Biomedical subjects

H S Shin

Publications and source records attributed to H S Shin.

At least 109 records · Page 6Linked to original sources

PubMed1997

Helicobacter pylori infection and the risk of gastric cancer among the Korean population.

Helicobacter pylori infection has been associated with chronic atrophic gastritis, a precursor of gastric cancer. We conducted a prospective, case-controlled study to investigate whether H. pylori infection increases the risk of gastric cancer in Korean people with a high risk of gastric cancer. We enrolled 160 gastric cancer patients who were confirmed by endoscopic biopsy during 1994 and 160 age-matched control subjects with non-ulcer dyspepsia were compared to document the relationship between H. pylori infection and gastric cancer. The presence of H. pylori infection was determined by the rapid urease test and/or histology by Wright-Giemsa staining. The overall presence of H. pylori infection was 60% in gastric cancer patients and 51.9% in age-matched control subjects (odds ratio 1.39; 95% confidence interval 0.894-2.17; P = 0.143). Carcinomas of cardia, body and antrum were not associated with H. pylori infection (odds ratio 1.43, 1.69 and 1.29, respectively; 95% confidence interval, 0.271-7.52, 0.787-3.62 and 0.689-2.43, respectively; P = 0.178, 0.177 and 0.642, respectively) nor was the intestinal or diffuse type of cancer (odds ratio 1.39 and 1.40, respectively; 95% confidence interval 0.791-2.45 and 0.681-2.87, respectively; P = 0.250 and 0.835, respectively). Gender was not a risk for gastric cancer. In contrast to previous studies, these results do not provide evidence of H. pylori infection for gastric carcinogenesis in Korea.

Adenocarcinoma↗

PubMed1997

Interaction of nitric oxide and the renin angiotensin system in renal hypertensive rats.

We investigated the interaction between nitric oxide and the renin angiotensin system in regulating isolated aortic tension and mean arterial pressure in renal hypertensive rats (RHR). Acetylcholine (ACh) relaxed aorta precontracted with norepinephrine from RHR significantly less than that from normotensive rats (NR) (Emax: 34.3% and 86.0%, respectively, P < 0.01). The ACh-induced relaxation was significantly enhanced by losartan (P < 0.05) and completely abolished by removal of endothelium or NG-nitro-L-arginine methyl ester (L-NAME). ACh lowered the mean arterial pressure slightly less effectively in RHR than in NR (6.8 and 13.0 mmHg, respectively, at 0.1 microgram/kg), whereas the depressor effect was reduced by L-NAME (-15.5 and 10.3 mmHg, respectively, at 0.1 microgram/kg), but rather enhanced by further treatment with losartan (9.9 (P < 0.05) and 17.3 mmHg, respectively, at 0.1 microgram/kg). Angiotensin II induced similar contractile and pressor responses in both RHR and NR, and these effects were significantly enhanced by L-NAME, except for the pressor effect in RHR. L-NAME induced a similar pressor response in RHR and NR (15.9 and 15.2 mmHg, respectively, at 0.1 mg/kg), the effect being decreased by pretreatment with losartan. Losartan induced a depressor response that was smaller in RHR than in NR (34.0 and 48.8 mmHg, respectively, at 0.3 mg/kg), and the response was significantly reduced by L-NAME. These results suggest that nitric oxide interacts with the renin angiotensin system to control the vascular tension and systemic arterial circulation in RHR.

Angiotensin II↗

PubMed1997

Metabolism of selegiline in humans. Identification, excretion, and stereochemistry of urine metabolites.

