Biomedical subjects

S S Han

Publications and source records attributed to S S Han.

At least 55 records · Page 3Linked to original sources

PubMed2000

Uterine artery Doppler velocimetry in the prediction of adverse obstetric outcomes in unexplained MSAFP elevations.

Unexplained maternal serum-fetoprotein (MSAFP) elevation has been known to be associated with adverse obstetric outcomes, however it is not sufficiently useful as a screening test. This study was undertaken to determine whether uterine artery Doppler velocimetry could define a subset of patients with an elevated MSAFP level in whom complications of pregnancy might develop. The subjects included 179 women between 26 and 28 weeks' gestation with MSAFP > or = 2.5 multiples of the median, in whom either the presence of an early diastolic notch or a resistance index 0.6 was considered as an abnormal Doppler velocimetry finding. Those subjects who displayed abnormal Doppler velocimetry findings showed an increased incidence of preeclampsia, preterm birth, IUGR, and IUFD compared to those subjects with only elevated MSAFP (p < 0.05). No differences were observed in the incidence of LBW. Positive predictive values of adverse obstetric outcomes were significantly higher in the group having both elevated MSAFP and abnormal Doppler velocimetry compared to the group with only elevated MSAFP (p < 0.05). Uterine artery Doppler velocimetry in the second trimester can improve the value of unexplained MSAFP elevation in the prediction of adverse obstetric outcomes.

Adult↗

PubMed1999

Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum.

In order to find antiviral substances from basidiomycetes, two water soluble substances, GLhw and GLlw, and eight methanol soluble substances, GLMe-1-8, were prepared from carpophores of Ganoderma lucidum. These substances were examined for their activities against five strains of pathogenic viruses such as herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), influenza A virus (Flu A) and vesicular stomatitis virus (VSV) Indiana and New Jersey strains in vitro. Antiviral activities were evaluated by the cytopathic effect (CPE) inhibition assay and plaque reduction assay. Five substances, GLhw, GLMe-1, -2, -4 and -7 significantly inhibited the cytopathic effects of HSV and VSV. In the plaque reduction assay, GLhw inhibited plaque formation of HSV-2 with 50% effective concentrations (EC50) of 590 and 580 microg/ml in Vero and HEp-2 cells, and its selectivity indices (SI) were 13.32 and 16.26. GLMe-4 did not exhibit cytotoxicity up to 1000 microg/ml, while it exhibited potent antiviral activity on the VSV New Jersey strain with an SI of more than 5.43. These results indicate the possibility of development of antiviral agents from basidiomycetous fungi.

Animals↗

PubMed1999

Antiherpetic activities of various protein bound polysaccharides isolated from Ganoderma lucidum.

To investigate antiherpetic substances from Ganoderma lucidum, various protein bound polysaccharides, GLhw, GLhw-01, GLhw-02, GLhw-03, were isolated by activity-guided isolation from water soluble substances of the carpophores. These substances were examined for their antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) by plaque reduction assay in vitro. Among them, the acidic protein bound polysaccharide, GLhw-02 of a brownish substance, exhibited the most potent antherpetic activity with 50% effective concentrations (EC50) of 300 approximately 520 microg/ml in Vero and HEp-2 cells, and its selectivity indices (SI) were more than 20. GLhw-02 was identified to consist mainly of polysaccharide (approximately 40.6%) and protein (approximately 7.80%) by anthrone test and Lowry-Folin test, and showed the usual molar ratio (C:H:O = 1:2:1) of carbohydrates by elemental analysis. These results suggest that GLhw-02 possesses the possibility of being developed from a new antiherpetic agent.

Acyclovir↗

PubMed1999

Effects of brazilin on GLUT4 recruitment in isolated rat epididymal adipocytes.

The effects of brazilin on glucose transport into isolated rat epididymal adipocytes were investigated. Brazilin increased [3H]2-deoxy-D-glucose uptake, which was characterized by an increase in Vmax with no effect on the Km value. Phenylarsine oxide, which inhibits the translocation of glucose transporters, decreased brazilin-stimulated glucose transport to the basal level. The inhibition of phosphatidylinositol 3-kinase (PI3-kinase) with wortmannin also blocked brazilin-stimulated glucose transport. Western blot analysis with an anti-GLUT4 antibody revealed that brazilin increased the translocation of GLUT4 from intracellular pools to the plasma membrane. Brazilin, in combination with phorbol ester, showed an additive effect on glucose transport. The stimulating effect of phorbol ester on glucose transport was inhibited by staurosporine, but the effect of brazilin remained unchanged. Protein kinase C activity was not influenced by brazilin treatment. The inhibition of protein synthesis showed no effect on brazilin-stimulated glucose transport, and GLUT4 content in the total membrane fraction was not altered as a result of treatment with brazilin for 4 hr. Metabolic labeling of GLUT4 with [35S]methionine showed that de novo synthesis of GLUT4 was not induced by brazilin. These data suggest that brazilin may increase glucose transport by recruitment of GLUT4 from intracellular pools to the plasma membrane of adipocytes via the activation of PI3-kinase. However, the effect of brazilin may not be mediated by GLUT4 synthesis and protein kinase C activation.

