Biomedical subjects

W S Choi

Publications and source records attributed to W S Choi.

At least 19 recordsLinked to original sources

PubMed2006

Associations of serum minerals with body mass index in adult women.

OBJECTIVE: This cross-sectional study evaluated the association between serum minerals and body mass index in adult women. METHODS: One hundred and eighteen adult women were recruited by written advertisement from outpatient clinics or a health promotion center at a university hospital. Serum calcium, magnesium, copper and zinc were measured by an automatic analytical instrument and body mass index was calculated from height and weight. RESULTS: Serum magnesium was inversely associated with body mass index (beta=-0.283, P=0.001) whereas serum copper had a positive association with body mass index (beta=0.197, P=0.025) after adjusting for age, physical activity, energy intake, dietary fat, alcohol consumption, supplements and menopause status. No associations were found with serum calcium and zinc. CONCLUSION: Serum magnesium and copper may be involved in the regulation of body size in adult women.

Adult↗

PubMed2005

Expression of 14-3-3 zeta and interaction with protein kinase C in the rat retina in early diabetes.

AIMS/HYPOTHESIS: The present study aimed to investigate the expression levels of and the relationship between 14-3-3 zeta and protein kinase C (PKC) in the retina of early diabetes. METHODS: Changes in the expression levels of, and interaction between, 14-3-3 zeta and PKC were investigated by Northern and Western blot analyses, immunoprecipitation and double immunostaining in the retina of diabetic rats after 6 weeks of diabetes. PKC activity was examined using a PKC assay. RESULTS: In the diabetic retina, the molecular levels of 14-3-3 zeta were reduced, while those of PKC beta and zeta were increased. Direct interaction between 14-3-3 zeta and PKC was markedly decreased in the retina after 6 weeks of diabetes, while PKC activity was increased. CONCLUSIONS/INTERPRETATION: These findings show that a reduction in 14-3-3 zeta can induce PKC activation, suggesting that this is a main cause of visual dysfunction in the retina during diabetes.

14-3-3 Proteins↗

PubMed2004

Concomitant reconstruction of mandibular basal and alveolar bone with a free fibular flap.

Repair of long-span mandibular defects with a free fibular flap is now a routine procedure. However, the bone height of the neo-mandible after reconstruction with a fibular flap is about half that of the dentulous mandible. When a fibular graft is placed only at the inferior border of the mandible, the resulting vertical discrepancy between the graft segment and the occlusal plane can adversely affect implant mechanics or denture stability and retention. To overcome these problems, we developed a technique for two-strut type mandibular reconstruction. A vascularized fibular segment is used to reconstruct the inferior basal portion of the neo-mandible, while a non-vascularized residual fibular segment is used to simulate the superior alveolar portion. We used this technique in 22 patients. Graft survival, graft resorption, and the ability to place implants were assessed as compared with those after the conventional one-strut type technique. The fibular segment grafted to the alveolar region was removed in one patient with intraoral wound dehiscence and in two with postoperative infection. All vascularized fibular flaps were successful. The resorption rate was 13.6+/-7.2% for non-vascularized segments and 3.0+/-3.7% for vascularized segments. Dental implants were placed in five of our 22 patients. The crown:fixture length ratio was improved to 1:1.7, as compared with a ratio of 1:1.21 with use of a conventional fibular flap. We conclude that our technique is very easy and safe and provides substantially improved lower-lip and cheek support and implant-prosthetic mechanics than conventional procedures for the repair of long-span mandibular defects.

Adult↗

PubMed2001

Temporal and spatial expression of neurotrophins and their receptors during male germ cell development.

