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Biomedical subjects

H Song

Publications and source records attributed to H Song.

At least 73 records · Page 4Linked to original sources
PubMed2000

Ambient sulfate concentration and chronic disease mortality in Beijing.

In this study, ecological analysis was used to assess the relationship between ambient air pollution and human mortality. All the data on environmental measures and related factors, population size and number of deaths were collected for the city of Beijing, PR China and its eight districts for the years 1980-1992. In this study the concentration of SO(4)2- was selected as a main indicator of environmental pollution for the following reasons: (i) SO(4)2- data are available to cover all urban and suburban areas in Beijing compared with other air pollutants during the study period; (ii) SO(4)2- levels indicate the concentration of sulfide (include sulfate) and acid fog in the air, and they are significantly lower in cleaner districts than in others; and (iii) analyses showed that SO(4)2- levels are significantly correlated with daily mean concentrations of sulfur dioxide and nitrogen oxide, annual coal combustion, number of households using gas fuel, counts of motor vehicles and population density. Age-standardised mortality rates due to specific diseases were calculated using the Chinese population census data in 1990. Statistically significant correlations were observed between SO(4)2- concentration and total mortality and mortality due to cardiovascular disease, malignant tumour and lung cancer (r > 0.50 in all cases). The correlations were not only found between the current SO(4)2- concentration and these mortalities, but also for SO(4)2- levels measured up to 12 years prior to death, which may suggest long-term effects of air pollution. No significant correlations were observed for mortality from respiratory diseases and cerebrovascular diseases (r = 0.30-0.50). This study indicates that the concentration of SO(4)2- in air is a useful air pollution indicator in the areas where coal is used as the main source of energy. Areas with high levels of SO(4)2- experienced higher mortality due to a variety of chronic diseases.

Air Pollutants↗
PubMed2000

Tamoxifen-induced enhancement of calcium signaling in glioma and MCF-7 breast cancer cells.

The antiestrogen tamoxifen is commonly used to treat breast cancer, but it also has therapeutic activity in several other types of cancer. Many of these tumors, including malignant gliomas, are estrogen receptor negative. Nonetheless, high concentrations of tamoxifen can directly reduce cell proliferation in some of these tumors and induce apoptosis. In this study, the role of tamoxifen in calcium signaling and calcium-induced cell death was studied in both malignant glioma cell lines and MCF-7 breast cancer cells. Tamoxifen potently increased the spatial expansion of calcium waves by 30-150% while significantly enhancing and prolonging agonist-induced calcium elevations. Furthermore, tamoxifen pretreatment accelerated calcium ionophore-induced death by more than 20 min, suggesting that tamoxifen lowered cellular resistance to calcium loads. In contrast to its potentiating of calcium signaling in tumors, tamoxifen had no significant effect on calcium signaling in cultures of primary astrocytes from either human or rat brain. This study demonstrates the existence of calcium signaling in breast cancer and glioma cells and identifies tamoxifen as a potential modulator of tumor-associated calcium signaling.

Adenosine Triphosphate↗
PubMed2000

Simultaneous determination of a novel thrombin inhibitor and its two metabolites in human plasma by liquid chromatography/tandem mass spectrometry.

I, 3-(2-phenethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylene-c arboxamidomethylpyridinyl)-pyrazinone dihydrochloride monohydrate, is a potent, orally active thrombin inhibitor. The compound also has two metabolites which have been shown to have thrombin inhibitory activity: benzylic alcohol M3 metabolite (II) and hydroxymethylpyrazinone M7 metabolite (III). A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous determination of I and its two metabolites in human plasma has successfully been developed. The method consists of treating 0.5 ml plasma with 2 N NaOH and extracting I, II, III and internal standard (IV) with ethyl acetate:methyl-t-butyl ether (1:3, v/v). The analytes were then back-extracted into 2% formic acid. The analytes were chromatographed by high performance liquid chromatography (HPLC) and detected by MS/MS. Positive ionization was used on a heated nebulizer probe monitoring precursor --> product ion combinations in multiple reaction monitoring mode. The linear range is 0.5-1000 nM for I and III and 0.75-1000 nM for II. Recoveries were 88, 74, 78 and 102.1% for I, II and III and the internal standard, respectively in human plasma. Intraday variation using this method was < or = 7.9% for I, < or = 9.0%, for II and < or = 9.5% for III across the standard curve range. This method exhibits good linearity and reproducibility for the three analytes.

