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Biomedical subjects

J S Yang

Publications and source records attributed to J S Yang.

At least 73 records · Page 4Linked to original sources

Xanthones from Hypericum japonicum and H. henryi.

From the aerial part of Hypericum japonicum, one new xanthone glycoside, 1,5-dihydroxyxanthone-6-O-beta-D-glucoside, one novel dimer xanthone, bijaponicaxanthone, and the first natural prenylated xanthone, 1,3,5,6-tetrahydroxy-4-prenylxanthone, were isolated together with the four known xanthones, 1,5,6-trihydroxyxanthone, isojacereubin, 6-deoxyisojacareubin and 4',5'-dihydro-1,5,6-trihydroxy-4',4',5'-trimethylfurano (2',3':4,5) xanthone. five previously known xanthones, kielcorin, cadensin, 1,7,-dihydroxyxanthone, 1,5-dihydroxy-4-methoxyxanthone and 1,2,5-trihydroxyxanthone were also found in the dichoromethane extract of the stems and leaves of H. henryi. Their structures were elucidated by spectroscopic and chemical methods. Some of the compounds from H. japonicum were found to exert an interesting coagulant activity in an in vitro test. The chemotaxonomic value of xanthones is discussed briefly.

Animals↗

Comparison of human liver and small intestinal glutathione S-transferase-catalyzed busulfan conjugation in vitro.

The apparent oral clearance of busulfan has been observed to vary as much as 10-fold in the population of children and adults receiving high-dose busulfan. The only identified elimination pathway for busulfan involves glutathione conjugation. The reaction is predominantly catalyzed by glutathione S-transferase (GST) A1-1, which is present in both liver and intestine. The purpose of this study was to compare busulfan Vmax/Km in cytosol prepared from adult human liver and small intestine. Tetrahydrothiophenium ion formation rate per milligram of cytosolic protein was constant along the length (assessed in 30-cm segments) of three individual small intestines. A 30-cm-long intestinal segment 90-180 cm from the pylorus was chosen to be representative of intestinal cytosolic busulfan conjugating activity. Busulfan Vmax/Km (mean +/- SD) in cytosol prepared from 23 livers and 12 small intestines was 0.166 +/- 0.066 and 0.176 +/- 0.085 microl/min/mg cytosolic protein, respectively, in incubations with 5 microM busulfan, 1 mM glutathione, and 2 mg of cytosolic protein. The relative content of GSTalpha (A1-1, A1-2, and A2-2) was compared for human liver and intestinal cytosol using Western blot. The levels of GSTalpha in liver and intestinal cytosol were 1.12 +/- 0.56 and 1.36 +/- 0.32 integrated optimal density units/5 microg cytosolic protein, respectively. Busulfan conjugation in vitro was comparable per milligram of cytosolic protein in liver and intestinal cytosol.

Busulfan↗

Lentiviral vectors for gene therapy of cystic fibrosis.

A replication-defective vector based on human immunodeficiency virus (HIV) was evaluated for gene transfer directed to the lung. The tropism of this vector has been expanded through the incorporation of the vesticular stomatitis virus G protein into its envelope. The HIV vector effectively transduced nondividing airway epithelial cells in vitro whereas a murine-based retroviral vector did not. Experiments in a human bronchial xenograft model demonstrated high-level gene transduction with a cystic fibrosis transmembrane conductance regulator (CFTR) HIV vector into undifferentiated, cystic fibrosis (CF)-derived cells of the xenograft. CFTR expression was stable and capable of functional correction of the CF defect after the graft matured. The HIV vector did not effectively transduce cells of the xenograft when instilled after the epithelium had differentiated. This block to transduction appears to be at the level of entry, although post entry restrictions cannot be ruled out. Further development of this vector system for CF gene therapy should focus on a better understanding of potential entry and post entry blocks.

Animals↗

Oxidation of cyclophosphamide to 4-hydroxycyclophosphamide and deschloroethylcyclophosphamide in human liver microsomes.

