Biomedical subjects

S Cho

Publications and source records attributed to S Cho.

At least 91 records · Page 5Linked to original sources

PubMed2000

The association between glutathione S-transferase M1 genotype and polycyclic aromatic hydrocarbon-DNA adducts in breast tissue.

A major goal in molecular epidemiology is to identify preventable environmental risk factors and susceptible subpopulations. In a hospital-based molecular epidemiological case-control study of breast cancer, we investigated the relationship between DNA damage from exposure to polycyclic aromatic hydrocarbons (PAHs) and susceptibility attributable to inherited deletion of the xenobiotic detoxifying gene, glutathione S-transferase M1 (GSTM1). Prior to breast surgery, women (n = 227) were enrolled and interviewed and donated a blood sample. PAH-DNA adduct levels were measured by immunohistochemistry in breast tissue samples retrieved from pathology blocks, and GSTM1 genotype was determined by PCR using WBC DNA. The GSTM1 analysis included 95 cases and 87 benign breast disease controls. GSTM1 genotype was not associated with breast cancer case-control status (odds ratio = 0.73; 95% confidence interval, 0.37-1.44). However, the GSTM1 null genotype predicted PAH-DNA adduct levels in malignant (beta = 0.407; P = 0.003) and nonmalignant (beta = 0.243; P = 0.05) breast tissue from cases. This relationship was not seen in tissue from controls (beta = 0.095; P = 0.341). When tissue from controls was compared with tumor tissue from cases, there was a significant case-control difference in PAH-DNA adduct levels among women who were GSTM1 null. There was no such case-control difference among women who were homozygous or heterozygous for GSTM1. There was an interaction between GSTM1 and case-control status on adduct levels in breast tissue (P = 0.002). The results suggest that genetic susceptibility to the formation of PAH-DNA adducts in breast tissue may play a role in breast cancer development.

Adult↗

PubMed1999

Open tubular capillary electrochromatography in etched, chemically modified 20 microns I.D. capillaries.

Fused silica capillaries with an I.D. of 20 microns are etched and then chemically modified by the silanization/hydrosilation method to attach an octadecyl moiety for use in electrokinetic chromatography. The etched capillaries after chemical modification are shown to have an anodic electroosmotic flow below pH 4.5. In comparison to bare 20 microns capillaries and unetched but chemically modified 20 microns capillaries, the etched C18 fused silica tubes show better separation of mixtures of lysozymes and cytochrome c's under identical conditions of buffer, pH and applied voltage. It was also demonstrated that this open tubular approach to capillary electrochromatography was amenable to a number of different types of basic compounds ranging in size from typical small amines to biomolecules. As expected, pH is an important variable that must be controlled in order to obtain an optimized separation. Reproducibility studies verify the stability of the silicon-carbon linkage produced in this modification method so that column lifetimes of at least 300 injections can be expected.

Capillary Action↗

PubMed1999

Tyrosine hydroxylase, aromatic L-amino acid decarboxylase and dopamine metabolism after chronic treatment with dopaminergic drugs.

Mice were treated with dopamine (DA) receptor agonist and antagonist drugs: Agonists: (+/-)-SKF 38393 ((+/-)-1-phenyl-2,3,4, 5-tetrahydro-(1H)-3-benzazepine-7,8-diol) [DA D1-like]; bromocriptine, [DA D2 selective]; quinpirole, [DA D2/D3 preferring]; (+/-)-7-hydroxy-dipropylamino-tetralin (7-OH-DPAT), [DA D3/D2 preferring], Antagonists: R(+)-SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine), [DA D1-like]; and haloperidol, [DA D2-like]. All drugs were administered intraperitoneally, two injections daily 8 h apart for 30 days. Aromatic L-amino acid decarboxylase (AAAD) and tyrosine hydroxylase (TH) activity, protein and mRNA, as well as DA metabolism were followed with time thereafter in the nigrostriatal neurons. We observed that chronic administration of D1-like agonists had no effect on TH or AAAD activity, while D2-like agonists decreased AAAD, but not TH activity. Additionally, chronic blockade of DA D2-like receptors resulted in prolonged induction of TH and AAAD, while chronic blockade of DA D1-like receptors induced changes of AAAD only. Compared to TH the induction of AAAD was longer lasting. DA metabolism was altered by chronic administration of drugs acting on DA D2-like, but not DA D1-like receptors, and in general the patterns of change did not follow those for TH or AAAD. When studied 48 h after the last dose of the chronic haloperidol schedule TH displayed tolerance to acute drug challenge. At the same time interval, there was tolerance to the enhancing effects of haloperidol and SCH 23390 on DA metabolism. The induction of AAAD by haloperidol or SCH 23990 did not appear to develop tolerance after chronic administration. These observations complement existing knowledge, and provide novel information about AAAD that may have practical importance for Parkinson's patients on L-DOPA therapy.

