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Biomedical subjects

S M Park

Publications and source records attributed to S M Park.

At least 37 records · Page 2Linked to original sources

Genotyping CagA, VacA subtype, IceA1, and BabA of Helicobacter pylori isolates from Korean patients, and their association with gastroduodenal diseases.

The genetic status of cagA, vacA subtype, iceA1, and babA, and the relationship to gastroduodenal diseases were assessed in Helicobacter pylori isolates in Korea. Seventy-six strains of H. pylori were isolated from the antrum and the corpus of 41 adult patients (22 with peptic ulcer and 19 with gastritis). The cagA, iceA1, and babA genes were assessed by polymerase chain reaction and the vacA subtypes were determined by reverse hybridization-line probe assay. The positive rates of 349-bp cagA, 208-bp cagA, iceA1, and babA genes were 97.4%, 96.1%, 84.2%, and 36.1%, respectively. The vacA s1a, s1b, s1c, and s2 variants were detected in 11.8%, 3.9%, 80.4%, and 1.3%, respectively. m1 (78.9%) is more prevalent than m2 (5.3%). The most common vacA genotype was s1c/m1 (61.9%), and 14 isolates (18.4%) contained mixed vacA genotypes from a single biopsy specimen. Twenty-one (60%) of 35 patients were infected with more than two strains of different cagA, iceA1, babA, and vacA genotypes. None of cagA, iceA1, babA, and vacA s1/m1 were associated with peptic ulcer. In conclusion, most H. pylori isolates in Korea carry cagA, iceA1, and vacA s1c/m1 genes, and reside with multiple strains. These genes do not correlate with the peptic ulcer in the Korean patients.

Adult↗

Relevance of vacA genotypes of Helicobacter pylori to cagA status and its clinical outcome.

BACKGROUND: Determination of vacA mosaicism may be important because specific Helicobacter pylori vacA genotype can be used to predict different clinical outcome. The aim of this study was to assess the relationship of vacA genotypes of Helicobacter pylori to cagA status and its development of peptic ulcer diseases in Korean patients. METHODS: Gastric biopsy specimens were obtained from 53 patients with gastric ulcer(GU), 57 with duodenal ulcer (DU) and 26 with chronic gastritis(CG) patients; all patients were infected with Helicobacter pylori. Bacterial mRNAs in the gastric mucosa were amplified by RT-PCR, using synthetic oligonucleotide primers specific for the vacA and the cagA gene. Patients with vacA s1 subtype were further examined to determine whether they had s1a or s1b subtype. RESULTS: There was no correlation in frequency of vacA s1 and/or s1a genotype between CG and either GU or DU, as the vacA s1 and s1a/m1 were present in the majority of strains independent of clinical status(s1; 100.0% versus 94.3% or 93.0% and s1a/m1; 76.9% versus 62.3% or 64.9%, respectively). Likewise, there was no difference in the prevalence of the cagA gene between CG and either GU or DU patients (92.3% versus 90.6% or 98.2%, respectively). In addition, the cagA-negative status did not predict the presence of vacA s2 genotype. CONCLUSION: These results strongly suggest that either cagA or vacA s1 and/or s1a is not proved to be a useful marker to distinguish disease-specific Helicobacter pylori strains for the development of peptic ulcer diseases in Korean patients.

Adolescent↗

Expression of mucosal cyto-chemokine mRNAs in patients with Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori-induced destruction of the gastroduodenal mucosal barrier is initiated with mucosal infiltration of inflammatory cells. Cytokines and chemokines have been suggested to play important roles in the migration and activation of these inflammatory cells into the mucosa. The present study aimed to investigate expression rates of cyto-chemokine mRNAs using gastric mucosal biopsy specimens. METHODS: In 98 patients infected with Helicobacter pylori, mucosal mRNA expression rates of cytokines (IL-1 beta, IL-6, and IL-10), C-C chemokines (macrophage inflammatory protein 1 alpha (MIP-1 alpha), and macrophage inflammatory protein 1 beta (MIP-1 beta), monocyte chemotactic and activating factor (MCAF), regulated on activation, normal T cell expressed and presumably secreted (RANTES)) and C-X-C chemokines (IL-8 and growth regulated a (GRO-alpha)) were examined using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The expression rates of mRNA for IL-8, GRO-alpha, MIP-1 alpha and RANTES were significantly more increased in H. pylori-positive patients than in H. pylori-negative patients. However, the expressions of IL-1 beta, IL-6 and IL-10 mRNA were statistically not different between two groups. After eradication of H. pylori, expressions of mRNA for three cytokines (IL-1 beta, IL-6 and IL-10), four C-C chemokines (MIP-1 alpha, MIP-1 beta, MCAF and RANTES) and two C-X-C chemokines (IL-8 and GRO-alpha) were significantly decreased. CONCLUSION: These results suggest that C-X-C chemokines and some C-C chemokines play important roles in H. pylori-associated peptic ulcer diseases.