We have investigated the formation of 4-hydroxycyclophosphamide (HCY) and deschloroethylcyclophosphamide (DCCY) from cyclophosphamide (CY) in human liver microsomes. For HCY, the estimated values (mean +/- SD; n = 3) of Km1 and Km2 were 0.095 +/- 0.072 and 5.09 +/- 4.30 mM, and the estimated values of Vmax1 and Vmax2 were 0.138 +/- 0.070 and 1.55 +/- 0.50 nmol/min/mg protein. For DCCY, Km1 and Km2 were 0.046 +/- 0.017 and 8.58 +/- 5.84 mM, and Vmax1 and Vmax2 were 0.006 +/- 0.003 and 0.274 +/- 0.214 nmol/min/mg protein. At CY concentrations of 0.1, 0.7, and 5 mM, HCY respectively accounted for 95.7 +/- 1.3, 95.1 +/- 2.4, and 90.7 +/- 2.7% of the total products of CY (HCY + DCCY; n = 6). In a separate experiment, 98.7 +/- 11.9% (n = 3) of CY loss could be accounted for by the formation of HCY at 0.1 mM CY. On the basis of cytochrome P450 (CYP) isoform-specific chemical inhibitor and cDNA-expressed human P450 isozyme studies, CYP2C9 and CYP3A4/5 seemed to be the major P450 isoforms responsible for HCY formation at low (0.1 mM) and high (0.7 and 5 mM) concentrations of CY, respectively. Although orphenadrine inhibition was observed in human liver microsomes (which has been taken to indicate CYP2B6 catalysis), orphenadrine inhibited cDNA-expressed CYP3A4 formation of HCY to the same extent observed in human liver microsomes, and the addition of orphenadrine to incubations containing sulfaphenazole (a specific inhibitor of CYP2C9) or troleandomycin (a specific CYP3A inhibitor) did not increase inhibition beyond that observed with sulfaphenazole or troleandomycin alone. Similar studies indicated that CYP3A4/5 was the major P450 isoform responsible for DCCY formation at high (0.7 and 5 mM) concentrations of CY. The P450 isoform responsible for DCCY formation at 0.1 mM CY could not be identified due to its very low formation rate.

Aryl Hydrocarbon Hydroxylases↗

Korean analytical quality assurance (KAQUA) program for biological monitoring.

The Korean analytical quality assurance (KAQUA) program on biological monitoring was performed by the Industrial Health Research Institute in Korea in spring, 1995. The object of the KAQUA program is to improve the analysis capability for the biological monitoring of hazardous chemicals and to confirm the reliability of data from each laboratory. The items chosen for the first round were analyses of lead in blood (PbB) and of hippuric acid in urine (HAU). Eighty-eight laboratories in Korea participated in this program. Two levels of samples, randomly chosen among six levels for each item, were sent to the participants. The consensus value from participants and reference laboratories was determined by statistical analysis and used as a reference value. The tolerance range was +/-15% (+/-6 micrograms/dl for PbB below 40 micrograms/dl) of the reference value. The mean proficiency rate of analytical data increased dramatically in the first round compared with a pre-round that was provided as part of a training course for participants before performing the first round. The mean proficiency rate of PbB was 69% at pre-round and increased at 91% at the first round; for HAU the increase was from 58% to 88%. Not only the analytical results but also raw data were reviewed to find problems which might have arisen during the analytical process. Re-education courses provided after final evaluation of each participant by means of telephone discussion, correspondence course, and experimental practice, were helpful in achieving the purpose of the analytical quality assurance program.

Chemistry, Clinical↗

Purification and characterization of an SDS-activated fibrinolytic enzyme from Eisenia fetida.

A sodium-dodecyl-sulfate-activated fibrinolytic enzyme from Eisenia fetida (the E. fetida enzyme) was purified by chromatography on DEAE Sepharose, Sephadex G-75, and Phenyl Sepharose 4. It (M(r) = 45 kDa) was composed of two subunits (M(r) = 26 kDa and M(r) = 18 kDa) held together by hydrophobic interactions. The enzyme displayed four activities when we used fibrin plates to detect the proteolytic activity. These were designated as CFPg (complete fibrinolysis in the plasminogen-rich plate), uCFPg (uncompleted fibrinolysis in the plasminogen-rich plate), CF (complete fibrinolysis in the plasminogen-free plate), and uCF (uncompleted fibrinolysis in the plasminogen-free plate). SDS activated CFPg and rendered the enzyme more sensitive to some inhibitors. Leupeptin, chymostatin, pepstatin, aprotinin, phenylmethylsulfonyl fluoride, and dithiothreitol had no effect on uCF. Pepstatin stimulated CFPg and uCFPg, while E-64, a thiol inhibitor, activated uCFPg and uCF. The N-terminal sequence of the large subunit was analyzed and compared with some known proteins. The large subunit alone had catalytic activity, while the small subunit did not. Using plasminogen as the substrate for defining peptide bond specificity, the E. fetida enzyme was observed to cleave the carboxyl side of basic amino acids, small neutral amino acids, and Met residue.

Amino Acid Sequence↗

[Isoflavones from Glycyrrhiza eurycarpa].