Animals↗

PubMed1999

Blockade of tetrahydrobiopterin synthesis protects neurons after transient forebrain ischemia in rat: a novel role for the cofactor.

The generation of nitric oxide (NO) aggravates neuronal injury. (6R)-5,6,7,8-Tetrahydro-L-biopterin (BH4) is an essential cofactor in the synthesis of NO by nitric oxide synthase (NOS). We attempted to attenuate neuron degeneration by blocking the synthesis of the cofactor BH4 using N-acetyl-3-O-methyldopamine (NAMDA). In vitro data demonstrate that NAMDA inhibited GTP cyclohydrolase I, the rate-limiting enzyme for BH4 biosynthesis, and reduced nitrite accumulation, an oxidative metabolite of NO, without directly inhibiting NOS activity. Animals exposed to transient forebrain ischemia and treated with NAMDA demonstrated marked reductions in ischemia-induced BH4 levels, NADPH-diaphorase activity, and caspase-3 gene expression in the CA1 hippocampus. Moreover, delayed neuronal injury in the CA1 hippocampal region was significantly attenuated by NAMDA. For the first time, these data demonstrate that a cofactor, BH4, plays a significant role in the generation of ischemic neuronal death, and that blockade of BH4 biosynthesis may provide novel strategies for neuroprotection.

Animals↗

PubMed1999

Neuroprotection and neuronal differentiation studies using substantia nigra dopaminergic cells derived from transgenic mouse embryos.

The major pathological lesion of Parkinson's disease (PD) is the selective cell death of dopaminergic (DA) neurons in substantia nigra (SN). Although the initial cause and subsequent molecular signaling mechanisms leading to DA cell death underlying the PD process remain elusive, brain-derived neurotrophic factor (BDNF) is thought to exert neuroprotective as well as neurotrophic roles for the survival and differentiation of DA neurons in SN. Addressing molecular mechanisms of BDNF action in both primary embryonic mesencephalic cultures and in vivo animal models has been technically difficult because DA neurons in SN are relatively rare and present with many heterogeneous cell populations in midbrain. We have developed and characterized a DA neuronal cell line of embryonic SN origin that is more accessible to molecular analysis and can be used as an in vitro model system for studying SN DA neurons. A clonal SN DA neuronal progenitor cell line SN4741, arrested at an early DA developmental stage, was established from transgenic mouse embryos containing the targeted expression of the thermolabile SV40Tag in SN DA neurons. The phenotypic and morphological differentiation of the SN4741 cells could be manipulated by environmental cues in vitro. Exogenous BDNF treatment produced significant neuroprotection against 1-methyl-4-phenylpyridinium, glutamate, and nitric oxide-induced neurotoxicity in the SN4741 cells. Simultaneous phosphorylation of receptor tyrosine kinase B accompanied the neuroprotection. This SN DA neuronal cell line provides a unique model system to circumvent the limitations associated with primary mesencephalic cultures for the elucidation of molecular mechanisms of BDNF action on DA neurons of the SN.

1-Methyl-4-phenylpyridinium↗

PubMed1999

Loss of one but not two mdm2 null alleles alters the tumour spectrum in p53 null mice.

