Biomedical subjects

C H Kang

Publications and source records attributed to C H Kang.

At least 37 records · Page 2Linked to original sources

PubMed1997

A case of bronchiolitis obliterans organizing pneumonia associated with adenovirus.

A 58-year-old man described a short history of dyspnea and a preceding flu like illness with roentgenographic features of an interstitial lung disease. An open lung biopsy specimen from him showed bronchiolitis obliterans with organizing pneumonia (BOOP). Adenovirus was isolated from a throat swab. There was both clinical and radiographic improvement with supportive care. We herein report a first case of BOOP associated with adenovirus in Korea.

Adenoviridae↗

PubMed1996

A highly efficient 24-condition matrix for the crystallization of nucleic acid fragments.

A matrix screen is presented with optimized conditions for the crystallization of nucleic acid fragments. The screen consists of 24 conditions only and utilizes minimal amounts of sample. It has been tested on a series of DNA and RNA oligomers, and yielded diffraction-quality crystals of many specimens including drug-DNA complexes. Preliminary X-ray analysis of the crystals is reported.

Chemistry Techniques, Analytical↗

PubMed1996

Clinical features of interstitial lung diseases.

OBJECTIVES: Interstitial lung diseases (ILD) are heterogeneous groups of disorders that involve the interstitium of the lung. Lung biopsy is mandatory in most cases of ILD for diagnosis. In Korea, a few clinical data about ILD were analyzed on the basis of pathologic proof. Thus, we analysed the clinical profiles of patients with ILD who had lung biopsy in a tertiary university hospital. METHODS: Clinical and pathologic data concerning 100 patients who had open lung biopsy (OLB) and/or transbronchial lung biopsy (TBLB) were prospectively analysed. Two patients were excluded because one patient was proven to have metastatic cancer and the other to have miliary tuberculosis. One patient had two combined diseases: rheumatoid arthritis and pneumoconiosis. Thus, 99 cases were analysed from 98 patients. Demographic characteristics, pulmonary functions and pathologic findings were analysed according to the disease entities of ILD. Pathologic findings were classified only in patients who had OLB. Clinical courses were also analysed during follow-up. RESULTS: OLB was performed on 68 cases with concomittant TBLB in 18 cases and 30 cases had TBLB only. Mediastinal lymph node biopsy has performed on one case. The most common cause of ILD was IPF (51.5%), which was followed by CVD.PF (15.2%) and HP (9.1%). Average age of 51 cases with idiopathic pulmonary fibrosis (IPF) was 60 +/- 11 years, that of 15 cases with collagen vascular disease associated pulmonary fibrosis (CVD-PF) was 46 +/- 17 years and that of 9 cases with hypersensitivity pneumonitis (HP) was 53 +/- 8.1 years. In IPF, CVD-PF AND HP, male to female ratio was equal. But female was dominant in sarcoidosis and male was dominant in pneumoconiosis. Pulmonary function tests (PFT) in IPF, CVD-PF and HP were restrictive patterns in half of the cases. In pneumoconiosis and sarcoidosis, PFT showed normal pattern. Usual interstitial pneumonia (UIP) was the most common pathologic type in IPF and CVD-PF. The most common cause of CVD-PF was rheumatoid arthritis. The overall mortality rate was 12.1%. CONCLUSION: We reported that the ILD had a variety of disease entities and pathologic types even in one tertiary referral hospital. We hope that a multi-center study will be performed on the basis of pathologic proof in the future.

Adult↗

PubMed1996

Nonspecific interstitial pneumonia/fibrosis: clinical manifestations, histologic and radiologic features.

