. The thermodynamic constant of dimer and inhibitor binding was also determined.
Cloning, Molecular↗
The role of endoscopic retrograde pancreatography in the treatment of traumatic pancreatic duct injury.
BACKGROUND: The status of the main pancreatic duct (MPD) is the most important determinant of the morbidity and mortality associated with pancreatic trauma. Early diagnosis and optimal treatment are critical, especially when there is MPD injury. METHODS: Twenty-three patients with pancreatic trauma were studied prospectively with respect to clinical and laboratory findings, CT, and endoscopic retrograde pancreatography (ERP). Treatment modalities and clinical outcome were assessed in relation to ERP findings. RESULTS: The pancreatic duct was injured in 14 of 23 patients (11 MPD, 3 branch duct). Contrast leakage from the MPD into peritoneal cavity at ERP confirmed MPD injury in 8 patients, who underwent surgical exploration. Three patients with leakage from a branch duct into the pancreatic parenchyma recovered with conservative treatment. Three patients in whom ERP demonstrated contrast leakage from the MPD confined to the parenchyma underwent successful transpapillary stent insertion with complete resolution of the leak at 3-month follow-up. Patients who underwent ERP more than 72 hours after trauma had a significantly higher rate of pancreas-associated complications and a tendency to remain hospitalized longer than patients who underwent ERP earlier. CONCLUSION: Early ERP is one of the most useful methods for demonstrating MPD injury. ERP assists with treatment planning based on the degree of pancreatic duct injury.
Abdominal Injuries↗
Ileal vasculitis in Henoch-Schönlein purpura.
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Adult↗
Innervation of the lower eyelid in relation to blepharoplasty and midface lift: clinical observation and cadaveric study.
Ectropion or scleral show resulting from weakness of the lower eyelids is not uncommon after lower blepharoplasty or midface lift via blepharoplasty incision. Denervation of the pretarsal orbicularis oculi muscle (OOM) attributes to such complications. The authors analyzed 102 patients who underwent midface lift via lower blepharoplasty incision for the past 3 years and investigated the motor nerve innervation of the lower OOM in 20 cadavers. They encountered two cases of ectropion attributed to the denervation of the pretarsal OOM: one with dry-eye syndrome and scleral show, and the other with a "polar bear-like appearance" (i.e., outer eversion of the lower eyelid). All pretarsal and preseptal OOMs were innervated by five to seven terminal twigs of the zygomatic branches of the facial nerve that approached the muscle at a right angle. The medial portion of the lower OOM was innervated by one to two terminal twigs of the buccal branch, and the middle portion was innervated with two to three twigs of the zygomatic branch. The lateral portion was supplied by the uppermost zygomatic branch, which split into two to four twigs. The mean horizontal distance between the lateral canthus and the zygomatic branch was 2.31 +/- 0.29 cm (range, 1.7-2.7 cm) and the vertical distance was 1.20 +/- 0.20 cm (range, 0.8-1.5 cm). The critical zone was a circle with 0.5-cm radius, and its center was located 2.5 cm inferolaterally (30 deg) from the lateral canthus. It is very important to understand the motor nerve innervation of the lower eyelid and the "critical zone" to avoid postoperative ectropion or weakness of the lower eyelid resulting from paralysis of the pretarsal or preseptal OOM.
Blepharoplasty↗
Patterns of oculomotor nerve distribution to the levator palpebrae superioris muscle, and correlation to temporary ptosis after blepharoplasty.
Transient diplopia, blepharoptosis, or both conditions are rare postoperative complications of blepharoplasty performed with the patient under local anesthesia. It has been hypothesized that some cases of postoperative diplopia and blepharoptosis could be attributed to the myotoxic effects of local anesthetics to the extraocular muscles and the levator muscle or to the neurotoxic effects of lidocaine. In 30 cadavers, the superior division of the oculomotor nerve was severed en bloc 1.5 cm anterior to the annulus of Zinn with the levator palpebrae superioris (LPS) and the superior rectus muscles. These muscles were detached from their origins, and their attachments to the scleral and tarsal plates were divided respectively. The specimens were treated in guanidine-hydrochloride and Alizarin Red solution, and were dissected under an operating microscope. The nerve branches of the superior division of the oculomotor nerve innervated the proximal third (type I) in 2 of 30 LPS muscles (6.7%), in 8 of 30 muscles (26.7%) extended to the middle third (type II), and reached the distal third (type III) in 20 of 30 muscles (66.7%). The terminal branches ran through the medial third (type IIIa) in 6 of 20 type III LPS muscles (30%), the central third (type IIIb) in 8 muscles(40%), and the lateral third (type IIIc) in 6 muscles (30%). The oculomotor nerve ends that extend forward to the distal third of the LPS muscle (type III) are exposed and vulnerable to local anesthetics and may be numbed during blepharoplasty. If this is so, postoperative blepharoptosis may be caused by transient paralysis of the LPS muscle, and great care should be taken during the injection of local anesthetics near the LPS.
Anesthetics, Local↗