The transcriptional activity of the p53 tumour suppressor is inhibited by binding to MDM2. The in vivo significance of this interaction was established in mdm2 null mice. Embryonic lethality due to loss of mdm2 is completely rescued by deletion of p53, indicating that the lethality is due to inability to down-modulate p53 function. The production of mice null for both p53 and mdm2 led to an assessment of the role of MDM2 in tumour development. Tumour latency and spectrum in p53 null mice were monitored in the presence or absence of mdm2. Two unusual findings resulted: tumour latency in p53 null/mdm2 heterozygous mice was longer than in p53/mdm2 double-null mice; and the incidence of sarcomas was higher in p53 null/mdm2 heterozygous mice than in p53 null or p53/mdm2 double-null mice. These data raise the possibility that heterozygosity at the mdm2 locus in the absence of p53 affects the development of tumours of mesenchymal origin.

Animals↗

PubMed1999

Altered presynaptic gene expression in transgenic mice producing dopamine in the pineal gland.

Neurotransmitters are known to play an important role in the development of the nervous system. We recently generated transgenic mice that ectopically express tyrosine hydroxylase (TH) and thereby produce dopamine (DA) de novo in pinealocytes of the pineal gland (PG). The transgenic PG also exhibited a dramatic decrease in TH-immunoreactive (IR) fibers putatively arising from the superior cervical ganglion (SCG) (Cho et al. [1996] Proc Natl Acad Sci USA 93:2862-2866). In the current study, however, we found that there was no reduction in the number of fibers immunostained for neurofilament protein or PGP9.5, markers known to be heavily localized in fibers, despite the reduction of TH fiber density. Therefore, we investigated whether the decreased TH-IR fiber density is the consequence of reduced sympathetic innervation, or a decrease in TH expression within innervating fibers. Immunohistochemical analysis comparing control and transgenic PG demonstrated no apparent differences in numbers of NPY- and aromatic-L-amino acid decarboxylase (AADC)-IR fibers, indicating that TH expression is decreased in a normal number of innervating fibers. Furthermore, presynaptic neurons in the transgenic SCG showed abnormal and heterogeneous TH immunoreactivity and reduced TH and norepinephrine transporter (NET) mRNA levels. These results show that ectopic DA production in the PG lowers TH and NET gene expression in the SCG without altering sympathetic innervation to the PG and suggest that the alteration of target neurotransmitter phenotype may influence gene expression of phenotype-specific proteins in projecting neurons.

Animals↗

PubMed1999

Hyperthermic isolated regional perfusion for the treatment of osteosarcoma in the lower extremity.

BACKGROUND: In order to reduce the systemic toxity of cisplatin and to increase the effect on the local tumor, facilitating limb-preserving procedures, we have been using hyperthermic isolated regional perfusion (HIRP) for the treatment of osteosarcoma in addition to preoperative chemotherapy. MATERIALS AND METHODS: Twenty patients with an osteosarcoma in a lower extremity were treated with both preoperative chemotherapy and HIRP. RESULTS: The chemotherapeutic effects of preoperative chemotherapy with HIRP was grade III in 6, and grade IV (no viable cell areas observed) in 7. The surgical margins could be reduced in these 13 cases of good responders showing over 90% necrosis (grade III or grade IV), which mainly involved postnecrotic fibrosis and osteosclerosis. CONCLUSION: HIRP can help to control the tumor locally. A more conservative operation was then possible in cases of good responders to preoperative chemotherapy with HIRP.

Adolescent↗

PubMed1999

Protective role of glutathione synthesis in response to oxidized low density lipoprotein in human vascular endothelial cells.

Impairment of endothelial cells by oxidized low density lipoprotein (OxLDL) is believed to be the first step in atherogenesis. It is also believed that oxidative stress/antioxidant imbalance is involved in the cell damage by OxLDL. However, little is known about the interaction between OxLDL and antioxidants. In this study, we show that treatment of human vascular endothelial cells with OxLDL caused a gradual increase of glutathione (gamma-glutamylcysteinyl glycine, GSH) levels in 24 h. OxLDL increased the intracellular levels of reactive oxygen species (ROS) and stimulated the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for the GSH synthesis, the mitogen-activated protein kinase (MAPK) activity, and the AP-1-DNA binding activity. The luciferase activity of gamma-GCS promoter containing AP-1 site was activated by OxLDL. Collectively, OxLDL induces gamma-GCS expression mediated by AP-1 resulting in an increase of GSH levels. The MAPK activity stimulated by ROS may be involved in the activation of AP-1. The increase in GSH by OxLDL may afford cellular protection against OxLDL-induced oxidative stress.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1999

Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells.

