Crystal structures of orotidine monophosphate decarboxylase: does the structure reveal the mechanism of nature's most proficient enzyme?
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Crystallography, X-Ray↗
Biomedical subjects
J K Lee
Publications and source records attributed to J K Lee.
Protective effect of green tea extract on ischemia/reperfusion-induced brain injury in Mongolian gerbils.
Free radical-induced oxidative damages of macromolecules and cell death are important factors in the pathogenesis of ischemia/reperfusion brain injury. In the present study, an investigation as to whether green tea extract reduces ischemia/reperfusion-induced brain injury in Mongolian gerbils was conducted. The effect of green tea on the ischemia/reperfusion-induced production of hydrogen peroxide, lipid peroxidation and oxidative DNA damage (formation of 8-hydroxydeoxyguanosine), and cell death in addition to locomotor activity was studied. Two doses (0.5 or 2%) of green tea extract were added into the drinking water and to be accessed by animals ad libitum for 3 weeks prior to the induction of ischemia. A global ischemia was induced by the bilateral occlusion of the common carotid arteries for 5 min. Reperfusion was achieved by releasing the occlusion and restoring blood circulation for 48 h. The infarction volumes were 112+/-31 mm(3) and 76+/-11 mm(3) in the 0.5 and 2% green tea pretreated animals compared to 189+/-12 mm(3) in the ischemia/reperfusion animals. Green tea extract also reduced the levels of ischemia/reperfusion-induced hydrogen peroxide (from 1470+/-170 to 1034+/-46 and 555+/-30 nmole/mg protein), lipid peroxidation products (from 1410+/-210 to 930+/-40 and 330+/-20 nmole/mg protein) and 8-oxodG (from 3.9+/-0.1 to 2.8+/-0.3 and1.9+/-0.3 ng/microg DNA, x10(-2)) by pretreatment of 0.5 or 2% green tea for 3 weeks, respectively. Moreover, green tea also reduced the number of ischemia/reperfusion-induced apoptotic cells (from 59+/-12 to 37+/-8, 15+/-11 apoptotic cells/high power field in the striatum region) and locomotor activity (from 15140+/-2940 to 3900+/-600 and 4100+/-1200). This study therefore suggests that green tea may be a useful agent for the prevention of cerebral ischemia damage.
8-Hydroxy-2'-Deoxyguanosine↗
Processive DNA helicase activity of the minichromosome maintenance proteins 4, 6, and 7 complex requires forked DNA structures.
The minichromosome maintenance (Mcm) proteins 2-7 are required for both the initiation and elongation steps of chromosomal DNA replication. Previous studies have shown that the Mcm complex consisting of the Mcm 4, 6, and 7 proteins contains 3' to 5' DNA helicase activity with limited processivity (displacing duplex DNA regions up to 30 nt). In this report, we show that the presence of both 5' and 3' single-stranded tails in DNA helicase substrates is essential for the processive helicase activity of the Mcm complex. The presence of both 5' and 3' tails facilitated the formation of double heterohexameric complexes of Mcm4/6/7 on substrate DNA, which appeared to be essential for the processive helicase activity. The double heterohexameric complex of Mcm4/6/7, in the presence of a single-strand DNA binding protein, is capable of unwinding duplex DNA region of about 600 bp in length. These results support the hypothesis that the Mcm4/6/7 complex can function as a replication helicase.
Cell Cycle Proteins↗
The incidence of hip fracture in four Asian countries: the Asian Osteoporosis Study (AOS).
The Asian Osteoporosis Study (AOS) is the first multicenter study to document and compare the incidence of hip fracture in four Asian countries. Hosital discharge data for the year 1997 were obtained for the Hong Kong SAR, Singapore, Malaysia and Thailand (Chiang Mai). The number of patients who were 50 years of age and older and who were discharged with a diagnosis of hip fracture (ICD9 820) was enumerated. The age-specific incidence rates were deduced and were directly adjusted to the US white population in 1989. The age-adjusted rates for men and women (per 100,000) are as follows: Hong Kong, 180 and 459; Singapore, 164 and 442; Malaysia, 88 and 218; Thailand, 114 and 289; compared with US White rates of 187 in men and 535 in women, published in 1989. We conclude that there is moderate variation in the incidence of hip fracture among Asian countries. The rates were highest in urbanized countries. With rapid economic development in Asia, hip fracture will prove to be a major public health challenge.