Adult↗

Is cholecystectomy necessary after ERCP for bile duct stones in patients with gallbladder in situ?

BACKGROUND: The requirement for subsequent cholecystectomy in patients with gallbladder in situ after endoscopic removal of stones from the common bile duct (CBD) is controversial. The aims of this study were to assess the requirement for subsequent cholecystectomy for gallbladder-related symptoms, and to identify the patients who develop symptoms after the endoscopic removal of CBD stones. METHODS: Of 241 patients with gallbladder in situ following endoscopic removal of stones from the CBD, 146 patients (78 men and 68 women; mean age 69 +/- 13 years, range 20-93) with a follow-up time of more than three months without elective cholecystectomy were enrolled in the study. Fifty-nine patients had gallbladder stones (single stones in 27 and multiple stones in 32) and 87 patients had gallbladder in situ without stones. The time from entry to the occurrences of death or cholecystectomy was evaluated retrospectively. Cox regression analysis was used to evaluate the risk factors associated with these events. RESULTS: The mean duration of follow-up was 24.1 +/- 18.0 months (range 3-70 months). During follow-up, seven patients (4.8%) underwent cholecystectomy, on average 18.4 months after CBD stone removal, as the result of acute cholecystitis in four cases, biliary pain in two cases and acute pancreatitis in one case. Laparoscopic cholecystectomy was performed in four patients and open cholecystectomy in three patients. Post-operative morbidity occurred in two patients, with improvement after conservative management. Nine patients (6.2%) died as the result of unrelated biliary disease. Age, sex, presence of gallbladder stones, multiplicity of gallbladder stones and underlying disease did not correlate with subsequent cholecystectomy by Cox regression analysis. CONCLUSION: Elective cholecystectomy is not warranted in patients with bile duct stones when the common duct can be cleared of stones by endoscopic sphincterotomy. We could not find any clinical predictors of further symptoms or complications arising from the retained gallbladder.

Adult↗

High temperature stress resistance of Escherichia coli induced by a tobacco class I low molecular weight heat-shock protein.

TLHS1 is a class I low molecular weight heat-shock protein (LMW HSP) of tobacco (Nicotiana tabacum). For a functional study of TLHS1, a recombinant DNA coding for TLHS1 with a hexahistidine tag at the amino-terminus was constructed and expressed in Escherichia coli. An expressed fusion protein, H6TLHS1, was purified using a Ni2+ affinity column and a Sephacryl S400 HR column. A polyclonal antibody against H6TLHS1 was produced to follow the fate of H6TLHS1 in E. coli. The fusion protein in E. coli maintained its solubility at a temperature of up to 90 degrees C and most of the proteins in the E. coli cell lysate with H6TLHS1 were prevented from thermally induced aggregation at up to 90 degrees C. We compared the viability of E. coli cells expressing H6TLHS1 to the E. coli cells without H6TLHS1 at a temperature of 50 degrees C. After 8 h of high temperature treatment, E. coli cells with H6TLHS1 survived about three thousand times more than the bacterial cells without H6TLHS1. These results showed that a plant class I LMW HSP, TLHS1, can protect proteins of E. coli from heat denaturation, which could lead to a higher survival rate of the bacterial cells at high temperature.

Cloning, Molecular↗

Activation of the insulin-like growth factor II transcription by aflatoxin B1 induced p53 mutant 249 is caused by activation of transcription complexes; implications for a gain-of-function during the formation of hepatocellular carcinoma.

Aflatoxin B1 (AFB1) induced mutation of the p53 gene at codon 249 (p53mt249) is critical during the formation of hepatocellular carcinoma (HCC) following hepatitis B virus (HBV) infection. p53mt249 markedly increases insulin-like growth factor II (IGF-II) transcription largely from promoter 4, accumulating the fetal form of IGF-II. Modulation of the transcription factor binding to IGF-II P4 by wild-type p53 and p53mt249 was identified. Wild-type p53 inhibited binding of transcription factors Sp1 and TBP on the P4 promoter, while p53mt249 enhanced the formation of transcriptional complexes through enhanced DNA-protein (Sp1 or TBP) and protein-protein (Sp1 and TBP) interactions. p53mt249 stimulates transcription factor Sp1 phosphorylation which might be a cause of increased transcription factor binding on the P4 promoter while wild-type p53 does not. Transfection of hepatocytes with p53mt249 impaired induction of apoptosis by the HBV-X protein and TNF-alpha. Therefore, the blocking of apoptosis through enhanced production of IGF-II should provide a favorable opportunity for the selection of transformed hepatocytes. These results explain the molecular basis for the genesis of HCC by p53mt249 which was found to be induced by a potent mutagen, AFB1.