Adipocytes↗

PubMed1999

Role of -35 sequence and its cooperativity with vir-box for the expression of virE gene.

To elucidate the role of the -35 sequence and its cooperativity with vir box in the expression of the virE gene, various mutants were constructed by either site-directed mutation or deletional mutation of the virE promoter. The expression level of pHBAV, a mutant where its putative -35 sequences (CCGAGT) have been substituted with the consensus -35 sequences of the Escherichia coli promoter (TTGACA), was increased by 386%. pECHV, containing the conserved -35 sequence but lacking the vir box and the 5'-half of the imperfect dyad symmetry region (DSR) showed an increase of 286% in its promoter activity. pESHV, containing the conserved -35 sequence but lacking the complete 5'-upstream region from the mid-region of imperfect DSR, exhibited 244% of the native virE promoter activity. pHBCA, containing the conserved -35 sequence but destroying the vir box, was constructed by substitution of A, C, T at the positions -62, -63, and -65 on the vir-box to T, A, C, respectively. These mutations increased promoter activities by 319%. On the other hand, when the vir box was mutated from imperfect DSR to almost perfect DSR with T to A and G to T substitutions at -60 and -61 positions of the virE promoter containing the conserved -35 sequence (pHBNA), a higher activity of 671% was observed. These results demonstrate that when the putative -35 sequence of virE promoter is replaced with the consensus -35 sequence, the virE gene can be expressed independently without the binding of VirG protein to the vir-box and/or the induction of acetosyringone. Moreover, the presence of an almost perfect dyad symmetry of the vir-box can increase the expression of virE synergistically with the consensus -35 sequence.

Agrobacterium tumefaciens↗

PubMed1999

CpG oligodeoxynucleotides overcome the unresponsiveness of neonatal B cells to stimulation with the thymus-independent stimuli anti-IgM and TNP-Ficoll.

Neonates are very vulnerable to pathogenic encapsulated bacteria due to their inability to mount an antibody response to capsular polysaccharides, which are thymus-independent type 2 (TI-2) antigens (Ag). Oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides induced neonatal B cells to proliferate to anti-IgM, a TI-2 stimulus. CpG ODN inhibited the spontaneous and B cell receptor-mediated apoptosis of neonatal B cells and reduced the amount of the pro-apoptotic Bcl-xS, strongly correlated with anti-IgM-induced apoptosis of neonatal B cells. CpG ODN protected neonatal B cells from apoptosis by down-regulation of the Bcl-xS protein. Neonatal B cells underwent polyclonal differentiation upon stimulation with CpG ODN, but unlike in adult B cells, this was not preceded by IL-6 secretion. CpG ODN stimulated neonatal B cells to mount an Ag-specific antibody response to TNP-Ficoll, another TI-2 Ag. Thus CpG ODN could provide a novel approach to induce the immune system in neonates to respond to harmful encapsulated bacteria.

Animals↗

PubMed1999

Reversal of acute apparent diffusion coefficient abnormalities and delayed neuronal death following transient focal cerebral ischemia in rats.

Twenty-two rats were subjected to 8, 15, 30, or 60 minutes of temporary middle cerebral artery occlusion (n = 5 per group) or sham occlusion (n = 2) in the magnetic resonance imaging unit. Diffusion-, perfusion-, and T2-weighted imaging were acquired before and during occlusion, and after reperfusion. A coregistration method was used to correlate the acute changes of the average apparent diffusion coefficient (ADCav) with the histology after 72 hours at the same topographic sites. The initially reduced ADCav values recovered completely in both the lateral caudoputamen and upper frontoparietal cortex in the 8-, 15-, and 30-minute groups, partially in the cortex, and not at all in the caudoputamen in the 60-minute group. The histology showed that the caudoputamen was either normal or had mild neuronal injury in the 8-minute group and invariably had some degree of neuronal death in the 15-, 30-, and 60-minute groups, whereas the cortex was either normal or had varying degrees of neuronal injury in all groups. No histological abnormalities were seen in the sham-operated rats. Our data suggest that acute ADCav reversal does not always predict tissue recovery from ischemic injury and that temporary focal ischemia for even 8-minute duration can cause delayed neuronal death that is more severe in the caudoputamen where the initial ADCav decline was greater than in the cortex.