Aged↗
Activity of descending contralateral movement detector neurons and collision avoidance behaviour in response to head-on visual stimuli in locusts.
We recorded the activity of the right and left descending contralateral movement detectors responding to 10-cm (small) or 20-cm (large) computer-generated spheres approaching along different trajectories in the locust's frontal field of view. In separate experiments we examined the steering responses of tethered flying locusts to identical stimuli. The descending contralateral movement detectors were more sensitive to variations in target trajectory in the horizontal plane than in the vertical plane. Descending contralateral movement detector activity was related to target trajectory and to target size and was most sensitive to small objects converging on a direct collision course from above and to one side. Small objects failed to induce collision avoidance manoeuvres whereas large objects produced reliable collision avoidance responses. Large targets approaching along a converging trajectory produced steering responses that were either away from or toward the side of approach of the object, whereas targets approaching along trajectories that were offset from the locust's mid-longitudinal body axis primarily evoked responses away from the target. We detected no differences in the discharge properties of the descending contralateral movement detector pair that could account for the different collision avoidance behaviours evoked by varying the target size and trajectories. We suggest that descending contralateral movement detector properties are better suited to predator evasion than collision avoidance.
Animals↗
Cervical dermal sinus associated with dermoid cyst.
We report a rare case of cervical dermal sinus associated with a dermoid cyst in a 10-month-old infant, who presented with a 1-month history of motor weakness of the right upper extremity. Magnetic resonance imaging showed an intradural extramedullary dermoid cyst extending from C3 to C4, which was connected with the skin dimple along the sinus tract. Total excision of the dermoid cyst and the sinus tract with C3-5 laminectomy resulted in good functional recovery.
Cervical Vertebrae↗
Inhibitory action of water soluble fraction of Terminalia chebula on systemic and local anaphylaxis.
We investigated the effects of the water soluble fraction of Terminalia chebula (Combretaceae) (WFTC) on systemic and local anaphylaxis. WFTC administered 1h before compound 48/80 injection inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.01-1.0 g/kg. When WFTC was administered 5 or 10 min after compound 48/80 injection, the mortality also decreased in a dose-dependent manner. Passive cutaneous anaphylaxis was inhibited by 63.5+/-7.8% by oral administration of WFTC (1.0 g/kg). When WFTC was pretreated at concentrations ranging from 0.005 to 1.0 g/kg, the serum histamine levels were reduced in a dose-dependent manner. WFTC (0.01-1.0 mg/ml) also significantly inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. However, WFTC (1.0 mg/ml) had a significant increasing effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that WFTC may possess a strong antianaphylactic action.
Anaphylaxis↗
Development and application of a sorption data base for the performance assessment of a radwaste repository.
A sorption data base (SDB) provides readily available data for the performance assessment of a radwaste repository when site-specific and/or reference data are needed. The software developed at KAERI, SDB-21C, is a graphic user interface (GUI) program that provides efficient and user-friendly tools for evaluating large amount of sorption data. In addition, the most comprehensive sorption data base that contains about 11,000 NEA data and 2,000 KAERI data was compiled in the program. Besides the simple Kd approach, a parametric model and its compiled data sets are also included in the SDB-21C. In order to evaluate the versatility of SDB-21C, several applications were performed for relevant hypothetical situations.
Adsorption↗
A non-calcemic analog of 1 alpha,25 dihydroxy vitamin D(3) (JKF) upregulates the induction of creatine kinase B by 17 beta estradiol in osteoblast-like ROS 17/2.8 cells and in rat diaphysis.