Nine urinary metabolites of selegiline hydrochloride [N-methyl-N-propargyl [2-phenyl-1-methyl)ethylammonium chloride], a monoamine oxidase inhibitor, after administration to humans were identified. Their identifies were confirmed by comparison of the spectra from GC/MS of peaks with those of authentic compounds. The following metabolites and unchanged drug (selegiline) were detected in urine: (R)-desmethylselegiline, (R)-methamphetamine, (R)-amphetamine, (1S,2R)-norephedrine, (1R,2R)-norpseudoephedrine, (1S,2R)-ephedrine, (1R,2R)-pseudoephedrine, (R)-p-hydroxyamphetamine, and (R)-p-hydroxymethamphetamine. The metabolites excreted 2 days after administration of 2.5-10 mg of selegiline hydrochloride amounted to 44-58% of the dose. Selegiline was metabolized by three distinct pathways: N-dealkylation, beta-carbon hydroxylation, and ring-hydroxylation. The major metabolite was (R)-methamphetamine. During metabolism, no racemic transformation occurred and beta-carbon hydroxylation showed apparently product stereoselectivity.

Adult↗

PubMed1996

Identification of a pyrovalerone metabolite in the rat by gas chromatography-mass spectrometry and determination of pyrovalerone by gas chromatography-nitrogen-phosphorus detection.

Pyrovalerone and its hydroxylated metabolite have been identified by gas chromatography-mass spectrometry in rat urine and plasma. A sensitive gas chromatographic method for the quantitative analysis of pyrovalerone in rat urine and plasma is described. The method also permits the quantitative monitoring of the urinary excretion of the drug and its metabolite. Pyrovalerone and its hydroxylated metabolite are detected up to 18 h after a single oral administration to the rat at a dose of 20 mg/kg.

Animals↗

PubMed1996

Mechanisms of murine RANTES chemokine gene induction by Newcastle disease virus.

We have previously defined the lipopolysaccharide (LPS)-responsive element (LRE) in the promoters of murine RANTES (regulated on activation normal T-cell expressed) (MuRantes) and murine IP-10/crg-2, chemokines which have potent chemotactic properties for inflammatory cells including monocytes and T lymphocytes. In the present work, we studied the transcriptional mechanism of MuRantes gene induction by virus and compared it with that of LPS in an effort to understand the host responses to virus and bacterial toxins at the molecular level. MuRantes mRNA expression is induced by Newcastle disease virus (NDV) and LPS in the RAW 264.7 macrophage cell line and peritoneal macrophages of LPS-responsive C3HeB/FeJ mice. In LPS-hyporesponsive C3H/HeJ mice, only NDV induces this chemokine gene, indicating that the pathways of transcriptional activation by NDV and LPS are not identical. Using a transient transfection assay, the minimal virus-responsive element (VRE) was localized between nt -175 and -116. The VRE contains previously defined LRE motif 1 (TCAYRCTT) and motif 3 ((T/A)GRTTTCA(G/C)TTT), which were shown to also be important for initiation of transcription by virus. NDV-stimulated nuclear extracts were tested for trans-activating factors able to bind the VRE. The chromosomal protein HMG-I(C) was shown to bind the 3'-A.T-rich domains of the VRE, and the presence of HMG-I(C) was demonstrated in the VRE-protein complex formed with nuclear extracts from NDV-stimulated, but not unstimulated cells. These findings demonstrate the role of HMG-I(C) in activation of MuRantes promoter by NDV.

Animals↗

PubMed1996

Hyaluronan fragments activate an NF-kappa B/I-kappa B alpha autoregulatory loop in murine macrophages.