Animals↗

PubMed1999

Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappa B, and p53.

It has been well known that curcumin is a powerful inhibitor of proliferation of several tumor cells. However, the molecular basis of the anti-proliferative effect of curcumin has not been investigated in detail. In this paper, we present evidence to show that curcumin inhibited proliferation of a variety of B lymphoma cells. At low concentrations curcumin inhibited the proliferation of BKS-2, an immature B cell lymphoma, more effectively than that of normal B lymphocytes and caused the apoptosis of BKS-2 cells in a dose- and time-dependent manner. Furthermore, curcumin downregulated the expression of survival genes egr-1, c-myc, and bcl-X(L) as well as the tumor suppressor gene p53 in B cells. In addition, NF-kappaB binding activity was also downregulated almost completely by curcumin. Stimulation with CpG oligonucleotides or anti-CD40 overcame growth inhibition induced by low concentrations of curcumin. Our results suggest that curcumin caused the growth arrest and apoptosis of BKS-2 immature B cell lymphoma by downregulation of growth and survival promoting genes.

Animals↗

PubMed1999

Prevention of ultraviolet radiation-induced suppression of contact hypersensitivity by Aloe vera gel components.

We have recently reported that Aloe vera gel contains small molecular weight immunomodulators, G1C2F1, that restore ultraviolet B (UVB)-suppressed accessory cell function of epidermal Langerhans cells (LC) in vitro. In the present study we evaluated the UVB-protective activity of G1C2F1 in vivo. Exposure of the shaved abdominal skin of mice to 2.4 KJ/m2 of UVB radiation resulted in suppression of contact sensitization through the skin to 41.1%, compared to normal unirradiated skin. Topical application of G1C2F1 immediately after irradiation reduced this suppression significantly. The percentage recovery of UVB-suppressed contact hypersensitivity (CHS) response was 52.3, 77.3, and 86.6% when the irradiated skin was treated once with 0.1, 0.5, and 2.5 mg/ml of G1C2F1-containing cream, respectively. G1C2F1 did not show nonspecific stimulatory activity on CHS response. The present study, together with the previous observation, show that Aloe vera gel contains small molecular weight immunomodulators that prevent UVB-induced immune suppression in the skin by restoration of UVB-induced damages on epidermal LC.

Adjuvants, Immunologic↗

PubMed1999

CpG oligodeoxynucleotides rescue BKS-2 immature B cell lymphoma from anti-IgM-mediated growth inhibition by up-regulation of egr-1.

Cross-linking of the IgM antigen receptor on an immature B cell lymphoma (BKS-2) induces growth arrest and apoptosis. This is accompanied by down-regulation of the immediate early genes, egr-1 and c-myc, and a reduction in NF-kappaB activity. Anti-IgM-induced growth arrest and apoptosis of this murine B cell lymphoma were prevented by oligodeoxynucleotides (ODN) containing the CpG motif, which are also known to be stimulatory for mature and immature B cells. The CpG but not non-CpG ODN rescued BKS-2 cells from anti-IgM-mediated growth inhibition by up-regulation of egr-1 and c-myc expression as well as by restoring NF-kappaB activity. Interestingly, changes in egr-1 expression occurred more rapidly than in c-myc expression. Also the c-myc levels remained high up to 6 h after addition of the anti-IgM, which was also the time until which the addition of CpG could be delayed without affecting its ability to provide complete protection. This CpG-induced rescue of B lymphoma cells was blocked by antisense egr-1 ODN, suggesting that the expression of egr-1 is important for the effects of CpG ODN on the growth and survival of BKS-2 cells.

Animals↗

PubMed1999

Hepatic involvement in hypereosinophilia: sonographic findings.