We have reported that multiple treatments with so-called 'non-hypercalcemic' analogs of 1 alpha,25(OH)(2) vitamin D(3) (1,25(OH)(2)D(3)) stimulate the specific activity of creatine kinase BB (CK) in ROS 17/2.8 osteoblast-like cells, and that pretreatment with these analogs upregulates responsiveness and sensitivity to 17 beta estradiol (E(2)) for the induction of CK. However, since the analogs showed toxicity in vivo, we have now studied the action of a demonstrably non-calcemic hybrid analog of vitamin D in ROS 17/2.8 cells, and prepubertal rats. The analog JKF was designed to separate its calcemic activity from other biological activities by combining a calcemic-lowering 1-hydroxymethyl group with a potentiating C, D-ring side chain modification including 24 difluoronation. Treatment with 1 pM JKF alone significantly stimulated CK specific activity at 4 h by 30+/-10%. However after three daily pretreatments, JKF upregulated the extent of induction by 30 nM E(2) by 33% at 1 pM and by 97% at 1 nM; the E(2) dose needed for a significant stimulation of CK activity was lowered to 30 pM. The action of the SERMS tamoxifen, tamoxifen methiodide and raloxifene, at 3 microM, was also upregulated by three daily pretreatments with 1 nM JKF; unexpectedly, this pretreatment prevented the inhibition of E(2) stimulation by the SERMS. Upregulation of E(2) action by 1 nM JKF was inhibited by 1 nM ZK159222, an inhibitor of the nuclear action of 1,25(OH)(2)D(3). In vivo, three daily injections of 0.05 ng/g body weight of JKF augmented the response of prepubertal female rat diaphysis and epiphysis to E(2). Therefore, demonstrably non-calcemic analogs of 1,25(OH)(2)D(3) may have potential for use in combination with estrogens or SERMS in the prevention and/or treatment of metabolic bone diseases such as postmenopausal osteoporosis.
Animals↗
Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes.
Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombinant L-selectin to the luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost from the luminal aspects of HEV. These results establish a critical role for HEC-GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic target.
Animals↗
Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells.
Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have antiviral and antitumoral activities in vivo through activation of immune responses. The present study was set out to define the immunomodulatory activity of acemannan on dendritic cells (DCs), which are the most important accessory cells for the initiation of primary immune responses. Immature DCs were generated from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM-CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS, respectively. The resultant DCs were examined for phenotypic and functional properties. Phenotypic analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that acemannan could induce maturation of immature DCs. Functional maturation of immature DCs was supported by increased allogeneic mixed lymphocyte reaction (MLR) and IL-12 production. The differentiation-inducing activity of acemannan was almost completely abolished by chemical sulfation. Based on these results, we propose that the adjuvant activity of acemannan is at least in part due to its capacity to promote differentiation of immature DCs.
Adjuvants, Immunologic↗
Development of an ELISA for the detection of the residues of the insecticide imidacloprid in agricultural and environmental samples.
A competitive enzyme-linked immunosorbent assay (ELISA) for the chloronicotinyl insecticide imidacloprid was developed using a polyclonal antibody produced against a hapten conjugated through the imidazolidine to keyhole limpet hemocyanin. In the standard curve of imidacloprid, an IC(50) of 17.3 ng/mL was obtained using a competitive heterologous system at pH 10. Very low cross-reactivity was found for some structurally related compounds including the insecticide thiacloprid. The high cross-reactivity with a metabolite containing the carbonyl group in the imidazolidine moiety suggests the involvement of its polarity and stereochemical fitness in forming the antibody--antigen complex. The effects of various assay conditions, including organic solvents, detergent content, salt concentration, and pH on the sensitivity were evaluated. High-performance liquid chromatography was run for comparison to validate the ELISA with fortified water samples, the correlation being 0.997-0.998 (n = 15) with a slope of 1.10--1.38. The ELISA turned out to be a convenient tool for monitoring imidacloprid residues in agricultural and environmental samples.
Chromatography, High Pressure Liquid↗
High signal intensity of the posterior pituitary gland on T1-weighted MR images. Correlation with plasma vasopressin concentration to water deprivation.