Macrophages play an important role in the acute tissue inflammatory response through the release of cytokines and growth factors in response to stimuli such as lipopolysaccharide (LPS). Macrophage inflammatory effector functions are also influenced by interactions with the extracellular matrix (ECM). Such macrophage-ECM interactions may be important in regulating chronic inflammatory responses. Recent evidence has suggested that hyaluronan (HA), a glycosaminoglycan (GAG) component of ECM can induce inflammatory gene expression in murine macrophages. HA exists in its native form as a large polymer, but is found as smaller fragments under inflammatory conditions. The NF-kappa B/I-kappa B transcriptional regulatory system has been shown to be a critical component of the host inflammatory response. We examined the effects of high molecular weight HA and lower molecular weight HA fragments on NF-kappa B activation in mouse macrophages. Only the smaller HA fragments were found to activate NF-kappa B DNA binding activity. After HA stimulation, I-kappa B alpha mRNA was induced and I-kappa B alpha protein levels, which initially decreased, were restored. The induction of I-kappa Balpha expression was not observed for other GAGs. The time course of I-kappa B alpha protein regeneration in response to HA fragments was consistent with an autoregulatory mechanism. In support of this mechanism, in vitro translated murine I-kappa B alpha inhibited HA fragment-induced NF-kappa B DNA binding activity. The NF-kappa B DNA binding complex in HA-stimulated extracts was found to contain p50 and p65 subunits. Activation of the NF-kappa B/I-kappa B system in macrophages by ECM fragments may be an important mechanism for propagating the tissue inflammatory response.

Animals↗

PubMed1996

Sensitive assay for verapamil in plasma using gas-liquid chromatography with nitrogen-phosphorus detection.

A sensitive gas-chromatographic method for quantitative analysis of verapamil in human plasma is described. The method involves a single extraction procedure, followed by separation on a capillary column and detection with a nitrogen-phosphorus detector. The detection limit, based upon an assayed plasma volume of 0.5 ml, is 2 ng/ml. The standard curve is linear in the concentration range of 2 to 1000 ng/ml. The recovery of verapamil by pentane-isopropanol extraction was found to be 95%. Zipeprol is used as the internal standard. No interference from drugs needed for the associated cancer therapy has been found. Serum verapamil concentrations are determined by this method in fourteen cancer patients undergoing treatment with adriamycin.

Adult↗

PubMed1996

Spectroscopic and elemental investigation of microbial decomposition of aquatic fulvic acid in biological process of drinking water treatment.

As humic substances left in treated water tend to form trihalomethans during chlorination, their removal in water treatment processes is a significant concern for drinking water supplies. One of the removal technologies, the biofilm reactor is studied for the microbial decomposition of aquatic fulvic acid (AFA). The AFA is characterized by elemental analysis. UV-Vis, 13C-NMR, and IR spectroscopic methods. The spectroscopic and elemental investigation was capable of characterizing the microbial decomposition of AFA. Biologically treated fulvic acid was in a more oxidized state; its spectra displayed a higher degree of condensation of aromatic constituents than influent fulvic acid. Microbial degradation of AFA was more active in the low molecular weight fractions and intensively occurred in the aliphatic fraction.

Benzopyrans↗

PubMed1996

Biotransformation of uridine monophosphate (UMP) and glucose to uridine diphosphate-glucose (UDPG) by Candida saitoana KCTC7249 cells.

The present study investigates the biotransformation of glucose with uridine monophosphate (UMP) to obtain sugar nucleotide, UDP-glucose (UDPG), by the dried cells of Candida saitoana KCTC7249. The biotransformation was optimized by varying the concentrations of substrates and phosphate ion. UDPG (24 mM) was biotransformed from 200 mM glucose and 37.5 mM UMP by dried cells of C. saitoana. The glucose yields about 64% UDP-glucose, based on UMP concentration. The addition of glucose-1-phosphate to the reaction mixture accelerated the formation of UDPG from a concentration of UMP. The structure of UDP-glucose obtained was determined with 13C NMR and FAB mass spectra. These results indicate that the yeast-dried cells could be used for the production of nucleotide sugars for donor molecules of complex carbohydrate synthesis.

Candida↗

PubMed1995

A novel Bcl-2 related gene, Bfl-1, is overexpressed in stomach cancer and preferentially expressed in bone marrow.