OBJECTIVES: Customarily used classification of IPF did not satisfy a sizable group of patients with IPF that in the past had been lumped with UIP and now currently has begun to be recognized as nonspecific interstitial pneumonia/fibrosis (NIP). There are few reports about the clinical features of NIP. METHODS: The pathologic slides of 66 patients having open lung biopsy (OLB) for the differential diagnosis of interstitial lung diseases (ILD) from 1984 to 1995 were reviewed. Seven cases were confirmed as NIP. The clinical record, pulmonary function tests (PFT), chest PA and HRCT were reviewed and analysed retrospectively. RESULTS: Six patients with NIP were female. The median age was 56 years. Mean duration of symptoms was 4 months. Five patients had systemic flu-like symptoms, the most common respiratory symptom was gradual dyspnea. Two patients revealed a mild degree of anemia. Four cases had leukocytois of more than 10,000/mm3. ESR and CRP O.K. elevated in all measured cases. Anti-nuclear antibody (ANA) was positive in three of six patients and ds-DNA antibody was positive in one of six patients. Restrictive pattern of PFT was predominant. Diffusion capacity of carbon monoxide (DLCO) decreased markedly. In bronchoalveolar lavage (BAL), total cell counts elevated about three times of normal value. On differential counts of BAL cells, lymphocytes, neutrophils and eosinophils were higher than those of normal controls. The prominent finding of chest radiology was bilaterally patchy opacifications in parenchyme of lower lung zones. On HRCT, bilaterally patchy areas of ground-glass attenuation and/or areas of alveolar consolidation were commonly shown. The number of pathologic type was one case of group I, four cases of group II and two cases of group III. The average period from diagnosis to the last follow-up was 24.8 months. Five patients were clinically recovered to the previously well-being state. CONCLUSION: Patients with NIP had different clinical features from UIP, AIP and DIP. They also had characteristic findings of radiology and their prognosis seems to be better than UIP.

Adult↗

PubMed1995

Erysodine, a competitive antagonist at neuronal nicotinic acetylcholine receptors.

Erysodine, an erythrina alkaloid related to dihydro-beta-erythroidine, was found to be a more potent inhibitor of [3H]cytisine binding at neuronal nicotinic acetylcholine receptors but a less potent inhibitor of [125I]alpha-bungarotoxin binding at muscle-type nicotinic acetylcholine receptors than dihydro-beta-erythroidine. Erysodine was a competitive, reversible antagonist of (-)-nicotine-induced dopamine release from striatal slices and inhibited (-)-nicotine-induced 86Rb+ efflux from IMR-32 cells. Erysodine was equipotent with dihydro-beta-erythroidine in the dopamine release assay but 10-fold more potent in the 86Rb+ efflux assay, suggesting differential subtype selectivity for these two antagonists. Erysodine, systemically administered to mice, entered the brain and significantly attentuated nicotine's hypothermic effects and its anxiolytic-like effects in the elevated plus-maze test. There was greater separation between antagonist and toxic doses for erysodine than for dihydro-beta-erythroidine, perhaps because of erysodine's greater selectivity for neuronal receptors. In rats, erysodine prevented both the early developing decrease and the late-developing increase in locomotor activity produced by (-)-nicotine. The potent and competitive nature of erysodine's antagonism together with its ability to enter the brain after systemic administration suggest that erysodine may be a useful tool in characterizing neuronal nicotinic acetylcholine receptors.

Alkaloids↗

PubMed1995

A case of amiodarone-associated pulmonary toxicity.

Amiodarone is an iodinated benzofuran derivative that represents a new and extremely effective therapy for certain life-threatening refractory cardiac arrgythmia. There are numerous side effects associated with amiodarone therapy, including corneal microdeposits. Skin reactions and others. Pulmonary toxicity, however, represents the most serious adverse reaction limiting the clinical effecacy of this antidysrhythmic drug. Recently, we experienced a case of amiodarone-induced pulmonary toxicity confirmed by open lung biopsy with light-and electron-microscopy. So, we report a case of amiodarone-induced pulmonary toxicity with a literature review.

Aged↗

PubMed1994

Crystal structure of intercalated four-stranded d(C3T) at 1.4 A resolution.