PURPOSE: To evaluate the effect of water deprivation on the signal intensity of the posterior pituitary gland on T1-weighted MR images and correlate the signal intensity with the plasma vasopressin concentration. MATERIAL AND METHODS: Fifteen rabbits were studied: Group 1 (n=10) was deprived of water for 9 days and Group 2 (n=5) was replenished water for 7 days after 7-day water deprivation. MR imaging and plasma vasopressin measurement by radioimmunoassay were made before and after water deprivation and replenishment. Sequential changes of the signal intensity ratio of the posterior lobe to the pons and plasma vasopressin concentration were correlated. RESULTS: Before water deprivation, the hyperintense posterior lobe was demonstrated in all rabbits. During water deprivation, the signal intensity ratio decreased and vasopressin concentration increased gradually. On the contrary, the signal intensity ratio increased and vasopressin concentration decreased with water replenishment. The signal intensity ratio correlated well with the plasma vasopressin concentration (p<0.05). CONCLUSION: There was a negative, linear correlation between the signal intensity ratio of the posterior pituitary gland on T1-weighted MR images and plasma vasopressin concentration to water deprivation. The results support that the high signal intensity of the posterior pituitary gland on T1-weighted MR images is attributed to the normal content of vasopressin-neurosecretory granules.
Animals↗
Increased erythritol production in fed-batch cultures of Torula sp. by controlling glucose concentration.
The effect of glucose concentration on erythritol production by Torula sp. was investigated. The maximum volumetric productivity of erythritol was obtained at an initial glucose concentration of 300 g l(-1) in batch culture. The volumetric productivity was maximal at a controlled glucose concentration of 225 g l(-1), reducing the lag time of the erythritol production. A fed-batch culture was established with an initial glucose concentration of 300 g l(-1) and with a controlled glucose concentration of 225 g l(-1) in medium containing phytic acid as a phosphate source. In this fed-batch culture, a final erythritol production of 192 g l(-1) was obtained from 400 g l(-1) glucose in 88 h. This corresponded to a volumetric productivity of 2.26 g l(-1) h(-1) and a 48% yield.
Cell Division↗
Unilateral gallium-67 citrate uptake in mucosa-associated lymphoid tissue lymphoma of the parotid gland.
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Aged↗
The clinical significance of common bile-duct dilatation in patients without biliary symptoms or causative lesions on ultrasonography.
BACKGROUND AND STUDY AIMS: Although abdominal ultrasonography (US) is a good initial screening method for detection of biliary tract disease, we sometimes encounter patients who only have findings of dilatation of the common bile duct (CBD) on US, without specific biliary symptoms or jaundice. This study aimed to evaluate the causes and clinical significance of dilatation of the CBD in patients without biliary symptoms, jaundice, or causative lesions at US. PATIENTS AND METHODS: A total of 77 patients who had no biliary symptoms and whose internal CBD diameter was more than 7 mm, without definite causative lesions on US, were enrolled. Of these, 49 underwent endoscopic retrograde cholangiopancreatography (ERCP) and 28 underwent follow-up US or computed tomography (CT) instead of ERCP. We excluded patients whose bilirubin level had increased beyond the upper normal level or who had previous history of upper abdominal surgery including cholecystectomy. RESULTS: The ERCP findings were as follows: no lesion in 20 patients (40.8%), juxtapapillary duodenal diverticulum (JDD) in 11 (22.5%), benign stricture in ten (20.4%), distal CBD mass in two (4.1%), choledochal cyst in two (4.1%), anomalous union of the pancreaticobiliary duct (AUPBD) in two (4.1%), and choledochal cyst with AUPBD in two (4.1%). There were no differences in age or in alkaline phosphatase or gamma-glutamyl transpeptidase (GGT) levels between the patients who had causative lesions revealed at ERCP and those who did not. Among the 28 patients who did not undergo ERCP, 12 had returned to normal and eight had no change in CBD diameter on follow-up US. Among eight patients who underwent CT, there were four with normal findings, one with JDD, and three with suspected choledochal cysts. CONCLUSIONS: We detected a significant number of causative biliary tract lesions in asymptomatic adults with dilatation of the CBD on routine abdominal US; no laboratory or demographic parameters were useful for discrimination. Further diagnostic study will be helpful for the early diagnosis of biliary tract disease in such patients.
Adult↗
Safety and feasibility of a novel rate-smoothed ventricular pacing algorithm for atrial fibrillation.