Chromatography, High Pressure Liquid↗
PubMed2000

Interconversion between µ-eta(2),eta(2)-C(60) and µ(3)-eta(2),eta(2),eta(2)-C(60) on a Carbido Pentaosmium Cluster Framework We are grateful to the Korea Science Engineering Foundation (KOSEF) for financial support (project no. 1999-1-122-001-5) of this research and a postdoctoral fellowship to K.L. The X-ray diffraction studies were carried out at the X-ray Crystallographic Laboratory of Yonsei University, which was supported in part by KOSEF.

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Journal Article↗
PubMed2000

Endogenous interleukin-18 modulates immune escape of murine melanoma cells by regulating the expression of Fas ligand and reactive oxygen intermediates.

It has been known that melanoma cells can suppress the immune system by the Fas ligand. The present study investigated whether interleukin (IL)-18, which can enhance Fas ligand expression, is produced by B16F10 melanoma cells and is involved in immune escape of tumor cells. Immunohistology, reverse transcription-PCR, intracellular fluorescence-activated cell-sorting analysis, and immunoblotting demonstrated that melanoma cells express IL-18. C57BL/6 splenocytes cultured with culture supernatants of B16F10 melanoma cells enhanced IFN-gamma production, which was blocked by anti-IL-18 antibody, indicating that IL-18 in the culture supernatants is functional. In addition to IL-18, the IL-18 receptor was also detected in B16F10 melanoma cells, suggesting a role of this cytokine in regulating the functions of B16F10 melanoma cells. The functional effect of IL-18 on B16F10 melanoma cells was shown by reduction of Fas ligand expression in cells treated with anti-IL-18 antibody or transfected with IL-18 antisense cDNA. In addition, the same treatments decreased intracellular reactive oxygen intermediate levels in B16F10 melanoma cells, indicating that IL-18 regulates reactive oxygen intermediate production, which is involved in Fas ligand expression. Furthermore, transfection of IL-18 antisense cDNA into melanoma cells increased the susceptibility of tumor cells to natural killer cells in vitro. When IL-18 antisense transfectants were implanted into syngeneic mice, severe reduction of tumor cell growth was observed with concomitant infiltrated natural killer cells in the tumor area. Taken together, these results demonstrate that IL-18 has a critical role as a survival factor for B16F10 melanoma cells.

Animals↗
PubMed2000

The crystal structure of human eukaryotic release factor eRF1--mechanism of stop codon recognition and peptidyl-tRNA hydrolysis.

The release factor eRF1 terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase center. The crystal structure of human eRF1 to 2.8 A resolution, combined with mutagenesis analyses of the universal GGQ motif, reveals the molecular mechanism of release factor activity. The overall shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl transferase center. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site.

Amino Acid Sequence↗
PubMed2000

Determination of a novel thrombin inhibitor in human plasma and urine utilizing liquid chromatography with tandem mass spectrometric and ultraviolet detection.

