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Biomedical subjects

D K Lee

Publications and source records attributed to D K Lee.

At least 37 records · Page 2Linked to original sources

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↗

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↗

Le Fort I osteotomy with sparing fracture of lateral pterygoid plate.

This study aimed to clarify the relation between the anatomical variations of the pterygomaxillary region and fracture of the pterygoid plate during Le Fort I osteotomy. We present a secure method to separate maxillary tuberosities from pterygoid plates without injuring the pterygoid plates. Thirty specimens of hemisection of Korean skulls were used for the study. The maxilla was sectioned transversely on the floor of the pyriform aperture and posteriorly to the lateral pterygoid plate with a mechanical saw. The section was 5 to 6 mm above the tooth roots. The pterygomaxillary junction was separated with a curved osteotome in two steps: initially with light tapping of the shallow groove 2 to 3 mm anterior to the pterygomaxillary fissure at a half right angle and then changing the course of forceful tapping to more than 60 degrees. The maxillary tuberosity separated from the medial and lateral pterygoid plates during the procedure was grouped into the "disjunction group" (24 of 30, 80%) and the pterygoid plates fractured were grouped into the "fracture group" (6 of 30, 20%). The thickness of the pterygomaxillary region (T) was significantly greater in the disjunction group than in the fracture group (P = 0.034). The concavity of the pterygomaxillary fissure (C) was significantly deeper in the disjunction group than in the fracture group (P = 0.020). There was no significant difference of width of the pterygomaxillary fissure between the disjunction group and the fracture group (P = 0.169). The thin pterygomaxillary region and less concave pterygomaxillary fissure on the preoperative computed tomography scan draw precautionary attention to vulnerable pterygoid plates fractured in the procedure of Le Fort I osteotomy.

Adult↗

Discovery of a novel member of the histamine receptor family.

We report the discovery, tissue distribution and pharmacological characterization of a novel receptor, which we have named H4. Like the three histamine receptors reported previously (H1, H2, and H3), the H4 receptor is a G protein-coupled receptor and is most closely related to the H3 receptor, sharing 58% identity in the transmembrane regions. The gene encoding the H4 receptor was discovered initially in a search of the GenBank databases as sequence fragments retrieved in a partially sequenced human genomic contig mapped to chromosome 18. These sequences were used to retrieve a partial cDNA clone and, in combination with genomic fragments, were used to determine the full-length open reading frame of 390 amino acids. Northern analysis revealed a 3.0-kb transcript in rat testis and intestine. Radioligand binding studies indicated that the H4 receptor has a unique pharmacology and binds [(3)H]histamine (K(d) = 44 nM) and [(3)H]pyrilamine (K(d) = 32 nM) and several psychoactive compounds (amitriptyline, chlorpromazine, cyproheptadine, mianserin) with moderate affinity (K(i) range of 33-750 nM). Additionally, histamine induced a rapid internalization of HA-tagged H4 receptors in transfected human embryonic kidney 293 cells.

Amino Acid Sequence↗

Chordoid meningioma with polyclonal gammopathy. Case report.

The authors present a case of chordoid meningioma in a 55-year-old woman who manifested headache and personality change. Magnetic resonance imaging of the brain and cerebral angiography demonstrated a mass in the right frontal lobe that resembled a typical convexity meningioma. However, the pathological diagnosis was chordoid meningioma, a rare subtype of this tumor that usually occurs in adolescence and is known to be associated with Castleman syndrome. A meningothelial meningiomatous pattern suggestive of a meningothelial origin was focally present, and cytokeratin-positive squamoid cells were noted in the tumor. The lesion lacked dense infiltration of lymphocytes and plasma cells. Polyclonal gammopathy was the only sign of Castleman syndrome and hypochromic microcytic anemia was absent in this case. Polyclonal gammopathy resolved completely 6 months after total removal of the mass.

Castleman Disease↗

Postoperative spinal seeding of craniopharyngioma. Case report.

The authors present a case of postoperative spinal seeding of papillary craniopharyngioma. This 27-year-old man who had previously undergone subtotal removal of a suprasellar craniopharyngioma was admitted because of low-back and right leg pain. Results of neurological examination showed a limitation in straight-leg raising in the right side with no sensorimotor changes. Magnetic resonance imaging of the lumbar spine demonstrated multiple enhanced intradural extramedullary masses causing spinal cord compression. Pathological examination of the tumor tissue obtained via laminectomy revealed papillary craniopharyngioma, which had the same histological features as those of the previous suprasellar tumor. Several ectopic recurrences of craniopharyngioma have been reported; however, the authors believe that this is the first published report of the spinal seeding of craniopharyngioma.

Adult↗

Mechanism of induction of transforming growth factor-beta type II receptor gene expression by v-Src in murine myeloid cells.