OBJECTIVES: This study was conducted to establish the safety and performance of a new rate-smoothing pacing algorithm for patients with atrial fibrillation (AF). BACKGROUND: Irregularity of the ventricular response is a hallmark of AF. This irregularity may contribute to symptoms and hemodynamic compromise in patients with AF. Interventions designed to reduce irregularity have not previously been evaluated in a long-term, clinical setting. METHODS: We designed a prospective, double-blind study with randomized crossover. Patients with either paroxysmal or chronic AF whose conditions were medically refractory and who were referred for an atrioventricular node ablation procedure all underwent pacemaker implantation. Subjects were then randomly assigned to either DDD mode with the rate-smoothing algorithm (RSA) on, or to OOO mode. After 2 months they were crossed over to the other arm. RESULTS: Fourteen patients (9 with paroxysmal AF and 5 with chronic AF) were enrolled. There were no significant differences between the group randomly assigned to RSA first versus the group assigned to OOO first. The mean left ventricular ejection fraction with the RSA was not significantly different than it was in OOO mode (45.1 +/- 18.6 vs 51.9 +/- 12.3; P =.11), although some individuals with uncontrolled ventricular rates did have a large decrease in ejection fraction with rate smoothing. One developed overt heart failure. One quality-of-life instrument detected a significant improvement in the "physical limitations" domain with the rate-smoothing mode. Eleven of 14 patients preferred the RSA ON arm, and 6 of those 11 elected to defer the ablation procedure. CONCLUSIONS: Long-term rate-smoothed pacing is feasible. Because of concerns about pacing-induced heart failure in some patients with rapid ventricular rates, rate-smoothed pacing should be reserved for those who remain symptomatic despite adequate control of the ventricular rate. The RSA may help to reduce symptoms in patients with medically refractory AF; more study is required to define its efficacy in reducing symptoms and morbidity in this population.
Aged↗
Simultaneous analysis of 1176 gene products in normal human aorta and abdominal aortic aneurysms using a membrane-based complementary DNA expression array.
BACKGROUND: A number of changes in gene expression have been described in abdominal aortic aneurysms (AAAs), but the spectrum of molecular alterations in this disease is unknown. The purpose of this study was to characterize the expression of approximately 1000 gene products in human AAA tissue and to compare the profile of genes expressed in AAAs with that observed in normal aorta. MATERIALS AND METHODS: Total RNA was isolated from abdominal aortic wall tissues (4 AAAs and 4 normal aortas), and array-specific [(32)P]-labeled complementary DNA (cDNA) probes were created with reverse transcription. The cDNA probes were hybridized with nylon membranes containing an array of 1176 cDNA clones (AtlasArray Human 1.2 I; Clontech, Palo Alto, Calif), and autoradiographs were scanned to identify the patterns of gene expression characteristic of each tissue type. Densitometric analysis was used to standardize the expression of individual genes to a panel of housekeeping controls, and differential gene expression was defined by a signal ratio of at least 2:1. RESULTS: One hundred forty-five (12.3%) of the 1176 genes were consistently expressed in aortic tissue. Thymosin beta-4 was the most abundant of 101 transcripts detected in both AAAs and normal aorta, whereas 44 genes exhibited differential patterns of expression (39 predominant in AAAs and 5 in normal aorta). Densitometric analysis confirmed differences in expression for 20 of these gene products between AAAs and normal aorta, with the greatest increases seen for myeloid cell nuclear differentiation antigen (31-fold), cathepsin H (30-fold), platelet-derived growth factor-A (23-fold), apolipoprotein E (13-fold), gelatinase B/matrix metalloproteinase-9 (12-fold), and interleukin-8 (11-fold). The only gene products substantially decreased in AAAs were myosin light chain kinase (39-fold) and beta-1 integrin (twofold). AAA tissues thereby exhibited a distinct pattern of gene expression reflecting chronic inflammation, extracellular matrix degradation, atherosclerosis, and smooth muscle cell depletion. CONCLUSIONS: cDNA expression arrays provide a powerful new approach to help identify the molecular mechanisms responsible for aneurysmal degeneration. Further studies will be needed to elucidate the functional and pathophysiologic significance of the individual genes that exhibit altered levels of expression in AAA tissue.
Aged↗