A new isoflavone, named eurycarpin A and a new natural product isoflavone named eurycarpin B have been isolated from the roots of Glycyrrhiza eurycarpa P. C. Li. Their structures were determined to be 7,2',4'-trihydroxy-3'-(3,3-dimethylallyl) isoflavone(I) and 7,2'-dihydroxy-6",6"-dimethylpyrano-(2",3":4',3') isoflavone(II) on the basis of spectroscopic analysis (UV, EI-MS, 1HNMR, 13CNMR, NOE difference and HMBC). In addition, three known isoflavones, licoisoflavone A, calycosin and formononetin, were obtained for the first time from this plant.

Drugs, Chinese Herbal↗

[Studies on the ganoderic acid, a new constituents from the fruiting body of Ganoderma lucidum (Fr.) Karst].

Three compounds have been isolated from the dichloromethane soluble fraction of the fruiting body of Ganoderma lucidum (Fr.) Karst. On basis of spectral analyses (UV, IR, MS, 1HNMR, 13CNMR and 2D-NMR), they were identified as 3, 7-dioxo-lanosta-8, 24(E)-dien-26-oic acid (I), 7 beta-15 alpha-dihydroxy-3, 11, 23-trioxo-5 alpha-lanost-8-en-26-oic acid (II) and 3 beta, 7 beta, 15 alpha-trihydroxy-11, 23-dioxo-5 alpha-lanosta-8-en-26-oic acid (III). Compound I is a new compound named ganoderic acid DM.

Drugs, Chinese Herbal↗

Lead concentrations in blood among the general population of Korea.

The purpose of this survey was to obtain information on the overall blood lead concentrations of the Korean population due to environmental exposure. Five hundred and twenty-five Korean adults from four provinces who had no previous occupational exposure to lead were chosen by random sampling to represent the general (normal) population. Blood lead determinations were performed by atomic absorption spectrometry with a graphite furnace. Interlaboratory quality control for analysis of blood lead was carried out in seven laboratories in Korea and Europe. The geometric mean were 6.36 micrograms/dl for males and 5.09 micrograms/dl for females. There was no correlation between blood lead concentration and age. The mean concentration of blood lead in smokers was higher than that in nonsmokers (P < 0.0005). The mean blood lead concentration in male nonsmokers was higher than that in female nonsmokers (P < 0.0005). Differences in mean blood lead values according to residential area were observed, and this result showed good agreement with the results of ambient monitoring.

Adult↗

Survey of natural occurrence of trichothecene mycotoxins and zearalenone in Korean cereals harvested in 1992 using gas chromatography/mass spectrometry.

For the survey of the natural occurrence of trichothecene mycotoxins, produced by species of fungi imperfecti such as Fusarium and Trichothecium, a sensitive analytical method was developed for the simultaneous detection and quantitation of the major trichothecene mycotoxins, viz. T-2 toxin (T-2), HT-2 toxin (HT-2), nivalenol (NIV), fusarenon-X (F-X), deoxynivalenol (DON), 3-acetyl deoxynivalenol (3-Ac DON), and zearalenone (ZEN), using gas chromatography/mass spectrometry-selected ion monitoring (GC/MS-SIM) mode after trimethyl silyl derivatization. The incidence of NIV and DON in 30 barley samples were 93% and 67%, respectively; the average contents of NIV and DON in positive samples were 390 ng/g (range 40-2038) and 106 ng/g (range 5-361) respectively. In 15 maize samples, the incidences of NIV and DON were 53% and 93% respectively and the average contents were 168 ng/g and 145 ng/g, respectively. These results suggest that NIV and DON were the major contaminating trichothecene mycotoxins in Korean barley and maize samples harvested in 1992.

Edible Grain↗

Molecularly cloned feline immunodeficiency virus NCSU1 JSY3 induces immunodeficiency in specific-pathogen-free cats.

