Biomedical subjects

J H Cho

Publications and source records attributed to J H Cho.

At least 55 records · Page 3Linked to original sources

PubMed2001

Treatment of severe equinus deformity associated with extensive scarring of the leg.

Nine severe equinus deformities of the foot associated with extensive scarring of the leg and ankle were corrected using a hinged Ilizarov apparatus and free-tissue transfer. The average duration of followup was 38 months (range, 28-54 months). Free tissue transfer was done in all patients; a parascapular flap was used in seven patients, and a groin flap was used in two patients. The results were evaluated using two objective criteria and one subjective assessment: the degree of active dorsiflexion, the range of active movement of the ankle, and daily activities. For active dorsiflexion of the ankle and activities, the results were good in seven patients and fair in two patients. For range of active motion of the ankle, the results were good in six patients and fair in two patients. One patient with ankle arthrodesis was excluded. This study showed that severe equinus deformities associated with extensive scarring of the leg and ankle can be corrected effectively with heel cord lengthening, free-tissue transfer, and a hinged Ilizarov technique.

Adolescent↗

PubMed2001

The Nod2 gene in Crohn's disease: implications for future research into the genetics and immunology of Crohn's disease.

The association of the Nod2 gene on chromosome 16 with increased susceptibility to Crohn's disease holds the promise of catalyzing fundamental genetic and therapeutic advances. Coding region variants in the leucine-rich repeat region of Nod2 may affect host interactions with bacterial lipopolysaccharide. Genetic differences in pattern-recognition proteins (such as Nod2) of the innate immune system represent an increasingly important paradigm for understanding host-environment interactions. The central problem for complex disease gene identification through genome-wide searches has been that of locus heterogeneity; it is hoped that this heterogeneity will recede with the identification of Nod2, as the first pieces of a puzzle accelerate placement of subsequent pieces. The potential for genetic approaches to positively impact the treatment of Crohn's disease and ulcerative colitis is unparalleled among complex, multigenic disorders.

Carrier Proteins↗

PubMed2001

Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice.

The epithelial cells of the gastrointestinal tract are exposed to toxins and infectious agents that can adversely affect protein folding in the endoplasmic reticulum (ER) and cause ER stress. The IRE1 genes are implicated in sensing and responding to ER stress signals. We found that epithelial cells of the gastrointestinal tract express IRE1beta, a specific isoform of IRE1. BiP protein, a marker of ER stress, was elevated in the colonic mucosa of IRE1beta(-/-) mice, and, when exposed to dextran sodium sulfate (DSS) to induce inflammatory bowel disease, mutant mice developed colitis 3-5 days earlier than did wild-type or IRE1beta(+/-) mice. The inflammation marker ICAM-1 was also expressed earlier in the colonic mucosa of DSS-treated IRE1beta(-/-) mice, indicating that the mutation had its impact early in the inflammatory process, before the onset of mucosal ulceration. These findings are consistent with a model whereby perturbations in ER function, which are normally mitigated by the activity of IRE1beta, participate in the development of colitis.

Animals↗

PubMed2001

Effects of cadmium on gap junctional intercellular communication in WB-F344 rat liver epithelial cells.

Cadmium has been associated with a number of tumors but its role in tumor promotion has not been elucidated clearly or the results obtained from various studies have been conflicting. This study was designed to investigate the effects of cadmium on the gap junctional intercellular communication (GJIC), number of gap junctions per cell, and cell proliferation in WB-F344 rat liver epithelial cells from the viewpoint of tumor promotion. GJIC was monitored by counting the cells stained with Lucifer yellow CH dye, using the scrape-loading and dye-transfer method. The numbers of gap junctions per cell were visually quantitated after an indirect immunostaining for gap junction protein using an antibody to connexin 43. Cell proliferation was assayed by direct counting of the living cells using the trypan blue dye exclusion method. In the time course study, cells treated with 200 microM CdCl2 showed rapid and nearly complete inhibition of GJIC (approximately 14% of the control) and a decrease in the number of gap junctions per cell (approximately 21% of the control) at 30 min, and the decrease continued up to 4 h without any changes in the cell viability. Treatment with CdCl2 (7.4-200 microM) for 4 h resulted in the decrease of GJIC and gap junction numbers per cell in a dose-response pattern without changes in the cell viability. In the long-term (14 days) exposure studies at doses of 0.01-7.4 microM CdCl2, an increase in cell proliferation was observed at low doses of 0.03-2.5 microM CdCl2, with GJIC also decreasing. These data demonstrate that cadmium inhibits GJIC, reduces the number of gap junctions per cell, and induces cell proliferation while decreasing the function of the gap junction.