An LC-MS-MS method and an HPLC-UV method have been developed for the assay of a novel thrombin inhibitor in human fluids. The LC-MS-MS method is developed for plasma, which usually requires maximum sensitivity. The HPLC-UV method is for urine. In both methods, analytes are extracted using liquid-liquid extraction, and analyzed by reversed-phase high-performance liquid chromatography. A tandem mass spectrometer in the multiple reaction monitoring (MRM) mode is used for detection of the analytes in the plasma method. UV is the detector for the urine method. The plasma method has a lower limit of quantitation (LOQ) of 0.1 ng/ml with a linearity range of 0.1-100 ng/ml. The urine method has an LOQ of 8.12 ng/ml (20 nM) and the linear dynamic range is 8.12-8120 ng/ml (20-20000 nM). Both methods are fast, specific and sensitive. Various validation procedures have proven that both methods are rugged, robust and reproducible. The research also suggested that, while LC-MS-MS provides superior sensitivity and selectivity for the determination of drugs and their metabolites at very low concentrations, HPLC with a conventional detector such as UV is still useful in the analysis when the sensitivity requirement is not crucial.

Chromatography, Liquid↗
PubMed2000

Determination of resibufogenin and cinobufagin in heart-protecting musk pill by HPLC.

A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of resibufogenin and cinobufagin in traditional Chinese medicine (heart-protecting musk pill, shexiang baoxin wan in Chinese) was developed. A reversed-phase system with a Hypersil (ODS2) C(18) column and tetrahydrofuran: methanol: water (8:31:61) mobile phase was employed for the separation of resibufogenin and cinobufagin. The detection was set at 299 nm and ethinyl estradiol was chosen as the internal standard. The limit of detection was 1.5 ng for resibufogenin and 2.0 ng for cinobufagin at a signal-to-noise ratio of 4:1. It is a rapid, simple and accurate method for quantitative analysis of resibufogenin and cinobufagin in heart-protecting musk pill.

Bufanolides↗
PubMed2000

A novel heparin/protamine-based pro-drug type delivery system for protease drugs.

Previously we proposed a heparin/protamine-based system for delivery of protease drugs such as tissue-specific plasminogen activator (tPA). To demonstrate the feasibility of this approach as well as its pro-drug and triggered release features, positively charged peptides [(Arg)(7)Cys] were successfully linked to tissue-specific plasminogen activator (tPA) using the crosslinking agent N-succinimidyl-3-(2-pyridyldithio)- propionate. This cation-modified tPA showed much stronger heparin affinity than the parent tPA. The complex formed by mtPA and heparin was stable in human plasma, and the activity of mtPA in such a complex was inhibited by the appended heparin. Similarly, the activity of mtPA could also be inhibited by a heparin-antifibrin IgG conjugate in which heparin was linked, via endpoint attachment, to the sugar moieties in the F(c) region of anti-fibrin IgG. Aside from this pro-drug feature exhibited by the binding of the macromolecule heparin to mtPA, results from chromogenic and in vitro clot lysis assay demonstrated that the heparin-induced inhibition of the mtPA activity could be easily reversed by the addition of an adequate amount of protamine. These findings suggest the applicability of the heparin/protamine delivery system to abort the potential bleeding risks associated with clinical use of tPA. In addition to the chemical conjugation method, modified tPA could also be produced by the recombinant DNA method. The expressed modified tPA (EmtPA) thus prepared retained the full catalytic activity of the parent tPA, and this activity could also be inhibited by heparin, and the heparin-induced inhibition could be reversed following the addition of protamine.

Drug Carriers↗
PubMed2000

Glomerulosclerosis in adriamycin-induced nephrosis is accelerated by a lipid-rich diet.

The present study was performed to determine quantitatively the effect of hypercholesterolemia induced by a lipid-rich diet on glomerulosclerosis in an animal model of nephrotic syndrome (NS) induced by Adriamycin (ADR). Twenty NS Wistar rats administered ADR with a single intravenous dose of 5 mg/kg body weight were divided into standard and lipid-rich chow groups. Another 20 weight-matched non-NS rats that received a vehicle alone were grouped as controls. Quantitative analyses of renal histological changes were performed with determination of blood and urine biochemical parameters. It was found that serum cholesterol was markedly higher in rats with lipid-rich chow in both NS and non-NS rats. Urinary protein was significantly higher in rats on the lipid-rich diet in the NS group. The mesangial matrix and cell indices were significantly increased in rats with the lipid-rich diet and the most obvious changes were found in the NS group. Lipid deposits and foam cells were observed in mesangial areas, and some glomeruli had progressed to form focal and segmental glomerulosclerosis in the NS group. Findings indicated that diet-induced hyperlipidemia can lead to proliferation of mesangial cells and accumulation of mesangial matrices, and further aggravate glomerulosclerosis in Adriamycin-induced nephrosis.