In the present study, we show that melatonin induces the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme of glutathione (GSH) synthesis, in ECV304 human vascular endothelial cells. One micromolar melatonin induced the expression of gamma-GCS mRNA followed by an increase in the concentration of GSH with a peak at 24 h. An electrophoretic mobility shift assay showed that melatonin stimulates the DNA-binding activity of activator protein-1 (AP-1) as well as retinoid Z receptor/retinoid receptor-related orphan receptor alpha (RZR/RORalpha). ECV304 cells transiently transfected with a plasmid containing the gamma-GCS promoter-luciferase construct showed increased luciferase activity when treated with melatonin. The melatonin-dependent luciferase activity was found in the gamma-GCS promoter containing AP-1 site. The luciferase activity mediated by AP-1 was repressed in the promoter containing RZR/RORalpha site. In addition, cell cycle analysis showed that melatonin increases the number of cells in the G0/G1 phase; however, treatment of the cells with buthionine sulfoximine, a specific inhibitor of gamma-GCS, abolished the effect of melatonin on the cell cycle, suggesting induction of cell arrest by melatonin requires GSH. As conclusion, induction of GSH synthesis by melatonin protects cells against oxidative stress and regulates cell proliferation.

Buthionine Sulfoximine↗

PubMed1999

Analysis of the C-terminal region of Arabidopsis thaliana APETALA1 as a transcription activation domain.

APETALA1 (AP1) of Arabidopsis thaliana is a transcription factor controlling flower development. AP2 is a member of the MADS (MCM1, AGAMOUS, DEFICIENS, SRF) superfamily, which plays important roles in differentiation in plants and animals. MADS domains, which function most importantly in DNA binding, are found in all major eukaryotic kingdoms. In plants, MADS domain-containing proteins also possess a region of moderate sequence similarity named the K domain, which is involved in protein-protein interaction. Little is known about the function of a third, highly variable, domain designated the C domain, as it resides at the C terminus of the MADS proteins of plants. Here we report that the C-terminal domain of Arabidopsis thaliana AP1 and its homologues perform a transcriptional activation function. The C-terminal region of AP1 is composed of at least two separable transcriptional activation domains that function synergistically.

Amino Acid Sequence↗

PubMed1999

Enhanced basophil histamine release and neutrophil chemotactic activity predispose grain dust-induced airway obstruction.

BACKGROUND: The pathogenic mechanism of grain dust (GD)-induced occupational asthma (OA) remains unclear. OBJECTIVE: To understand further the mechanism of GD-induced OA. METHODS: Fifteen employees working in a same GD industry, complaining of work-related respiratory symptoms, were enrolled and were divided into two groups according to the GD-bronchoprovocation test (BPT) result: six positive responders were grouped as group III, nine negative responders as group II and five healthy controls as group I. Serum GD-specific immunoglobulin (Ig)E (sIgE), specific IgG (sIgG) and specific IgG4 (sIgG4) antibodies were detected by enzyme-linked immunosorbent assay. Basophil histamine release was measured by the autofluorometric method, and changes of serum neutrophil chemotactic activity were observed by the Boyden chamber method. RESULTS: For clinical parameters such as degree of airway hyperresponsiveness to methacholine, duration of respiratory symptoms, exposure duration, and prevalences of serum sIgE, sIgG and sIgG4 antibodies, there were no significant differences between group II and III (P > 0.05, respectively). Serum neutrophil chemotactic activity increased significantly at 30 min and decreased at 240 min after the GD-BPT in group III subjects (P < 0.05, respectively), while no significant changes were noted in group II subjects (P > 0.05). Basophil histamine release induced by GD was significantly higher in group III than those of group I or group II (P < 0.05, respectively), while minimal release of anti-IgG4 antibodies was noted in all three groups. CONCLUSIONS: These results suggest that enhanced basophil histamine release and serum neutrophil chemotactic activity might contribute to the development of GD-induced occupational asthma.