The crystal structure of d(C3T), solved at 1.4 A resolution, reveals that the molecule forms a four-stranded intercalated complex. It consists of two parallel-stranded duplexes, each of which is held together by cytosine-protonated cytosine base pairs. The two duplexes are intercalated with each other and have opposite strand orientation. The molecule has a flat, lath-like appearance, and the covalently bonded cytosines have a slow right-handed twist of 17.1 degrees. However, there is considerable asymmetry. On one of the flat sides, the phosphate groups are rotated away from the center of the molecule. They are held in this orientation by bridging water molecules that bind the NH of cytosine and a phosphate group of an opposite chain. There is also considerable microheterogeneity in the structure. The cytosine hemiprotonation occurs even at pH 7 where stable crystals form.

Crystallography, X-Ray↗

PubMed1994

The bacterial periplasmic histidine-binding protein. structure/function analysis of the ligand-binding site and comparison with related proteins.

Bacterial periplasmic binding proteins are initial receptors in the process of active transport across cell membranes and/or chemotaxis. Among them, the histidine-binding protein (HisJ) has been extensively studied from the biochemical, physiological, and genetic points of view. The three-dimensional crystal structure of the histidine-binding protein complexed with histidine has been determined at 2.5-A resolution by the molecular replacement method using a probe structure the previously solved lysine-liganded structure of the lysine-, arginine-, ornithine-binding protein (LAO), which shares 70% sequence identity with HisJ. The structure is bi-lobate; the two lobes, one bigger than the other, are connected by two short strands and are in contact with each other (closed) enclosing the histidine. Charged, polar, and non-polar side chains, as well as the peptide backbone, are involved in tight binding of the histidine. The bound histidine is involved in eight direct hydrogen bonds, six with the bigger lobe and two with the smaller lobe, in one potential water-mediated hydrogen bond with the bigger lobe, as well as in ionic interactions. The HisJ residues surrounding the ligand are the same as the LAO residues interacting with lysine, except for residue 52 which is leucine in HisJ and phenylalanine in LAO. The Leu-52 in HisJ makes a hydrophobic interaction with the imidazole ring of histidine. Of seven mutations affecting the ligand-binding site, five are located in the ligand-binding site, one in a connecting strand, and one at the domains interface. Based on comparisons among related binding proteins, the specific interactions between the ligands and the respective binding protein residues are predicted for the glutamine-binding protein and the opines-binding protein.

Bacterial Proteins↗

PubMed1994

A case of tetanus mimicking acute abdomen.

A 47-year-old man presented with backache and signs of acute abdomen. An exploratory laparotomy was performed. Post-operatively he developed hypoxaemia in the operating theatre and was brought to the Surgical Intensive Care Unit for ventilatory support and further investigations. History was then retaken and revealed a minor foot injury one month ago with subsequent development of muscle spasm and dysphagia. The diagnosis of tetanus was made. The patient was then treated with human antitetanus immune globulin and crystalline penicillin. Ventilatory support was continued, aided by infusion of morphine, diazepam and alcuronium. The recovery course was complicated by chest infection, urinary tract infection and sympathetic overactivity. He improved later and ventilatory support was discontinued three weeks after admission. He then made uneventful recovery and was discharged from the hospital forty days after admission.

Abdomen, Acute↗

PubMed1994

(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: II. In vivo characterization.