Aflatoxin B1↗

Comparative study of Korean (Viscum album var. coloratum) and European mistletoes (Viscum album).

A lectin (agglutinin, VCA) from Korean mistletoe (Viscum album L. coloratum) was isolated by affinity chromatograpy on a asialofetuin-Sepharose 4B. The molecular weights of A- and B-chains of VCA were differenf from those of VAAS. The VCA recognized the antibody of VAAs in the Western blot analysis and ELLA system. We also investigated the synergistic effects of the components in mistletoe by dividing the extract into different molecular weight fractions.

Antineoplastic Agents, Phytogenic↗

Effect of extracellular cations on the chemotherapeutic efficacy of anticancer drugs.

Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcemia. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined by cell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important role in the therapeutic activities of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic doses of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.

Antineoplastic Agents↗

Comparing MR imaging and CT in the staging of gastric carcinoma.

OBJECTIVE: The purpose of this study was to assess the usefulness of breath-hold two-dimensional (2D) fast low-angle shot (FLASH) and T2-weighted turbo spin-echo fast MR imaging compared with helical CT in the staging of gastric carcinoma. SUBJECTS AND METHODS: Thirty patients with gastric carcinoma underwent preoperative MR imaging and helical CT. MR imaging at 1.5 T was performed immediately after the intramuscular injection of scopolamine and the oral administration of water or effervescent granules. Breath-hold 2D FLASH T1-weighted images in all three planes, turbo spin-echo T2-weighted axial images, and gadolinium-enhanced fat-suppressed 2D FLASH axial images were included. Helical CT was performed 60 sec after initiation of i.v. contrast medium injection (2.5-3 ml/sec). Two groups of two radiologists each independently analyzed the MR and helical CT findings, and these results were compared with the pathologic findings. RESULTS: For T staging, MR imaging accuracy was higher than that of helical CT (73.3% and 66.7%, respectively); however, the accuracies of the two methods were not significantly different from each other (McNemar test, p > 0.05). Overstaging was noted in 6.7% of cases with MR imaging and 10% with helical CT. Understaging was noted in 20% of cases with MR imaging and 23.3% with helical CT. For N staging, the accuracies of MR imaging and helical CT were 55% and 58.6%, respectively, with no statistical significance (overstaging, 10% and 6.9%; understaging, 34.5% and 34.5%, respectively). CONCLUSION: MR imaging was comparable to helical CT in the T and N staging of gastric cancer.

Adult↗

Systemic mononuclear inflammatory vasculopathy associated with Sjögren's syndrome in a patient with primary biliary cirrhosis.

We report a 46-year-old woman with primary biliary cirrhosis (PBC) presenting with Sjögren's syndrome and systemic mononuclear inflammatory vasculopathy. Biopsy specimens of sural nerve showed findings consistent with vasculitic neuropathy. Perivascular inflammatory mononuclear cell infiltration was observed on muscle biopsy specimen. The findings of abdominal computed tomography and brain magnetic resonance imaging were suggestive of vasculitis. Clinical manifestations and radiologic findings were improved after high dose prednisolone therapy.

Biopsy, Needle↗

Radicicol suppresses expression of inducible nitric-oxide synthase by blocking p38 kinase and nuclear factor-kappaB/Rel in lipopolysaccharide-stimulated macrophages.

We show that radicicol, a fungal antibiotic, produces a marked inhibition of p38 kinase, nuclear factor-kappaB/Rel (NF-kappaB/Rel), and inducible nitric-oxide synthase (iNOS) transcription by the macrophage line RAW 264.7 in response to lipopolysaccharide (LPS). Treatment of RAW 264.7 with radicicol inhibited LPS-stimulated p38 kinase phosphorylation in a dose-related manner. iNOS transcription, which is regulated in part by the NF-kappaB/Rel family of transcription factors, has been shown to be under the control of the p38 kinase signaling cascade. Our data also show that the p38 kinase pathway is specifically involved in LPS-induced NF-kappaB/Rel activation and iNOS expression because NF-kappaB/Rel DNA binding and iNOS mRNA production in the presence of a specific inhibitor of p38 kinase, SB203580, were dramatically diminished. In contrast, PD98059, a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase 1 had no effect on NF-kappaB/Rel activation and iNOS expression. LPS-induced loss of inhibitory proteins IkappaB-alpha and IkappaB-beta and translocation of p65, c-Rel, and p50 was inhibited by radicicol. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking p38 kinase signaling. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of radicicol on iNOS suggest that this potent antifungal agent may represent a useful anti-inflammatory agent.