Transforming growth factor (TGF)-beta1 plays an important role during hematopoiesis. Previously, we had shown that the growth of a v-Src-transformed myeloid cell line was markedly more inhibited by TGF-beta treatment when compared with the wild-type myeloid cell line. To investigate the increased growth sensitivity of the v-Src-transformed myeloid cell line, 32D-src, to TGF-beta, we examined expression of the TGF-beta type II receptor (TGF-beta RII) gene in myeloid cell lines. Northem blot analysis showed that expression of approximately 8- and 6-kb species of TGF-beta RII transcripts was markedly increased in the 32D-src cell line. The expression of the TGF-beta RII promoter linked to a reporter gene was increased 23-fold by v-Src. DNA transfection and electrophoretic mobility shift assay revealed that v-Src induces TGF-beta RII promoter activity through an AP1/ATF2-like sequence (-219 to -172), ETS binding sites (+1 to +36), and the inverted CCAAT box (-81 to -77). Novel DNA-protein complexes with ETS binding sites are significantly increased in v-src-transformed cell lines compared with the control cell line. These results suggest that v-Src induces activity of the TGF-beta RII promoter through multiple elements by inducing expression of nuclear proteins interacting with these elements.

Animals↗

Field evaluation of an insect growth regulator, pyriproxyfen, against Aedes togoi larvae in brackish water in South Korea.

The granular formulation of 0.5% pyriproxyfen was evaluated for inhibition of emergence of Aedes togoi in brackish water of rock pools near a coastal area in Pusan, South Korea. Complete adult emergence inhibition in 4th-stage larval and pupal isolations was affected from 5-40 days at 0.05 mg/l after treatment. Most inhibition rates were over 80% throughout the test period at all test concentrations of pyriproxyfen except 61.0% and 67.5% of inhibition rates at 0.01 mg/l at 52 days and 62 days after treatment, respectively. It is suggested that the dose for successive control of Ae. togoi for long-term might be 0.05-0.1 mg/l of 0.5% pyriproxyfen granules.

Aedes↗

Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation.

Androgen receptor (AR) may communicate with the general transcription machinery on the core promoter to exert its function as a transcriptional modulator. Our previous report demonstrated that the AR interacted with transcription factor IIH (TFIIH) under physiological conditions and that overexpression of Cdk-activating kinase, the kinase moiety of TFIIH, enhanced AR-mediated transcription in prostate cancer cells. In an effort to further dissect the mechanisms implicated in AR transactivation, we report here that AR interacts with PITALRE, a kinase subunit of positive elongation factor b (P-TEFb). Cotransfection of the plasmid encoding the mutant PITALRE (mtPITALRE), defective in its RNA polymerase II COOH-terminal domain (CTD)-kinase activity, resulted in preferential inhibition of AR-mediated transactivation. Indeed, AR transactivation in PC-3 cells was preferentially inhibited at the low concentration of 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB), a CTD kinase inhibitor. These results suggest that CTD phosphorylation may play an important role in AR-mediated transcription. Furthermore, a nuclear run-on transcription assay of the prostate-specific antigen gene, an androgen-inducible gene, showed that transcription efficiency of the distal region of the gene was enhanced upon androgen induction. Taken together, our reports suggest that AR interacts with TFIIH and P-TEFb and enhances the elongation stage of transcription.

Cell Line↗

Ion chromatography detector based on solid-state ion-selective electrode array.

A variety of neutral carrier type ionophores for monovalent cations were employed to prepare solid-state cation-selective electrodes (SSEs) for use as a detector in single-column ion chromatography (IC). The polyurethane-based pseudoreference electrode made it possible to assemble an array type SSE detector for IC. An SSE-based detector provides not only the overall chromatogram for the separated ion species (monensin methyl ester-nonactin-based membrane), but also the enhanced chromatogram for specified ions of interest (valinomycin as K+ and nonactin for NH4+). This feature makes it possible to perform highly quantitative analysis with low detection limits even if the separation efficiency of the ion-exchange is not sufficient. Since SSE-based IC detectors are easily miniaturized and replaceable at low cost, they are an ideal component of a portable IC system.

Cations, Monovalent↗

A planar pCO2 sensor with enhanced electrochemical properties.

To develop planar microchemical pCO2 sensing devices with improved electrochemical properties, we combined two advanced technologies. One is a differential sensor arrangement to simplify the microfabrication procedure by employing pH-sensitive gas-permeable membranes, and the other is the use of an enzyme (carbonic anhydrase) to shorten total measurement time by accelerating the rate of CO2 hydration. The adhesion of the polyurethane-matrix gas-permeable membrane is enhanced significantly by incorporating a silanizing reagent (silicon tetrachloride), improving the stability and extending sensor lifetime. The proposed differential pCO2 microelectrodes exhibited significantly improved performance in their preconditioning period, response and recovery times, stability, response slope, and lifetime.

Biosensing Techniques↗

5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists.

A series of 5-alkyltryptamines (6) and the corresponding conformationally constrained analogues (8) have been synthesized. The structure activity relationships (SAR) at the 5-position of the indole skeleton and the ethylamine side chain have been studied. Functional activities were assessed using isolated rabbit saphenous vein. Potent, selective ligands were found (6e, Ki 2.5 nM, 5-HT1B/5-HT1D 125-fold) that have potential for treating acute migraine.

Animals↗