Animals↗

PubMed2001

DNA methylation regulates placental lactogen I gene expression.

Expression of rat placental lactogen I is specific to the placenta and never expressed in other tissues. To obtain insight into the mechanism of tissue-specific gene expression, we investigated the methylation status in 3.4 kb of the 5'-flanking region of the rat placental lactogen I gene. We found that the distal promoter region of the rat placental lactogen I gene had more potent promoter activity than that of the proximal area alone, which contains several possible cis-elements. Although there are only 17 CpGs in the promoter region, in vitro methylation of the reporter constructs caused severe suppression of reporter activity, and CpG sites in the placenta were more hypomethylated than other tissues. Coexpression of methyl-CpG-binding protein with reporter constructs elicited further suppression of the reporter activity, whereas treatment with trichostatin A, an inhibitor of histone deacetylase, reversed the suppression caused by methylation. Furthermore, treatment of rat placental lactogen I nonexpressing BRL cells with 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, or trichostatin A resulted in the de novo expression of rat placental lactogen I. These results provide evidence that change in DNA methylation is the fundamental mechanism regulating the tissue-specific expression of the rat placental lactogen I gene.

Animals↗

PubMed2001

A novel membrane protein complex on the endoplasmic reticulum and early Golgi compartments in the yeast Saccharomyces cerevisiae.

A novel membrane protein, Yml067c in the systematic ORF name, was discovered as a component of immunoisolated vesicles of the early Golgi compartment of the yeast Saccharomyces cerevisiae (Cho et al., FEBS Lett. 469, 151-154 (2000)). Conserved sequences having sequence similarity to Yml067c were widely distributed in the eukaryotes and one of them, Yal042w, was found in the Saccharomyces genome database. In the yeast cell, Yml067c and Yal042w were found to form a heterooligomeric complex by immunoprecipitation of their tagged derivatives from the detergent-solubilized membrane. Cell fractionation and indirect immunofluorescent staining indicated that the majority of these proteins were localized on the ER membrane. Therefore, the Yml067c-Yal042w complex should shuttle between the ER and the early Golgi compartment as well as the p24-family proteins.

Amino Acid Sequence↗

PubMed2001

Activation of human monocyte cell line U937 via cell surface calreticulin.

U937 cells were found to be activated by an antibacterial peptide, KLKLLLLLKLK-NH2 (L5), to generate superoxide anion (O2-)-like peripheral neutrophils. However, the state of cell surface calreticulin, a possible receptor for L5, was suggested to differ between neutrophils and U937 cells. Unlike the former, the latter ones were activated by anti-C-domain peptide antibody of calreticulin even in the absence of L5 and generated O2- in a GTP-binding protein (G-protein)-dependent manner.

Animals↗

PubMed2001

A case of torsade de pointes associated with hypopituitarism due to hemorrhagic fever with renal syndrome.

We describe a 51-yr-old man presenting with syncope due to torsade de pointes. The torsade de pointes was refractory to conventional medical therapy, including infusion of isoproterenol, MgSO4, potassium, lidocaine, and amiodarone. His past history, physical findings, and hormone study confirmed that QT prolongation was caused by anterior hypopituitarism that developed as a sequela of hemorrhagic fever with renal syndrome. The long QT interval with deep inverted T wave was completely normalized 4 weeks after starting steroid and thyroid hormone replacement. Hormonal disorders should be considered as a cause of torsade de pointes, because this life-threatening arrhythmia can be treated by replacing the missing hormone.

Hemorrhagic Fever with Renal Syndrome↗

PubMed2001

Hyperfractionated re-irradiation using a 3-dimensional conformal technique for locally recurrent carcinoma of the nasopharynx; preliminary results.