A full-length feline immunodeficiency virus NCSU1 (FIV-NCSU1) genome (JSY3) was cloned directly from FIV-NCSU1-infected feline CD4+ lymphocyte (FCD4E) genomic DNA and identified by PCR amplification with 5' long terminal repeat, gag, env, and 3' long terminal repeat primer sets. Supernatant from FCD4E cells cocultured with JSY3-transfected Crandell feline kidney (CrFK) cells was used as an inoculum. Cell-free JSY3 virus was cytopathogenic for FCD4E lymphocytes but did not infect CrFK cells in vitro. To determine in vivo infectivity and pathogenesis, six young adult specific-pathogen-free cats were inoculated with cell-free JSY3 virus. Provirus was detected at 2 weeks postinfection (p.i.) and was still detectable at 25 weeks p.i. as determined by gag region PCR-Southern blot analysis of peripheral blood mononuclear cell lysates. Infectious virus was recovered from peripheral blood mononuclear cells at 6 and 25 weeks p.i., and an antibody response to FIV was detected by 4 weeks. In the acute phase of infection, JSY3 provirus was found only in the CD4+ lymphocyte subset; however, by 14 weeks p.i., the greatest provirus burden was detected in B lymphocytes. All six cats were panlymphopenic at 2 weeks p.i., CD4+/CD8+ ratios were inverted by 6 weeks p.i., and five of the six cats developed lymphadenopathy by 10 weeks p.i. To determine if the JSY3 molecular clone caused immunodeficiency similar to that of the parental wild-type FIV-NCSU1, the cats were challenged with the low-virulence ME49 strain of Toxoplasma gondii at 29 weeks p.i. Five of six cats developed clinical signs consistent with generalized toxoplasmosis, and three of six cats developed acute respiratory distress and required euthanasia. Histopathologic examination of the severely affected cats revealed generalized inflammatory reactions and the presence of T. gondii tachyzoites in multiple tissues. None of the six age- and sex-matched specific-pathogen-free cats inoculated with only T. gondii developed clinical disease. Our results suggest that the pathogenesis of the molecularly cloned NCSU1 JSY3 is similar to that of wild-type FIV-NCSU1.

Animals↗

[New ellagic glycosides and known triterpenoids from Duchesnea indica Focke].

Two new ellagic glycosides, named ducheside A and ducheside B, have been isolated from Ducheside indica Focke. Their structures were established as 3'-O-methyl-ellagic acid-4-O-beta-D-xylopyranoside (I), 3'-O-methyl-ellagic acid-4-O-alpha-L-arabinofuranoside (II), respectively, on the basis of chemical method and spectral analysis. In addition, four known compounds were isolated and identified as 3 beta-hydroxylurs-12-en-28-oic acid (III), 2 alpha, 3 beta, 19 alpha-trihydroxylurs-12-en-28-oic acid (IV), 2 alpha, 3 beta, 19 alpha-trihydroxylurs-12-en-28-oic acid 28-O-beta-D-glucopyranoside (V), 2 alpha, 3 alpha, 19 alpha-trihydroxylurs-12-en-28-oic acid 28-O-beta-D-glucopyranoside (VI). Compounds IV, V, VI were isolated for the first time from Duchesnea genus.

Molecular Structure↗

Seizures associated with stroke in childhood.

Seventy-three consecutive children younger than 17 years of age seen from 1978 to 1992 with acute hemiplegia from stroke, were retrospectively reviewed to evaluate the incidence of seizures and the risks of recurrent seizures after stroke. The population consisted of 56 children with cerebral infarction, 12 with intracranial hemorrhage, and 5 with transient ischemic attack. Children whose strokes occurred in the neonatal period and those secondary to trauma, malignancy, or infection were excluded. Mean follow-up time was 43.5 months (range: 12-156 months). At least 1 seizure occurred in 36 patients (49.3%) and recurrent seizures occurred in 21 patients (28.8%). Recurrent seizures developed more often among patients who had initial seizures with delayed onset (P < .05). In 56 patients with cerebral infarction, 16 of 31 patients (51.6%) with cortical involvement documented by neuroradiologic studies and 1 of 25 patients (4%) without cortical involvement developed recurrent seizures (P < .01). In 12 patients with intracranial hemorrhage, 3 of 10 patients with cortical involvement and none of 2 patients without cortical involvement developed recurrent seizures. It is concluded that seizures commonly occur in childhood stroke. Risk factors for recurrent seizures include later onset of initial seizures and presence of cortical involvement.

Adolescent↗

Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease.

AIM: To evaluate the efficacy and safety of tablet huperzine-A (Hup) in patients with Alzheimer's disease. METHODS: Using multicenter, prospective, double-blind, parallel, placebo controlled and randomized method, 50 patients were administered orally 0.2 mg (4 tablets) Hup and 53 patients were given po 4 tablets of placebo bid for 8 wk. All patients were evaluated with Wechsler memory scale, Hasegawa dementia scale, mini-mental state examination scale, activity of daily living scale, treatment emergency symptom scale, and measured with BP, HR, ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine. RESULTS: About 58% (29/50) of patients treated with Hup showed improvements in their memory (P < 0.01), cognitive (P < 0.01), and behavioral (P < 0.01 functions. The efficacy of Hup was better than placebo (36%, 19/53) (P < 0.05). No severe side effect was found. CONCLUSION: Hup is a promising drug for symptomatic treatment of Alzheimer's disease.

Aged↗