Programmed cell death (apoptosis) is an active process which is genetically encoded and plays an important role in several cellular activities such as embryonic development, deletion of autoreactive T-cells and homeostasis. Several genes regulating apoptosis have been reported, including p53, one of the tumor suppressor genes, c-myc, one of the proto-oncogenes, and various kinds of Bcl-2 related genes. A new cDNA clone which is homologous to Bcl-2, named as Bfl-1 were isolated from a human fetal liver at 22 week of gestation. This clone was identified by computer analysis of random cDNA sequences that were obtained in an effort to expand the expressed sequence tag (EST) databases to be used for human genome analysis. The homology was recognized by 72% amino acid identity to the murine A1 gene, a member of the Bcl-2-related genes. The homology to the BH1 and BH2 domains of Bcl-2 was especially significant, suggesting that Bfl-1 is a new member of the Bcl-2-related genes. Bfl-1 is abundantly expressed in the bone marrow and at a low level in some other tissues. Interestingly, a correlation was noted between the expression level of Bfl-1 gene and the development of stomach cancer in eight sets of clinical samples. It is conceivable that Bfl-1 is involved in the promotion of the cell survival in the stomach cancer development or progression.

Amino Acid Sequence↗

PubMed1995

Regulatory mechanisms of MuRantes and CRG-2 chemokine gene induction in central nervous system glial cells by virus.

In this report we characterize the induction mechanisms of two chemokine genes, MuRantes and crg-2, the murine homologs of human RANTES and IP-10, respectively, in primary rat astrocytes and microglia by the neurotropic paramyxovirus, Newcastle Disease Virus (NDV). The time course for NDV induction of both MuRantes and crg-2 genes in astrocytes and microglia was similar, with peak mRNA expression at 10-12 h. Unlike crg-2, MuRantes mRNA was not induced by IFN-gamma. MuRantes and crg-2 are transcriptionally induced by noninfectious, UV-irradiated NDV in astrocytes and microglia, unlike TNFalpha gene transcription, which is induced only by live NDV. These data indicate that signals generated through virus-receptor interaction on the target cell surface suffice to initiate MuRantes and crg-2 gene transcription in the absence of viral replication. In astrocytes, MuRantes mRNA accumulation in response to NDV was completely blocked by tyrosine kinase inhibitors, and partially by PKC and PKA inhibitors, whereas crg-2 mRNA accumulation was significantly inhibited by PKC inhibitors, but minimally or not affected by inhibitors of tyrosine kinase or PKA activity. These kinase inhibitors also affected MuRantes and crg-2 gene transcription in similar patterns to those observed for mRNA levels, but did not reduce the mRNA stability. Therefore, the signals required for mRNA accumulation appear to operate at the level of transcription. Efficient transcription of MuRantes and crg-2 genes may require different sets of transcriptional proteins and enhancers that are regulated by different signaling pathways activated by NDV.

Amino Acid Sequence↗

PubMed1995

Construction of a gene expression profile of a human fetal liver by single-pass cDNA sequencing.

We have obtained an overall gene expression profile of a human fetal liver by sequencing the 5' ends of random cDNA clones from an unbiased cDNA library. As a result, many novel genes that might be related to liver growth and hemopoiesis have been identified. Poly (A)+ RNA was purified from the liver of a human fetus obtained at the 22nd week of gestation, and a directional library was constructed with oligo d(T)-primed cDNAs synthesized without any normalizing procedures. The 5' end of each randomly chosen clone was sequenced by the dideoxy-chain termination methods, and each sequence was used for homology search in the public databases such as GenBank, SWISS-PROT, and PIR. Of 1231 random cDNA clones analyzed, 697 clones representing 204 different transcripts (57%), were identical to previously known human genes. The spectrum of the genes in this category reflected well the physiological characteristics of the fetal liver, a combination of hepatic and hemopoietic functions. About 4% of the clones represented novel gene transcripts with significant homologies to known genes of human or other organisms. These included several genes that are known to be involved in cellular differentiation and/or proliferation. About 25% of the clones had no statistically significant match to any known genes. In summary, we have identified 546 different gene transcripts consisting of 204 known human genes, 42 homologous genes, and 300 unknown genes. Thus, this approach appears to be a highly efficient way to identify novel genes of biological interest.