To evaluate the efficacy of hyperfractionated re-irradiation using a three-dimensional conformal radiotherapy (3-D CRT) technique in patients with locally recurrent carcinoma of the nasopharynx. Four patients with locally recurrent nasopharyngeal cancer were retreated with a hyperfractionated schedule using a 3-D CRT technique. Re-irradiation was delivered in 1.1-1.2 Gy fractions twice per day (BID), with interfraction intervals of more than 6 hours. The total dose ranged from 59.4 to 69.2 Gy. A 3-D CRT technique with 5- or 6-field coplanar and/or non-coplanar beams were employed during the entire treatment procedure. All four patients achieved complete remission of locally recurrent lesions, with marked improvement of subjective symptoms, immediately after re-irradiation. All are alive and well without evidence of disease after limited follow-up periods, which range from 7 to 20 months. So far, there have been no radiation-induced neurologic complications. Four patients with locally recurrent carcinoma of the nasopharynx were successfully treated by hyperfractionated re-irradiation using a 3-D CRT technique. A relatively high re-irradiation dose of more than 60 Gy may be safely delivered with no serious acute or late radiation-induced complications in patients with local recurrences and who were initially treated with doses greater than 70 Gy.

Aged↗

PubMed2001

Closed-loop identification and control application for dissolved oxygen concentration in a full-scale coke wastewater treatment plant.

The objective of this paper is to apply a closed-loop identification to actual dissolved oxygen control system in the coke wastewater treatment plant. It approximates the dissolved oxygen dynamics to a high order model using the integral transform method and reduces it to the first-order plus time delay (FOPTD) or second-order plus time delay (SOPTD) for the PID controller tuning. To experiment the process identification on the real plant, a simple set-point change of the speed of surface aerator under the closed-loop control without any mode change was used as an activation signal of the identification. The full-scale experimental results show a good identification performance and a good tracking ability for set-point change. As a result of improved control performance, the fluctuation of dissolved oxygen concentration variation has been decreased and the electric power saving has been accomplished.

Biomass↗

PubMed2001

The antithrombotic efficacy of AT-1459, a novel, direct thrombin inhibitor, in rat models of venous and arterial thrombosis.

The antithrombotic efficacy of AT-1459, a novel, direct thrombin inhibitor (Ki = 4.9 nM) was evaluated in rat models of venous thrombosis combined with a bleeding time test and arterial thrombosis. After drugs were given by i. v. bolus injection plus a continuous infusion, the ID50, (a dose that exhibits 50% inhibition of thrombus formation over each vehicle group) values of AT-1459, argatroban, and dalteparin were 0.04 mg/kg plus 0.04 mg/kg/h, 0.1 mg/kg plus 0.4 mg/ kg/h, and 13.0 IU/kg plus 26.0 IU/kg/h, respectively, in the venous thrombosis study. The BT2 (a dose that causes 2-fold prolongation of bleeding time over each vehicle group) values of AT-1459, argatroban, and dalteparin were 0.9 mg/kg plus 0.9 mg/kg/h, 1.0 mg/kg plus 0.6 mg/kg/h, and 345.5 IU/kg plus 691.0 IU/kg/h in the rat tail transection model. The ratios of BT2/ID50 of AT-1459, argatroban, and dalteparin were 22.5, 10.0, and 26.6, respectively. In a rat model of arterial thrombosis induced by topical FeCl2 application, intravenous administration of AT-1459, argatroban, and dalteparin improved the vessel patency significantly (P < 0.01) at 0.6 mg/kg plus 0.6 mg/kg/h, 0.6 mg/kg plus 2.4 mg/kg/h, and 300 IU/kg plus 600 IU/kg/h, respectively. The oral antithrombotic effect of AT-1459 lasted for 6 after administering 30 mg/kg and improved the vessel patency significantly 1 h after administering the same dose in venous and arterial thrombosis models, respectively, with a rapid onset of action. Warfarin also inhibited thrombus weight and improved the vessel patency significantly after oral administration of 0.3 mg/kg for three consecutive days in the same study. The antithrombotic and hemorrhagic effects of all drugs studied were correlated with plasma concentration or clotting times. These results suggest that AT-1459 may be clinically useful as an orally available antithrombotic agent for the prevention of venous and arterial thrombosis.

Administration, Oral↗

PubMed2000

Two isoforms of sarco/endoplasmic reticulum calcium ATPase (SERCA) are essential in Caenorhabditis elegans.

SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase), a membrane bound Ca(2+)- /Mg(2+)- dependent ATPase that sequesters Ca(2+) into the SR/ER lumen, is one of the essential components for the maintenance of intracellular Ca(2+) homeostasis. Here we describe the identification and functional characterization of a C. elegans SERCA gene (ser-1). ser-1 is a single gene alternatively spliced at its carboxyl terminus to form two isoforms (SER-1A and SER-1B) and displays a high homology (70% identity, 80% similarity) with mammalian SERCAs. Green fluorescent protein (GFP) and whole-mount immunostaining analyses reveal that SER-1 expresses in neuronal cells, body-wall muscles, pharyngeal and vulval muscles, excretory cells, and vulva epithelial cells. Furthermore, SER-1::GFP expresses during embryonic stages and the expression is maintained through the adult stages. Double-stranded RNA injection (also known as RNAi) targeted to each SER-1 isoform results in severe phenotypic defects: ser-1A(RNAi) animals show embryonic lethality, whereas ser-1B(RNAi) results in L1 larval arrest phenotype. These findings suggest that both isoforms of C. elegans SERCA, like in mammals, are essential for embryonic development and post-embryonic growth and survival.

Alternative Splicing↗

PubMed2000

Equilibrium and kinetic analysis of folding of ketosteroid isomerase from Comamonas testosteroni.

Equilibrium and kinetic analyses have been carried out to elucidate the folding mechanism of homodimeric ketosteroid isomerase (KSI) from Comamonas testosteroni. The folding of KSI was reversible since the activity as well as the fluorescence and CD spectra was almost completely recovered after refolding. The equilibrium unfolding transitions monitored by fluorescence and CD measurements were almost coincident with each other, and the transition midpoint increased with increasing protein concentration. This suggests that the KSI folding follows a simple two-state mechanism consisting of native dimer and unfolded monomer without any thermodynamically stable intermediates. Sedimentation equilibrium analysis and size-exclusion chromatography of KSI at different urea concentrations supported the two-state model without any evidence of folded monomeric intermediates. Consistent with the two-state model, (1)H-(15)N HSQC spectra obtained for KSI in the unfolding transition region could be reproduced by a simple addition of the spectra of the native and the unfolded KSI. The KSI refolding kinetics as monitored by fluorescence intensity could be described as a fast first-order process followed by a second-order and a subsequent slow first-order processes with rate constants of 60 s(-)(1), 5.4 x 10(4) M(-)(1).s(-)(1), and 0.017 s(-)(1), respectively, at 0.62 M urea, suggesting that there may be a monomeric folding intermediate. After a burst phase that accounts for >83% of the total amplitude, the negative molar ellipticity at 225 nm increased slowly in a single phase at a rate comparable to that of the bimolecular intermediate step. The kinetics of activity recovery from the denatured state were markedly dependent upon the protein concentration, implying that the monomers are not fully active. Taken together, our results demonstrate that the dimerization induces KSI to fold into the complete structure and is crucial for maintaining the tertiary structure to perform efficient catalysis.

Chromatography, Gel↗

PubMed2000

Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease.

The idiopathic inflammatory bowel diseases (IBDs), consisting of Crohn's disease and ulcerative colitis, are complex genetic disorders involving chronic inflammation of the intestines. Multiple genetic loci have been implicated through genome-wide searches, but refinement of localization sufficient to undertake positional cloning efforts has been problematic. This difficulty can be obviated through identification of ancestrally shared regions in genetic isolates, such as the Chaldean population, a Roman Catholic group from Iraq. We analyzed four multiply affected American Chaldean families with inflammatory bowel disease not known to be related. We observed evidence for linkage and linkage disequilibrium in precisely the same region of chromosome band 1p36 reported previously in an outbred population. Maximal evidence for linkage was observed near D1S1597 by multipoint analysis (MLOD = 3.01, P = 6.1 x 10(-5)). A shared haplotype (D1S507 to D1S1628) was observed over 27 cM between two families. There was homozygous sharing of a 5 cM portion of that haplotype in one family and over a <1 cM region in the second family. Homozygous sharing of this haplotype near D1S2697 and D1S3669 was observed in one individual in a third multiply affected family, with heterozygous sharing in a fourth family. Linkage in outbred families as well as in this genetic isolate indicates that a pathophysiologically crucial IBD susceptibility gene is located in 1p36. These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder.

Chromosomes, Human, Pair 1↗

PubMed2000

Nuclear magnetic resonance solution conformation of alpha-conotoxin AuIB, an alpha(3)beta(4) subtype-selective neuronal nicotinic acetylcholine receptor antagonist.