Hypereosinophilic syndrome may cause eosinophil-related tissue damage to various organs. The purpose of this paper is to describe sonographic findings in 13 patients with hypereosinophilia in whom the liver was involved. The diagnosis in these 13 patients was based on liver biopsy in seven patients with bone marrow biopsy in six patients. Eight patients had hypereosinophilic syndrome and five patients had clonorchiasis. All 13 patients had mild to marked hepatomegaly. Seven of 13 patients showed multiple round or oval hypoechoic (n = 6) or variably echogenic (n = 1) lesions measuring 1 to 2 cm with poorly defined margins in both lobes of the liver. Four patients had one or two hypoechoic lesions 3 to 4 cm in size, with geographic pattern and poorly defined margins. Two patients showed diffuse hepatomegaly with increased parenchymal echogenicity. The number of lesions and the extent of diffuse lesions seem to be proportional to the degree of eosinophilia. Hypereosinophilia may produce multiple small focal hepatic lesions or diffuse segmental or lobar echogenic lesions simulating primary or metastatic tumor of the liver.

Adult↗

PubMed1999

Effect of p53 tumor suppressor on nucleotide excision repair in human colon carcinoma cells treated with 4-nitroquinoline 1-oxide.

In probing the mechanism of nucleotide excision repair (NER) in response to 4-nitroquinoline 1-oxide (4NQO)-induced DNA damage, the effect of p53 tumor suppressor was investigated. The effect of p53 protein on the repair of damaged DNA was examined by comet assay. Expression of p53 and p21(Waf1/Cip1) proteins was measured by the Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry, respectively. Compared to RKO cells having the wild-type p53 gene, increased cytotoxicity by 4NQO was observed in RKOmp53 cells with a mutation in p53 protein. DNA single strand breaks (SSB), indicative of the DNA repair, were considerably increased in 4NQO-treated RKO cells. Also, the expression of p53 and p21 proteins was significantly increased in 4NQO-treated RKO cells. In RKOmp53 cells, no effect of 4NQO on p21 expression was observed. Our findings suggest that 4NQO-induced NER is p53-dependent and involves up-regulation of its downstream regulator, p21(Waf1/Cip1) proteins.

4-Nitroquinoline-1-oxide↗

PubMed1999

Mild hyperthermia-induced apoptosis is dependent on p53 in human lymphoid cells.

Mild hyperthermia is known to enhance apoptosis. The p53 tumor-suppressor gene product has been shown to function in apoptosis in response to genotoxic stress. However, there is little information regarding the mechanism of p53-dependent apoptosis induced by heat stress. In present study, a p53 contribution in mild hyperthermia-induced apoptosis was investigated in human lymphoid system. After 30-minute exposure at 44 degrees C, the accumulation of p53 protein was clearly observed in TK6 and ML-1 cells. Using comet assay, the more significant sensitivity to hyperthermic apoptosis was found in TK6 (wild-type p53) than in WI-L2-NS (mutated in p53). Furthermore, the significantly rapid shifting from early apoptotic phase to late apoptotic was observed in heat-induced p53 TK6 cells. These findings suggest that p53-dependent apoptosis is efficaciously induced by mild hyperthermia as non-genotoxic stress in human lymphoid system.

Apoptosis↗

PubMed1998

Simultaneous determination of flupyrazofos and its metabolite 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole and flupyrazofos oxon in rat plasma by high-performance liquid chromatography with ultraviolet absorbance detection.

An isocratic high-performance liquid chromatography (HPLC) system with UV detection was developed for simultaneous determination of flupyrazofos and its metabolites, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole and flupyrazofos oxon, in rat plasma. Optimal analytical conditions involved an analytical cartridge column consisting of a phenyl bonded phase, a mobile phase of 50 mM phosphate buffer (pH3.0)-acetonitrile (40:60, v/v) and a UV detection wavelength of 232 nm. Under these conditions the peaks of flupyrazofos and its metabolites were all well separated and the total time for complete separation was less than 12 min. The limit of quantitation was 40 ng/ml for flupyrazofos and 20 ng/ml for PTMHP. Recoveries from rat plasma were higher than 90%. Following intravenous administration of flupyrazofos, the method has been successfully applied in a toxicokinetic study in rats involving plasma samples. Therefore, the current method is a valuable analytical tool for investigating the metabolism and toxicokinetics of flupyrazofos.

Animals↗

PubMed1998

Effects of beta-ionone on the expression of cytochrome P450s and NADPH-cytochrome P450 reductase in Sprague Dawley rats.