Base Sequence↗

PubMed1994

Detection and identification of famprofazone and its metabolite in human urine.

Detection and identification of famprofazone and its metabolite, p-hydroxydesmethylfamprofazone, were described. The identity of the new metabolite was confirmed by comparing its mass spectrum and gas chromatographic retention time with that of the synthetic standard and its derivatives. Unchanged famprofazone was detected up to 6 h and the metabolite was detected up to 32 h in human urine after administration of famprofazone. The sum of the two compounds excreted in urine was ca. 1.5% of the dose.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1994

Single amino acid substitutions of alpha 1-antitrypsin that confer enhancement in thermal stability.

A recombinant alpha 1-antitrypsin variant which increased thermal stability was obtained from random mutagenesis followed by screening. The clone was identified as having a single mutation of Phe51-->Cys. Heat deactivation of purified recombinant alpha 1-antitrypsin produced in Escherichia coli revealed that the mutation slowed down the deactivation rate 10-fold at 57 degrees C, increasing thermal stability of recombinant protein to almost that of natural glycosylated plasma form. The mutant protein also exhibited increased stability against denaturant. The urea-induced unfolding monitored by the changes in fluorescence intensity at 360 nm showed that the mutation shifted midpoint of the transition from 1.9 M to 2.8 M. The mutation site is particularly interesting in that some genetic variants mapped at adjacent positions were shown previously to cause aggregation of the polypeptides, while the Phe51-->Cys mutation decreased aggregation rate significantly during heat deactivation. The association rate constant with porcine pancreatic elastase revealed that the mutation did not affect inhibitory activity significantly. The site identified may be critical for regulating stability of alpha 1-antitrypsin. Characterization of various single amino acid substitutions at position 51 suggests that volume and flexibility of hydrophobic side chain at the site are critical factors for enhancing the stability of alpha 1-antitrypsin.

Amino Acid Sequence↗

PubMed1994

The role of radiation treatment in management of extrahepatic biliary tract metastasis from gastric carcinoma.

PURPOSE: To determine the proper role of radiation treatment in the management of patients with extrahepatic biliary tract metastasis due to recurrent gastric cancer. METHODS AND MATERIALS: Twenty patients with malignant biliary obstruction due to recurrent gastric carcinoma after gastrectomy were treated with palliative intent at the Yonsei University College of Medicine from 1986 to 1990. Treatment consisted of external drainage alone in 11 patients (Group I) and external drainage followed by radiation treatment in nine patients (Group II). Five of nine patients in Group II underwent external irradiation in combination with intraluminal brachytherapy using high dose rate Iridium-192 (Ir-192) sources within the expandable intrabiliary prosthesis, a Gianturco stent, inserted transhepatically at the site of obstruction. RESULTS: An excellent local response was observed in five of nine patients in Group II, in whom biliary patency was restored following treatment so that the external drainage catheter could be removed. Prolongation of median survival was observed in Group II (9 months) as compared to Group I (2 months). There were no serious treatment-related complications with this approach. CONCLUSION: This treatment approach with external radiotherapy +/- intraluminal brachytherapy could achieve effective palliation and improve the quality of life in selected patients with extrahepatic biliary metastasis from gastric carcinoma.

Adult↗

PubMed1994

Definition of a lipopolysaccharide-responsive element in the 5'-flanking regions of MuRantes and crg-2.