Adult↗

PubMed1999

Protein status of infants with phenylketonuria undergoing nutrition management.

OBJECTIVES: The objectives of this study were to determine if Phenex-1, amino-acid modified medical food with iron maintained normal indices of protein status in infants with phenylketonuria (PKU) and to investigate factors that influence plasma amino acid concentrations. METHODS: A study was conducted for six months in 35 infants with classical PKU diagnosed in the neonatal period. Diet diaries and plasma amino acid concentrations were obtained monthly. Blood for analysis of plasma albumin, blood urea nitrogen (BUN), retinol binding protein (RBP) and transthyretin was obtained at one, three and six months of study. RESULTS: Mean (+/-SEM) total daily intake of medical food and nutrients was 79+/-4 g; 17.3+/-0.6 g protein, 660+/-18 kcal, 255+/-10 mg phenylalanine (Phe), and 1423+/-56 mg tyrosine (Tyr). Mean concentrations of plasma amino acids, except cystine (during entire study), glycine (first month) and Phe were in the normal range. Mean concentrations of plasma Phe were in the treatment range (120 to 360 micromol/L). Plasma concentrations of arginine, methionine, Phe, tryptophan, Tyr, and valine were positively correlated with intakes at various months of study. Concentrations of aspartic and glutamic acids, Phe, and Tyr were positively correlated and 17 amino acids were negatively correlated with the interval between feeding and blood draw. At six months of study, concentration of plasma albumin was 4.1+/-0.1 g/dL, RBP was 3.74+/-0.2 mg/dL, transthyretin was 17.9+/-0.9 mg/dL, and urea nitrogen was 11.9+/-0.5 mg/dL. CONCLUSION: During study, all mean plasma indices of protein status were in normal reference ranges. Phenex-1 supports normal mean plasma amino acid, albumin, RBP, transthyretin, and BUN concentrations when fed in adequate amounts.

Amino Acids↗

PubMed1999

Regulation of gamma-glutamylcysteine synthetase expression in response to oxidative stress.

Glutathione (GSH) is synthesized by the activity of two ATP-requiring GSH synthesizing enzymes. Gamma-glutamylcysteine synthetase (gamma-GCS) is the rate limiting enzyme for the GSH synthesis. Gamma-GCS is a heterodimer of heavy, catalytic subunit and light, regulatory subunit and responsive to many stresses, such as heat shock, oxidative stress or cytokines. To know the regulation of the expression of gamma-GCS gene, in the present study, we show evidences that gamma-GCS heavy subunit is upregulated by oxidative stress by ionizing radiation and TNF-alpha mediated by nuclear factor-kappaB (NF-kappaB), and impairment of the expression of gamma-GCS by TNF-alpha in diabetic condition. Furthermore we describe the importance of GSH in the regulation of NF-kappaB subunits.

Animals↗

PubMed1999

Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells.

In this paper, we provide direct evidence that glutathione S-transferase pi (GSTpi) detoxifies cisplatin (CDDP). We used human colonic cancer HCT8 cells sensitive and resistant to CDDP, the level of cisplatin-glutathione adduct (DDP-GSH) being higher in the resistant cells. There was an overexpression of GSTpi mRNA in these CDDP-resistant cells. Incubation of the cells with CDDP resulted in the formation of DDP-GSH dependent on the CDDP concentration and the incubation time. The formation of DDP-GSH was abolished when the cells were pre-treated with ethacrynic acid or ketoprofen, inhibitors of GSTpi. Purified GSTpi also catalyzed the formation of DDP-GSH in vitro, with an apparent Km of 0.23 mM for CDDP and an apparent Vmax of 4.9 nmol/min/mg protein. The increase in DDP-GSH produced by GSTpi was linear with incubation time up to 3 h and optimal of pH 7.4. A GSTpi transfectant cell line was constructed in HCT8 cells using a pcDNA3.1 (-)/Myc-His B with an expression vector containing cDNA for GSTpi. Transfection of GSTpi cDNA into HCT8 cells resulted in an increase in the expression of GSTpi by 1.4-fold in parallel with an augmentation of the formation of DDP-GSH. These results suggest that GSTpi plays a role in the formation of DDP-GSH and the acquisition of resistance to CDDP in cancer cells.