(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418), an isoxazole analog of (-)-nicotine, is a potent agonist at the alpha-4/beta-2 subtype of neuronal nicotinic acetylcholine receptor (nAChR) that exists in mammalian brain (Arneric et al., 1994). Compared to (-)-nicotine, ABT 418 has reduced potency to interact with the subunit isoforms of nAChR found in sympathetic ganglia, and it does not compete for alpha-bungarotoxin binding sites in brain or at the neuromuscular junction. ABT 418 [minimum effective dose (MED), 0.062 mumol/kg i.p.) was 10-fold more potent in improving retention of avoidance learning in normal mice than (-)-nicotine, whereas the (R)-enantiomer of ABT 418, A-81754, was inactive. The memory-enhancing effect of ABT 418 was prevented by the nAChR channel blocker, mecamylamine. In the elevated plus-maze model of anxiety, ABT 418 (MED, 0.19 mumol/kg i.p.) increased open-arm exploration in mice, as previously shown for (-)-nicotine (MED, 0.62 mumol/kg i.p.). A-81754, did not have anxiolytic-like effects in this test. Unlike the classical anxiolytic, diazepam, ABT 418 did not impair rotorod performance in the dose range where beneficial effects occurred. In rats, ABT 418 (MED, 0.002 mumol/kg i.v.) was remarkably potent in enhancing basal forebrain-elicited increases in cortical cerebral blood flow, whereas resting cerebral blood flow was unaffected. Free running cortical electroencephalography in rats was unaffected by ABT 418 at a dose of 1.9 mumol/kg i.p., whereas the same dose of (-)-nicotine caused cortical activation (decreased power in the 1-13 Hz range and increased power in the 25-50 Hz range). Whereas ABT 418 was approximately 3- to 10-fold more potent than (-)-nicotine in memory enhancement and anxiolytic test paradigms, the compound had less emetic liability in dogs as compared to (-)-nicotine, and was less potent than (-)-nicotine in eliciting hypothermia, seizures, death and reduction of locomotor activity in mice. The measured pharmacokinetic or brain disposition properties of ABT 418 in rats did not account for the observed enhancement in efficacy with reduced toxicity as compared to (-)-nicotine. The potent cognitive-enhancing and anxiolytic properties obtained for ABT 418 in animal models without eliciting significant side effects suggest that this ligand is a selective activator of cholinergic channel-mediated behaviors. Thus, ABT 418 may represent a novel, safe and effective treatment of the cognitive and emotional dysfunctions associated with Alzheimer's disease.

Alzheimer Disease↗

PubMed1994

(+/-)-Epibatidine elicits a diversity of in vitro and in vivo effects mediated by nicotinic acetylcholine receptors.

(+/-)-Epibatidine, exo-2-(6-chloro-3-pyridyl)-7-azabicyclo-[2.2.1] heptane, is a novel, potent analgesic agent that acts through nicotinic acetylcholine receptor (nAChR) mechanisms. This study sought to establish whether (+/-)-epibatidine, like (-)-nicotine, also displays a wide diversity of behavioral responses that are known to be elicited by nAChR activation or whether it demonstrates subtype selectivity for its interactions with nAChRs.(+/-)-Epibatidine displaced [3H](-)-cytisine binding to the alpha 4 beta 2 nAChR subtype in rat brain membranes with high affinity (Ki, 43 pM). The compound was approximately 5000-fold less potent (Ki = 230nM) in the displacement of [125I] alpha-bungarotoxin binding from the alpha-bungarotoxin-sensitive nAChR subtype present in rat brain but was a potent inhibitor (Ki, 2.7 nM) of [125I] alpha-bungarotoxin binding to the nAChR subtype in Torpedo electroplax, which is similar to that present in the neuromuscular junction. Functionally, (+/-)-epibatidine enhanced 86Rb+ flux in IMR 32 cells with an EC50 value of 7 nM. It was some 3000-fold more potent than (-)-nicotine (EC50 value, 21,000 nM) and was approximately 150-fold more potent (EC50 value, 0.4 nM) than (-)-nicotine (EC50 value = 60 nM) in increasing [3H]dopamine release from rat striatal slices. Remarkably, (+/-)-epibatidine was 40% to 50% more efficacious than (-)-nicotine in both functional assays. Both functional effects were blocked by the nAChR channel blocker, mecamylamine (100 microM). (+/-)-Epibatidine was 300 to 1000 times more potent than (-)-nicotine in the reduction of body temperature and locomotor activity in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

PubMed1993

Two crystal structures of a potently sweet protein. Natural monellin at 2.75 A resolution and single-chain monellin at 1.7 A resolution.