We have recently reported that beta-ionone induces cytochrome P450 (P450) 2B1 in rats. Effects of beta-ionone on the expression of other P450 isozymes and NADPH-P450 reductase were further investigated in Sprague Dawley rats. Administration of beta-ionone subcutaneously 72 and 48 h before sacrificing the animals not only significantly induced the liver microsomal activities of P450-associated enzymes and NADPH-P450 reductase, but also clearly increased in the level of P450 1A1/2, P450 2C, and NADPH-P450 reductase proteins. The induction of P450 1A1/2 and 2C by beta-ionone was much greater in male than in female as measured by western immunoblotting. Reverse transcriptase-polymerase chain reactions showed that, in addition to P450 2B1 and 2B2 mRNAs, P450 1A2, 2C6 and NADPH-P450 reductase mRNAs were increased when beta-ionone was administered. Our previous and present results indicated that beta-ionone may induce several P450s and NADPH-P450 reductase by the accumulation of their corresponding mRNAs.

Animals↗

PubMed1998

Pharmacokinetic analysis for assessing developmental toxicity of a new synthetic acetolactate synthase inhibitor, LGC-40863, in rats.

Effects of O-[2,6-bis[(4,6-dimethoxy-2pyrimidinyl)oxy]benzoyl]oxime (LGC-40863) on dams and embryonic development were examined at p.o. doses of 500, 1000 and 2000 mg/kg/day on days 6 to 15 of gestation in rats. No significant maternal or embryonic toxicity was observed at any of the doses. However, external fetal anomalies including brachycephaly, microcephaly, micrognathia, agnathia, lordosis and edema were observed at an incidence of 2.2% at the lowest dosage level but not at higher dosages. Because these malformations are not common as spontaneous variations in rats, we carried out a toxicokinetic study to clarify whether the fetal anomalies at 500 mg/kg are related to LGC-40863. During multiple p.o. administrations of LGC-40863 at the same doses used in the developmental toxicity study, LGC-40863 was not detected in the systemic circulation. Moreover, 3 months of multiple dosing did not alter its plasma level. In the pregnant rats receiving 500 mg/kg on 10 consecutive days of gestation, LGC-40863 was also undetectable. However, after i.v. administration, high levels of the drug were found in plasma, and these could be described by a two-compartment model. These results demonstrate that the bioavailability of LGC-40863 is negligible. To investigate a possible relevance of metabolite(s) to the fetal anomalies, we examined excretion of radioactivity after p.o. doses of 500 and 2000 mg/kg of LGC-40863 spiked with [14C]LGC-40863. For both doses, cumulative recovery up to 72 hr was approximately 80% and 9% in feces and urine, respectively, indicating dose linearity in the elimination kinetics. Overall, these toxicokinetic data suggest that the fetal anomalies observed at 500 mg/kg are not associated with LGC-40863 but are spontaneously generated. In conclusion, LGC-40863 had neither significant maternal nor developmental toxicity at any of the doses tested for p.o. exposure.

Abnormalities, Drug-Induced↗

PubMed1997

Role of Egr-1 gene expression in B cell receptor-induced apoptosis in an immature B cell lymphoma.

Ligation of B cell receptor (BCR) on BKS-2, an immature B cell lymphoma by anti-IgM antibodies (Ab) caused apoptosis. Here we report that signaling through B cell receptor in wild type BKS-2 cells down-regulated the expression of Egr-1, a zinc finger-containing transcription factor. A reduction in the level of Egr-1 mRNA could be demonstrated as early as 30 min after the ligation of BCR on BKS-2 cells. Immunocytochemical and Western blot analysis revealed that the expression of EGR-1 protein was also inhibited by anti-IgM treatment. Antisense oligonucleotides to Egr-1 caused growth inhibition and apoptosis in BKS-2 cells, suggesting that expression of Egr-1 is important for the survival of these B lymphoma cells. In contrast to wild type BKS-2 cells, the mutant 1. B5 cell line, which is refractory to B cell receptor-mediated growth-inhibitory signals, showed an increased expression of Egr-1 upon treatment with anti-IgM. These results implicate a role for Egr-1 in blocking B cell receptor-mediated apoptosis in immature B cells.

Animals↗

PubMed1997

Early growth response-1-dependent apoptosis is mediated by p53.

The early growth response-1 (EGR-1) protein is an anti-proliferative signal for certain tumor cells and is required for apoptosis induced by stimuli that elevate intracellular Ca2+. We present evidence that EGR-1 transactivates the promoter of the p53 gene and up-regulates p53 RNA and protein levels. Inhibition of p53 function with dominant-negative p53 mutants abrogates EGR-1-dependent apoptosis. These findings establish a direct functional link between EGR-1 and the p53-mediated cell death pathway and suggest that mutant forms of p53 in tumor cells may provide resistance to the anti-proliferative effects of EGR-1.

Apoptosis↗