The neuronal nicotinic acetylcholine receptors constitute a highly diverse group, with subtypes consisting of pentameric combinations of alpha and beta subunits. alpha-Conotoxins are a homologous series of small peptides that antagonize these receptors. We present the three-dimensional solution structure of alpha-conotoxin AuIB, the first 15-residue alpha-conotoxin known to selectively block the alpha(3)beta(4) nicotinic acetylcholine receptor subtype. The pairwise backbone and heavy-atom root mean square deviation for an ensemble of 20 structures are 0.269 and 0.720 A, respectively. The overall fold of alpha-conotoxin AuIB closely resembles that of the alpha4/7 subfamily alpha-conotoxins. However, the absence of Tyr(15), normally present in other alpha4/7 members, results in tight bending of the backbone at the C terminus and effectively renders Asp(14) to assume the spatial location of Tyr(15) present in other neuronal alpha4/7 alpha-conotoxins. Structural comparison of alpha-conotoxin AuIB with the alpha(3)beta(2) subtype-specific alpha-conotoxin MII shows different electrostatic surface charge distributions, which may be important in differential receptor subtype recognition.

Amino Acid Sequence↗

PubMed2000

Proteins in the early golgi compartment of Saccharomyces cerevisiae immunoisolated by Sed5p.

The yeast tSNARE Sed5p is considered to mainly reside in the early Golgi compartment at the steady state of its intracellular cycling. To better understand this compartment, we immunoisolated a membrane subfraction having Sed5p on the surface (the Sed5 vesicles). Immunoblot studies showed that considerable portions (20-30%) of the Golgi mannosyltransferases (Mnt1p, Van1p, and Mnn9p) were simultaneously recovered while the late Golgi (Kex2p) or endoplasmic reticulum (Sec71p) proteins were almost excluded. The N-terminal sequences of the polypeptides detectable by Coomassie blue staining indicated that the prominent components of the Sed5 vesicles include Anp1p, Emp24p, Erv25p, Erp1p, Ypt52p, and a putative membrane protein of unknown function (Yml067c).

Carrier Proteins↗

PubMed2000

Expression of neuroD/BETA2 in mitotic and postmitotic neuronal cells during the development of nervous system.

NeuroD/BETA2, a basic helix-loop-helix transcription factor, has been shown to play a role in tissue-specific differentiation of pancreatic and enteroendocrine cells. To gain further insight into the function of neuroD/BETA2 in the nervous system development, we examined the expression pattern of neuroD/BETA2 during embryonic and postnatal development by using in situ hybridization. Dynamic changes of neuroD/BETA2 expression in the central nervous system were observed during embryogenesis, especially in telencephalon, hippocampus, cerebellum, spinal cord, and olfactory epithelium. Moderate level of expression was also detected in developing pancreas in early embryogenesis. Although the neuroD/BETA2 expression in cerebellum and hippocampus increased over time, expression in cerebral cortex, spinal cord, as well as in fetal pancreas gradually decreased as embryogenesis proceeded. High level of the neuroD/BETA2 expression in developing cerebellum and hippocampus persisted throughout postnatal development and remained at a stable level in the adult brain. Interestingly, neuroD/BETA2 expression was detected not only in postmitotic but also in mitotic cells, as was evident in its expression in external granular layer of cerebellum and granule cells of the dentate gyrus during postnatal development. This observation suggests that neuroD/BETA2 may have a unique role in proliferation, differentiation, or both, of granule cells of cerebellum and dentate gyrus.

Animals↗

PubMed2000

Development of rapid one-step immunochromatographic assay.

An analytical system for a one-step immunoassay has been constructed using the concept of immunochromatography. The system employed two different antibodies that bound distinct epitopes of an analyte molecule: an antibody labeled with a signal generator (e.g., colloidal gold), which was placed in the dry state at a predetermined site on a glass-fiber membrane, and another antibody immobilized on the surface of a nitrocellulose membrane. Three membranes, one with the tracer, one with immobilized antibody, and a cellulose membrane as the absorbent of medium (in a sequence from the bottom), were attached to a plastic film and cut into strips. Aqueous medium containing analyte absorbed from the bottom end of the immunostrip dissolved the labeled antibody, and the antigen-antibody binding complex formed was transported into the next nitrocellulose membrane by the flow caused by capillary action. The complex subsequently reacted with the immobilized antibody, which generated a signal in proportion to the analyte concentration. The convective mass transfer of the immunoreactant to the binding partner allowed the assay to be performed with no handling of reagents. The reaction, however, was carried out under nonequilibrium conditions, which resulted in decreased sensitivity as compared with assays performed in an equilibrium mode (e.g., ELISA). To minimize such sacrifice, major factors that control system performance were identified and the system was then devised under optimal conditions.

Animals↗