Animals↗
PubMed2000

Routine minimally invasive aortic valve procedures.

BACKGROUND: Due to the lack of objective evidence supporting the advantages and early technical difficulties, minimally invasive aortic valve procedures were performed on a highly selective rather than routine basis. METHODS: From September 1997 to February 1999, one surgeon routinely used upper or transverse minimally invasive sternotomy to perform 46 consecutive cases of aortic valve procedures (M), whereas two other surgeons performed 40 aortic valve procedures through a conventional sternotomy (C). RESULTS: More time consuming and technically demanding surgeries were done in M. There was one death in each group. Aortic clamp time was longer in M (93+/-40 vs 59+/-24 min, P=0.001). There were no differences in operating time, pump time, intubation duration, bleeding and intensive care unit stay. The advantages of minimally invasive aortic valve operation included better postoperative ejection fraction (58+/-17 vs 51+/-10%, P=0.04), decreased pain score (3+/-2 vs 5+/-2, P=0.004), less transfusion (19 vs 55%, P=0.02), shorter duration of chest tube drainage, and cosmetically more acceptable surgical wound (6.8+/-2.2 vs 5.2+/-2.0, P=0.018). From our series, we could not find any negative effects of minimal access surgery. CONCLUSIONS: Our study demonstrated that aortic valve surgeries could be performed routinely by the minimally invasive approach with a high degree of effectiveness and safety.

Adolescent↗
PubMed2000

Identification of the gene for a novel liver-related putative tumor suppressor at a high-frequency loss of heterozygosity region of chromosome 8p23 in human hepatocellular carcinoma.

Human chromosome 8p23 is known as a region that is associated with loss of heterozygosity (LOH), which is frequently deleted in hepatocellular carcinoma (HCC) tissues. We report here the characterization of a gene for a liver-related putative tumor suppressor (LPTS) localized at 8p23, that was isolated by allelic-loss mapping and positional candidate cloning. The expression of the gene for LPTS was ubiquitous in normal human tissues, albeit at relatively low levels, whereas levels appeared to be significantly reduced, or sometimes undetectable in HCC cells and neoplastic tissues. Thus, it appeared that LPTS might be involved in the control of cell proliferation. Indeed, we observed the significant suppression of growth and growth arrest of SMMC-7721 HCC cells after introduction of the gene for LPTS. We also used antisense oligodeoxynucleotides (AS-ODNs) to suppress the expression of LPTS in normal liver cells L02. Several AS-ODNs specific for LPTS mRNA significantly enhanced cell growth, whereas control oligodeoxynucleotides (ODNs) did not. Our results suggest that LPTS might be a growth-inhibitory protein in human hepatocytes.

Amino Acid Sequence↗
PubMed2000

Expression of vascular cell adhesion molecule-1, alpha4-integrin and L-selectin during inner ear immunity reaction.