Cisplatin↗

PubMed1999

Effects of clonidine on human middle cerebral artery flow velocity and cerebrovascular CO2 response during sevoflurane anesthesia.

The present study was designed to evaluate the effects of clonidine on human middle cerebral artery flow velocity and the cerebrovascular CO2 response during sevoflurane anesthesia using transcranial Doppler ultrasonography. The subjects were nine awake volunteers (group A) and 18 patients receiving oral preanesthetic medication of clonidine, 3-4 mcg/kg, (group C), or placebo (group S). In groups C and S, anesthesia was induced with inhalation of sevoflurane-nitrous oxide. After tracheal intubation, anesthesia was maintained with 2% end-tidal sevoflurane alone. In group A, each volunteer wore a nose clip and breathed through a mouthpiece using a Mapleson D breathing system. The time-mean middle cerebral artery flow velocity (Vmca) was measured during hypocapnia, normocapnia, and hypercapnia. In groups S and C, the Vmca values were significantly lower than those of group A at each PaCO2 level. The Vmca value of group C was significantly lower than that of group S in hypercapnia, but not in hypocapnia or normocapnia. The CO2 response slope of group C was significantly lower than those of groups A and S. The results indicate that clonidine, administered as an oral preanesthetic medication, reduces Vmca in hypercapnia but not in hypocapnia or normocapnia, and reduces the cerebrovascular CO2 response during sevoflurane anesthesia.

Adrenergic alpha-Agonists↗

PubMed1999

Clinical and histopathological characteristics of basal cell carcinoma in Korean patients.

Seventy-eight Korean patients with basal cell carcinoma (BCC) between 1984 and 1998 were retrospectively examined at Ewha Womans University Tongdaemun Hospital, Seoul, Korea. We analyzed the annual incidence, age and sex distribution, site of the lesions, clinical appearance, including the proportion of clinically pigmented tumors, modalities of treatment, incidence of recurrence and metastasis of the tumors, the histopathological patterns, and whether solar elastosis, microscopic pigmentation, or adamantinoid feature were associated. The male-to-female ratio was 0.902, and the average age of the patients at first examination was 58.2 years. Eighty percent of the tumors occurred on the head and neck, most commonly on the nose (26.9%), followed by the cheek, eyelid, and upper lip. Ulcerated nodules were the most common clinical presentation. Clinically, 55% of the tumors were pigmented. Six tumors recurred; none metastasized. Surgical excision was the most common modality of treatment. The most frequent histopathological pattern was the solid type (60.3%), followed by the superficial (11.5%) and fibrosing (9.0%) types. The occurrence of the superficial type was significantly associated with truncal lesions (p < 0.001). Solar elastosis was present in 62.1% of the tumors on the head and neck, compared with 8.3% in those of the trunk and limbs (p < 0.001), indicating the significance of sun exposure in the pathogenesis of BCC on exposed areas. Microscopic pigmentation was seen in 69.2% of the tumors. The focal adamantinoid feature was found in 14.1%, which is much higher than the previously reported incidence.

Adolescent↗

PubMed1999

Growth of newborn, term infants fed soy formulas for 1 year.

Few studies have measured long-term growth in infants fed soy protein-based formulas. The effect of nucleotide (NT) supplementation of soy protein-based infant formulas on growth is unknown. Growth was therefore evaluated in healthy term infants fed a soy protein-based formula (SOY; n = 73), SOY with added NT (72 mg added NT/L) at human milk (HM) levels (SOYN, n = 73), or mixed feeding (MF, n = 67) in a randomized, masked, parallel 1-year feeding study. The MF group (a nonrandomized reference group) was fed HM exclusively from birth to 2 months of age followed by HM and/or a standard milk-based formula (Similac with Iron with no supplemental NTs) to 1 year of age. Results indicated that growth (weight, length, and head circumference) was normal and comparable among the three groups. All three groups had similar plasma albumin (at 2 months of age) and hemoglobin levels (at 12 months of age). Thus, this study demonstrated similar growth in the first year of life among infants fed MF feeding or soy formula with or without supplemental NTs.

Age Factors↗