Macrophages are stimulated by lipopolysaccharide (LPS) of gram-negative organisms. The changes in LPS-stimulated macrophages include transcriptional activation of multiple immediate-early genes, which may contribute to the natural immunity to microorganisms. We have defined by deletion and mutational analysis LPS-responsive elements (LREs) in two chemokine genes, MuRantes and crg-2, which are activated in an immediate-early manner. LRE consists of two motifs, TCAYR, which is an AP-1 half site with two flanking bases, and (A/T) (G/C)NTTYC(A/T)NTTY, which resembles in part the interferon-stimulated responsive element (ISRE). The orientation of these two motifs relative to each other in MuRantes differed from that in crg-2. These two motifs are separated by 10 and 6 nonconsensus nucleotides in the MuRantes and crg-2 LREs, respectively. Stimulation of macrophage-like RAW 264.7 cells with alpha/beta interferon did not activate MuRantes, indicating that the ISRE-like motif in MuRantes does not have ISRE activity. Upon stimulation of RAW 264.7 cells with LPS, proteins capable of binding to LRE accumulate in the nuclei as measured by electrophoretic mobility shift assay. These LRE-binding proteins include c-Jun and CREB.

Animals↗

PubMed1993

A requirement for membrane-associated phospholipase A2 in platelet cytotoxicity activated by receptors for immunoglobulin G and complement.

Platelets are potent antibody- and complement-dependent cytotoxic effector cells. We showed previously that a single platelet can lyse a target cell sensitized with immunoglobulin G (IgG) and complement components up to C3 (C integral of 3b denotes the target cell-bound fragment of complement up to C3; the precise nature of the bound C3 fragment has not been established), and that the complete cytotoxic system capable of specific recognition and lysis resides in platelet membranes. To define the components of platelet membranes required for cytotoxicity, a set of inhibitors of phospholipase A2 (PLA2) that act by different chemical mechanisms was tested. The lytic reaction is blocked at appropriate concentrations of bromophenacylbromide, mepacrine, and manoalide. When platelets are treated with bromophenacylbromide, inhibition of cytolytic activity and that of PLA2 enzymatic activity occur in parallel. Platelets release arachidonate when incubated with target cells bearing IgG and C integral of 3b, confirming that Fc gamma R and complement receptor trigger both PLA2 action and efficient lysis. Inhibition by thimerosal of a reverse reaction, i.e., reacylation catalyzed by acyltransferase, causes increased target cell lysis, presumably by increasing the products of PLA2 action. Platelet cytotoxicity is increased when platelets are pretreated with some products of PLA2: exogenous lysophospholipids and not free arachidonic acid increase cytotoxicity. Electron microscopy suggests that platelets and target cells may fuse, possibly as a result of the formation of lysophospholipids which are well-known membrane fusogens. Fixation with paraformaldehyde does not affect platelet cytotoxicity, suggesting that the complete cytotoxic system resides as a preformed complex in platelet membranes. The results indicate that platelet membrane-associated PLA2, together with receptors for Fc and complement, are required for platelet cytotoxicity.

Animals↗

PubMed1993

Cross-linking of Fc gamma RIIIA on natural killer cells results in tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2.

The Fc gamma RIIIA, which is composed of a transmembrane IgG-binding glycoprotein and either a disulfide-linked homodimer (zeta zeta, gamma gamma) or heterodimer (zeta gamma), mediates the antibody-dependent cellular cytotoxicity in NK cells. The role of phospholipase C (PLC) isozymes in Fc gamma RIIIA-mediated signal transduction was investigated. The NK cell line NK3.3 was found to contain PLC-gamma 1 and an especially high concentration of PLC-gamma 2, but PLC-beta 1 and PLC-delta 1 were not detected. Cross-linking of Fc gamma RIIIA on NK3.3 cells induced a rapid phosphorylation of PLC-gamma 1 and PLC-gamma 2 on tyrosine residues. Pretreatment of NK3.3 cells with a tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of both PLC-gamma 1 and PLC-gamma 2. These results indicate that activation of Fc gamma RIIIA on NK3.3 cells is coupled either directly or indirectly to a nonreceptor tyrosine kinase, which phosphorylates, and thereby activates PLC-gamma 1 and PLC-gamma 2.

Benzoquinones↗