The expression of vascular cell adhesion molecule-1 (VCAM-1), alpha4-integrin and L-selectin was dynamically observed using an immunohistochemical approach during labyrinthitis induced by inoculation of keyhole limpet hemocyanin into the scala tympani of animals that had been systemically sensitized to it. At the same time, we used ELISA to monitor interleukin-1(IL-1) in the peripheral blood of these animals. The expression of alpha4-integrin and L-selectin on the surface of leukocytes in peripheral blood was examined by flow cytometry. VCAM-1 was found on the endothelial surface of the spiral modiolar vein (SMV) and its collecting venules (CV) at 24 h post-challenge; the VCAM-1 level reached a maximum on day 2, which was maintained until 1 week post-challenge, and then declined gradually. Alpha4-integrin was found on the surface of leukocytes, mainly monocytes and lymphocytes, that had infiltrated the SMV, CV, cochlear nerve and perilymph by 24 h post-challenge; the alpha4-integrin level reached a maximum on day 2 and then decreased rapidly. At 1 week post-challenge, no significant expression of alpha4-integrin was seen. Expression of alpha4-integrin and L-selectin was also observed on leukocytes in peripheral blood. No L-selectin was observed on the surface of leukocytes during inner ear inflammation. The expression of L-selectin on the surface of leukocytes in the peripheral blood appeared to be downregulated during inflammation. The concentrations of IL-1 in the peripheral blood increased commensurately during inner ear inflammation. These results further elucidate the role of adhesion molecules during inner ear immune responses. The increased expression of VCAM-1 on SMV and CV was correlated with the concentration of IL-1 in peripheral blood during inner ear inflammation.

Animals↗
PubMed2000

Comparison of Tc-99m sestamibi, serum neuron-specific enolase and lactate dehydrogenase as predictors of response to chemotherapy in small cell lung cancer.

Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are tumor markers of small cell lung cancer (SCLC) which were reported to predict outcome of patients with SCLC. We previously reported that dipyridamole-modulated Tc-99m sestamibi (dipyridamole-MIBI) single photon emission computed tomography (SPECT) could predict the response to chemotherapy in SCLC patients. The purpose of this study was to compare dipyridamole-MIBI and pretreatment serum levels of NSE and LDH for the prediction of response to chemotherapy in SCLC. Twenty-eight SCLC patients underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at lease two cycles). Serum levels of NSE and LDH were also measured at the same day of the imaging. Tomographic images before and after 0.84 mg/kg dipyridamole infusion were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete (CR), partial response (PR), no change (NC), and progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. Among the 28 patients, 15 were responders (2 CR, 13 PR) and 13 were nonresponders (11 NC, 2 PD). The change of tumor-to-normal lung ratio (T:NL) after infusion of dipyridamole was significantly higher in responders as compared with nonresponders (0.38 +/- 0.64 vs. -0.38 +/- 0.50, respectively, p = 0.002). However, pretreatment serum NSE and LDH levels did not correlate with the response to chemotherapy. Increase of T:NL after dipyridamole infusion was a strong negative predictor of chemotherapeutic response in SCLC patients, while NSE and LDH could not predict it.

Aged↗
PubMed2000

Interpretation of Wada memory test for lateralization of seizure focus by use of (99m)technetium-HMPAO SPECT.

PURPOSE: Although the intracarotid amobarbital procedure (IAP) or Wada test is useful in lateralizing seizure focus in patients with temporal lobe epilepsy (TLE), the results of the IAP memory test are frequently nonlateralizing. An insufficient suppression of the medial temporal region contralateral to the seizure focus may contribute to the failure of lateralization. We tried to correlate IAP memory results with the functional changes in the contralateral medial temporal region as measured by single photon emission computed tomography (SPECT) during IAP. METHODS: We performed a (99m)technetium-(Tc) hexamethylene-propylene-amine-oxime (HMPAO) brain SPECT in 19 medial TLE patients during a contralateral IAP (sodium amobarbital injected contralateral to the seizure focus). Regional cerebral blood flow (rCBF) was measured in the contralateral medial temporal region. The amount of decrease in the rCBF was calculated by subtracting the previous measurement from the one obtained with the interictal SPECT. RESULTS: Ten (53%) patients passed and nine (47%) failed the contralateral IAP. The mean percentage decrease in rCBF was 5.3+/-5.3%. There was a significant negative correlation between a decrease in the rCBF and the IAP memory-retention score by Spearman correlation (p = -0.53: p<0.021). Patients with smaller decreases in rCBF (<5%) more frequently passed the contralateral IAP memory test than did those with larger decreases (80 vs. 22%; p<0.023). CONCLUSIONS: We suggest that an insufficient suppression of the contralateral medial temporal function is partly responsible for nonlateralizing IAP memory tests. An IAP-SPECT may be useful in interpreting IAP memory tests for the lateralization of seizure focus in TLE patients.