Two refined structures of the sweet-tasting protein monellin are presented. The structure of natural monellin has been refined at 2.75 A resolution. The final model consists of four monellin molecules in the asymmetric unit, encompassing 3136 non-hydrogen atoms. The crystallographic R-factor is 0.193 for the 8853 reflections between 6.0 A and 2.75 A resolution, and the root-mean-square deviations from ideality are 0.017 A for bond lengths and 3.6 degrees for bond angles. The refined structure generally confirms, with some difference in detail, the initial backbone model of monellin that was based on 3.0 A resolution data. Single-chain monellin (scm) was genetically engineered by fusing the two chains of monellin into a single 94-residue polypeptide. Using the refined monellin coordinates as a search model, the crystal structure of scm has been solved with the techniques of molecular replacement, and has been refined against data to 1.7 A resolution. The final model consists of two scm molecules per asymmetric unit, and includes 137 bound water molecules. The crystallographic R-factor for this model is 0.174 for the 15,053 reflections (magnitude of FO magnitude of > 2 sigma (FO)) between 6.0 A and 1.7 A resolution. The root-mean-square deviations from ideal bond lengths and angles are 0.015 A and 2.86 degrees, respectively, and the average coordinate error is approximately 0.2 A, as estimated from a Luzzati plot. The error in the model was also estimated by comparing the two molecules in the asymmetric unit. The most significant differences between the two molecules occur in loop regions and at the C terminus of the protein, and are generally correlated to differences in crystal packing contacts. Linking the two chains of monellin has not substantially altered the structure beyond the region immediately surrounding the new peptide bond. Like natural monellin, the conformation of scm is dominated by a 17-residue alpha-helix folded into the concave side of a twisted, five-strand anti-parallel beta-sheet. We expect that the availability of a high-resolution structure of scm, along with the convenience of producing site-specific mutants of this protein, will make scm a good model with which to probe the structural basis of sweetness.

Amino Acid Sequence↗

PubMed1993

Three-dimensional structures of the periplasmic lysine/arginine/ornithine-binding protein with and without a ligand.

Many proteins exhibit a large-scale movement of rigid globular domains. Among these, bacterial periplasmic binding proteins involved in substrate transport, or transport and chemotaxis, can be used as prototypes for understanding the mechanism of the movement. Such movements have been found to be associated with specific functions, such as substrate binding, catalysis, and recognition by other biomolecules. We have determined the three-dimensional structures of the lysine/arginine/ornithine-binding protein (LAO) from Salmonella typhimurium with and without lysine by x-ray crystallographic methods at 1.8- and 1.9-A resolution, respectively. The structures are composed of two lobes held together by two short connecting strands. The two lobes are far apart in the unliganded structure, but in contact with each other in the lysine-liganded structure. The large movement of the lobes is a consequence of a 52 degrees rotation of a single backbone torsion angle in the first connecting strand and of distributed smaller changes of three backbone torsion angles of the second connecting strand. The absence of contact between the lysine and the connecting strands suggests that the ligand does not induce the conformational change directly. We instead propose that the unliganded protein undergoes a dynamic change between an "open" and a "closed" conformation and that the role of the ligand is to stabilize the closed conformation. We discuss the nature of a surface area which might be recognized by the membrane-bound complex of these amino acids transport systems.

Amino Acid Sequence↗

PubMed1992

Crystallization and preliminary X-ray studies of the liganded lysine, arginine, ornithine-binding protein from Salmonella typhimurium.

The periplasmic binding protein LAO from Salmonella typhimurium, which is involved in lysine, arginine and ornithine transport, has been crystallized together with one of its ligands, arginine (LAO-Arg). Preliminary X-ray diffraction studies of LAO-Arg crystal show that it belongs to the orthorhombic space group P2(1)2(1)2(1) and has the unit cell dimensions of a = 37.65 A, b = 59.45 A, c = 115.91 A. Crystals of the LAO-Arg complex diffract beyond 2.0 A resolution.

Bacterial Proteins↗

PubMed1991

Crystal structure of the lysine-, arginine-, ornithine-binding protein (LAO) from Salmonella typhimurium at 2.7-A resolution.