Animals↗

Differential induction of cytokine genes and activation of mitogen-activated protein kinase family by soluble CD40 ligand and TNF in a human follicular dendritic cell line.

Follicular dendritic cells (FDC)3 play crucial roles in germinal center (GC) formation and differentiation of GC B cells. Many aspects of FDC function are influenced by contact with B or T cells, and by cytokines produced in the GC, which involve stimulation of CD40 and TNF-alpha receptors on FDC. In this study, using an established FDC line, HK cells, we compared the effects of CD40 and TNF receptor triggering on cytokine induction and activation of mitogen-activated protein kinase family. We show that HK cells spontaneously produced IL-6, M-CSF, and G-CSF mRNA. Both the soluble form of CD40 ligand (sCD40L) and TNF increased the level of M-CSF and G-CSF mRNA. While TNF strongly induced IL-6 mRNA, its expression was not affected by sCD40L treatment, differing from the strong IL-6 induction in other cell types upon CD40 stimulation. In addition, sCD40L treatment resulted in activation of extracellular signal-related kinase 1 and 2 (ERK1/2) and p38 without significant increase in c-Jun N-terminal kinase (JNK) activity. Lack of JNK activation differs in that most B cells respond to CD40 stimulation by inducing JNK activity strongly, suggesting distinct characteristics of CD40 signaling in FDC. Compared with the effects of sCD40L, TNF was capable of inducing JNK activity in addition to the activation of ERK1/2 and p38. Furthermore, the proximal signaling elements activated by TNF differed from those activated by sCD40L, in that TNF did not require PMA-sensitive protein kinase C isoforms in the activation of ERK and p38, whereas sCD40L did. However, signals activated by these stimuli converged on cytokine gene expression in a synergistic manner, which may have implication in augmenting FDC function during GC reaction.

CD40 Antigens↗

Metabolite and isotopomer balancing in the analysis of metabolic cycles: II. Applications.

In a previous paper (Klapa et al., 1999), we presented a model for the analysis of isotopomer distributions of the TCA cycle intermediates resulting from 13C (or 14C) labeling experiments. Results allow the rigorous determination of the degree of enrichment at specific carbon atoms of metabolites, of the molecular weight distribution of metabolite isotopomers, as well as of the fine structure of NMR spectra in terms of a small number of metabolic fluxes. In this paper we validate the model by comparing model predictions with experimental data and then apply it to the analysis of metabolic networks that have been investigated in previous studies. The results have allowed us to conclude that: (1) there is no evidence of propionyl-CoA carboxylase pathway in Escherichia coli; and (2) the possibility that acetone utilization in mammals occurs solely via the "lactate/methylglyoxal" pathway is consistent with available labeling data. The presented modeling framework provides additional constraints that must be satisfied by experimental data in a biochemical network structure and therefore enhances the power of labeling methods for resolving in vivo metabolic fluxes.

Acetic Acid↗

A novel parvovirus isolated from Manchurian chipmunks.

A novel parvovirus was identified in Manchurian chipmunks inhabiting Korea. Hepatitis B surface antigen (HBsAg) was detected in sera from 4 animals among 62 apparently healthy chipmunks. Electron microscopic examination of the HBsAg-positive sera revealed virus-like spherical particles 20-22 nm in diameter. Extraction of nucleic acid under annealing conditions from the serum samples containing virus-like particles yielded a single species of DNA molecule with the electrophoretic mobility of 5.6-kb double-stranded DNA. Four overlapping clones that encompassed almost the full-length viral genome, except both ends, were obtained. By sequencing these clones, we determined the sequence of 5097 nucleotides of the viral DNA. Two open reading frames were identified, with the left side open reading frame encoding a putative nonstructural protein and the right side open reading frame encoding a putative capsid protein. The nucleotide and amino acid sequences showed significant homology to parvovirus B19 and simian parvovirus, but showed little homology to other mammalian autonomous parvoviruses or adeno-associated viruses. These observations indicate that the virus isolated from Manchurian chipmunks is a novel parvovirus and may be a potentially useful animal model of human B19 infection as a new member of the Erythrovirus genus of the Parvoviridae.

Amino Acid Sequence↗

Effect of Helicobacter pylori infection on antral gastrin and somatostatin cells and on serum gastrin concentrations.