Adult↗
PubMed2000

Dysregulation of EGF family of growth factors and COX-2 in the uterus during the preattachment and attachment reactions of the blastocyst with the luminal epithelium correlates with implantation failure in LIF-deficient mice.

Various mediators, including cytokines, growth factors, homeotic gene products, and prostaglandins (PGs), participate in the implantation process in an autocrine, paracrine, or juxtacrine manner. However, interactions among these factors that result in successful implantation are not clearly understood. Leukemia inhibitory factor (LIF), a pleiotropic cytokine, was shown to be expressed in uterine glands on day 4 morning before implantation and is critical to this process in mice. However, the mechanism by which LIF executes its effects in implantation remains unknown. Moreover, interactions of LIF with other implantation-specific molecules have not yet been defined. Using normal and delayed implantation models, we herein show that LIF is not only expressed in progesterone (P4)-primed uterine glands before implantation in response to nidatory estrogen, it is also induced in stromal cells surrounding the active blastocyst at the time of the attachment reaction. This suggests that LIF has biphasic effects: first in the preparation of the receptive uterus and subsequently in the attachment reaction. The mechanism by which LIF participates in these events was addressed using LIF-deficient mice. We observed that while uterine cell-specific proliferation, steroid hormone responsiveness, and expression patterns of several genes are normal, specific members of the EGF family of growth factors, such as amphiregulin (Ar), heparin-binding EGF-like growth factor (HB-EGF), and epiregulin, are not expressed in LIF(-/-) uteri before and during the anticipated time of implantation, although EGF receptor family members (erbBs) are expressed correctly. Furthermore, cyclooxygenase-2 (COX-2), an inducible rate-limiting enzyme for PG synthesis and essential for implantation, is aberrantly expressed in the uterus surrounding the blastocyst in LIF(-/-) mice. These results suggest that dysregulation of specific EGF-like growth factors and COX-2 in the uterus contributes, at least partially, to implantation failure in LIF(-/-) mice. Since estrogen is essential for uterine receptivity, LIF induction, and blastocyst activation, it is possible that the nidatory estrogen effects in the P4-primed uterus for implantation are mediated via LIF signaling. However, we observed that LIF can only partially resume implantation in P4-primed, delayed implanting mice in the absence of estrogen, suggesting LIF induction is one of many functions that are executed by estrogen for implantation.

Animals↗
PubMed2000

Direct competitive enzyme-linked immunosorbent assay for sulfamethazine.

A direct competitive enzyme-linked immunosorbent assay (ELISA) for screening sulfamethazine (SMZ) in pork tissues was developed. The assay was made with the affinity-purified polyclonal antibody-coated microtiter plate. A cross reactivity of IgG was observed at 3.5 microg/g of sulfamerazine among nine kinds of sulfonamide tested. Pork tissues fortified with SMZ was mixed with octadecyl silica (C18), and extracted with dichloromethane. The extracted SMZ was measured by homemade ELISA, commercial ELISA, and HPLC. The results were correlated (r=0.993, p<0.01). The homemade ELISA was sensitive to determine SMZ at the maximum residue level (MRL) as commercial one. During stability test of the IgG coated microtiter plate performed at 40 degrees C for 14 days, no difference in sensitivity was observed. We developed homemade ELISA with a detection limit of 10 ng of SMZ per g of pork tissues, and it could be used to screen SMZ in pork tissues.

Animals↗