A wide variety of sugars, amino acids, peptides, and inorganic ions are transported into bacteria by periplasmic transport systems consisting of substrate-specific receptors (binding proteins) and membrane-bound protein complexes. The crystal structure of the lysine-, arginine-, ornithine-binding protein (LAO) at 2.7-A resolution shows that the molecule has a bi-lobal structure and that its topological structure is different from other amino acid-binding proteins but is similar to the sulfate-binding protein and maltose-binding protein. High sequence homology between LAO and the histidine-binding protein (HisJ) and the fact that LAO and HisJ share the same membrane-bound protein complex allow one to define functional regions responsible for the ligand binding and for the interaction with the membrane complex.

Amino Acid Sequence↗

PubMed1991

Activation of the 5-HT1C receptor expressed in Xenopus oocytes by the benzazepines SCH 23390 and SKF 38393.

1. A cloned 5-HT1C receptor expressed in Xenopus laevis oocytes was used to characterize the action of four dopamine D1-selective benzazepines at the 5-HT1C receptor. Additionally, the apparent binding of the D1-selective benzazepines to 5-HT1C receptors was measured in the choroid plexus of the pig. 2. In voltage-clamped oocytes expressing the cloned 5-HT1C receptor, 5-hydroxytryptamine (5-HT) elicited a characteristic inward current response with an EC50 of 13 nM. SCH 23390 acted as a stereoselective agonist (or partial agonist) with an EC50 of about 550 nM. SKF 38393 (1 microM-1 mM), SKF 77434 (100 microM), and SKF 82958 (100 microM) also acted as agonists (or partial agonists) at the cloned 5-HT1C receptor. SKF 38393 was not stereoselective at the 5-HT1C receptor. 3. The response to SCH 23390 activated slowly and, although the response contained many oscillations characteristic of the activation of the phosphatidylinositol signal transduction system, SCH 23390 rarely elicited the rapid spike-like response seen routinely in response to 5-HT. However, the responses to SKF 38393, SKF 77434, and SKF 82958 were identical in appearance to the response to 5-HT, except that the responses to the benzazepines were smaller. These comparisons were made by applying both a benzazepine and 5-HT to each individual oocyte expressing the cloned 5-HT1C receptor. 4. Consistent with the responses measured in oocytes, SCH 23390 bound stereoselectively to 5-HT1C receptors in the choroid plexus of the pig (Ki = 6.3 nM), and SKF 38393 bound non-stereoselectively with lower affinity (Ki = 2.0-2.2 microM).5. It is concluded that while these benzazepines demonstrate selectivity for the dopamine D1 receptor, they also can act as agonists or partial agonists at the 5-HT1c receptor in situ and as expressed in Xenopus oocytes. The oocyte expression system is useful for studies of the functional pharmacology of these 5-HTic receptors. Information about the pharmacological actions and variations in stereoselectivity among dopamine and 5-HT receptors should be of interest in modelling the interactions of ligands with these G-protein coupled receptors, and in the testing of such models through receptor mutagenesis.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Crystallization and preliminary X-ray studies of HisJ and LAO periplasmic proteins from Salmonella typhimurium.

Two periplasmic binding proteins, HisJ and LAO, which are involved in histidine and arginine transport, respectively, have been crystallized. Preliminary X-ray diffraction studies of the HisJ and LAO crystals show that both belong to the orthorhombic space group P2(1)2(1)2(1) and have unit cell dimensions of a = 39.26 A, b = 66.17 A, c = 88.33 A and a = 36.08 A, b = 78.34 A, c = 102.02 A, respectively. Both HisJ and LAO crystals diffract beyond 2.0 A resolution.

Bacterial Proteins↗

PubMed1989

Redesigning a sweet protein: increased stability and renaturability.

Monellin is one of two natural proteins from African berries with potent sweet taste. Monellin is the smaller of the two, and consists of two peptides. The protein loses sweetness when heated above 50 degrees C under acidic pH. Based on the crystal structure of monellin we have fused the two chains into a single chain using several different linkers copied and 'transplanted' from the same molecule. One of the newly designed proteins is as potently sweet as the natural one, is more stable upon temperature or pH changes, and renatures easily even after heating to 100 degrees C at low pH.

Amino Acid Sequence↗