OBJECTIVES: Helicobacter pylori infection induces selective reduction of the number of antral D-cells and results in abnormal regulation of serum gastrin secretion. The purpose of this study was to investigate the relationship between H. pylori infection and the numbers of G-cells and D-cells. METHODS: The numbers of antral G-cells and D-cells, the ratio of G-cells to D-cells and fasting serum gastrin concentrations were compared between 37 patients with (29 with duodenal ulcers and 8 with gastric ulcers) and 33 without H. pylori infection (22 with duodenal ulcers and 11 with gastric ulcers). Serum gastrin concentrations were measured using the radioimmunoassay technique. Antral mucosal biopsy specimens were examined using immunohistochemical staining with antibodies specific for gastrin and somatostatin and the numbers of G-cells and D-cells per gastric gland were counted. RESULTS: Fasting serum gastrin concentrations were significantly higher in patients with H. pylori infection compared to patients without infection (80.3 +/- 23.5 vs 47.6 +/- 14.1 pg/ml, p < 0.001). The number of G-cells per gastric gland was similar in infected and uninfected patients (7.1 +/- 3.1 vs 7.3 +/- 3.9, respectively, p > 0.5). The number of D-cells was significantly lower in patients with H. pylori infection than in uninfected patients in both duodenal and gastric ulcer patients (1.3 +/- 0.4 vs 2.5 +/- 1.6, respectively, p < 0.001). The ratio of G-cells to D-cells was also significantly higher in infected patients compared with uninfected patients for both gastric and duodenal ulcers (5.7 +/- 2.7 vs 3.5 +/- 1.9, respectively, p < 0.001). CONCLUSIONS: These results strongly suggest that Helicobacter pylori infection induces reduction of the number of antral D-cells. The resulting relative hypofunction of the inhibitory action of D-cells against G-cells may be responsible for increased serum gastrin secretion.

Case-Control Studies↗

Assessment of body composition using dual energy x-ray absorptiometry in patients with liver cirrhosis: comparison with anthropometry.

OBJECTIVES: The aim of this study was to evaluate changes of body composition in cirrhotic patients. Dual energy x-ray absorptiometry (DEXA) and anthropometry were used, and the values obtained were compared. METHODS: Mid-arm fat and muscle areas were calculated by anthropometry in 66 cirrhotic patients and 94 healthy controls. In 37 of the cirrhotic patients and 39 of the controls, fat mass, lean soft tissue mass and bone mineral contents were measured with DEXA. RESULTS: The number of cirrhotic patients with measured values below the fifth percentile of normal controls was 21 (31.8%) by mid-arm fat area, six (9.1%) by mid-arm muscle area, 15 (40.5%) by fat mass and 0 (0%) by lean soft tissue mass. The fat mass in cirrhotic patients was less than in controls, whereas lean soft tissue mass and bone mineral content were not different. Fat depletion was severe in Child-class C patients and with severe ascites. Mid-arm fat area and fat mass showed close correlation (r = 0.85, p < 0.01), but mid-arm muscle area and lean soft tissue mass showed poor correlation (r = 0.32, p < 0.05). CONCLUSION: Cirrhotic patients showed lower fat component, with preserved lean soft tissue mass and bone mineral content. In clinical practice, the measurement of mid-arm fat area was useful for the assessment of fat mass.

Absorptiometry, Photon↗

Comparison of the structure and expression pattern for a low molecular weight heat-shock protein cDNA clone from Nicotiana tabacum.

We isolated a cDNA clone, named TLHS-1, for a low molecular weight heat-shock protein (LMW HSP) from tobacco. The nucleotide sequence determination of the clone identified an open reading frame for 159 amino acids. To the upstream of the open reading frame, a sequence of 124 nucleotides was determined. To the 3' downstream of the open reading frame, 212 nucleotides were identified which carried a poly(A) tail. A comparison of the open reading frame of TLHS-1 with the previously reported class I LMW HSPs showed a high identity which classified the TLHS-1 as a class I LMW HSP cDNA clone. Reexamination of the amino acid sequences for LMW HSPs including the TLHS-1 argued for the necessity to redraw the consensus region. Six consensus regions were proposed instead of the two consensus regions suggested previously. A RNA blot hybridization for TLHS-1 showed the typical expression pattern of a heat-shock inducible gene from 3 common tobacco cultivars. The genomic DNA blot hybridization for the TLHS-1 gene from the 3 tobacco cultivars showed identical patterns. These results implied that the expression control and structure of the TLHS-1 gene have been well conserved in the tobacco cultivars which are not bred for high temperature stress resistance.

Amino Acid Sequence↗