Spermatogenesis is a stepwise cellular differentiation process involving proliferation and commitment to differentiate in spermatogonia, meiosis in spermatocytes, and morphological changes in round spermatids. The whole process is regulated by intercellular communication between the germ cells and the supporting cells. In order to investigate whether neurotrophin family and their receptors contribute to the intercellular communication, we examined the expression of neurotrophins and their receptors in testis during spermatogenesis. One of neurotrophin family, NT-3 was expressed in spermatocytes and spermatogonia while its high affinity receptor, TrkC was found mainly in late spermatids and their low affinity receptor, TrkA in spermatocytes and round spermatids. On the other hand, BDNF immunoreactivity was found in Sertoli cells while its high affinity receptor, TrkB was found in spermatogonia. The temporally and spatially regulated expression of neurotrophins, NT-3 and BDNF, and their receptors, TrkC and TrkB, during male germ cell development suggests that neurotrophins play as the paracrine factors in the intercellular communication between the germ cells and the supporting somatic cells to control germ cell development.

Animals↗

PubMed2001

Low-density cDNA array-coupled to PCR differential display identifies new estrogen-responsive genes during the postnatal differentiation of the rat hypothalamus.

To identify estrogen (E)-responsive genes that may play important roles in the sexual differentiation and maturation of the neuroendocrine hypothalamus, we used mRNA differential display PCR to analyze hypothalamic RNA derived from estrogen-sterilized rats (ESRs). Neonatal rats were s.c.-injected with 100 microg of 17 beta-estradiol-benzoate (EB) for 5 days. Approximately 300 out of more than 2000 RNAs examined displayed a differential expression pattern between hypothalami of the ESR females compared to their 60-day-old controls. EB-dependent expression of these genes was further analyzed by low-density cDNA array using cDNA probe sets reverse-transcribed from the same groups; 98 genes were confirmed to be differentially expressed. We selected 41 clones that showed higher density differences between the two probe sets than mean density difference in control cyclophilin cDNA blots in the cDNA array. After being cloned into pGEM-T vectors, their sequences were analyzed. Homology searches identified four genes as a protein kinase C (PKC)-binding protein, NELL2 (clone 6-1), a thyroid nuclear factor, TTF-1 (9-1), Munc18-1 (17-6), and leuserpin-2 (18-5). The other 22 genes were similar to reported genes or cDNAs such as mouse kinesin-associated protein 3 (KAP3, 8b), mouse IgE binding lectin (15-1), normalized rat brain cDNA (5-1), rat cDNA (8-1) and rat embryonic cDNA (17-1). Fifteen clones such as clone 7-3 showed no match in the GenBank Database. Further characterization of eight clones (17-1, 7-3, 8-1, 5-1, NELL2, KAP3 homolog, IgE binding lectin homolog, and TTF-1) showed that their expression in the adult female rat hypothalamus is sensitive to neonatal treatment with EB. They showed brain-specific expression and moreover, showed an increase in their mRNA level before the initiation of puberty. Some of them showed gender differences in their different postnatal expression pattern. We speculate that further study will demonstrate that many of the E-regulated genes identified in the present study play important roles in the regulation of the sexual differentiation and E-dependent maturation of the hypothalamus.

Animals↗

PubMed2001

Temporospatial sequence of cellular events associated with etoposide-induced neuronal cell death: role of antiapoptotic protein Bcl-X(L).

Etoposide-induced death comprises such nuclear events as the formation of topoisomerase II-DNA cleavable complex and cytosolic events including caspase activation. By first establishing the temporospatial death sequence triggered by etoposide in a neuronal cell line, MN9D overexpressing Bcl-X(L) (MN9D/Bcl-X(L)) or control vector (MN9D/Neo), we examined whether formation of this complex is primarily responsible for cell death and at which strategic points and how Bcl-X(L) blocks etoposide-induced neuronal death. Etoposide induced death that was dependent on caspase, cycloheximide, and calpain in MN9D/Neo cells. Etoposide also induced death in enucleated MN9D/Neo cells, although this was less severe. The level of topoisomerase II-DNA cleavable complex reached at a maximum of 2 hr after etoposide treatment was identical in MN9D/Neo and MN9D/Bcl-X(L) cells. In MN9D/Neo cells, cytochrome c release into the cytosol and caspase activation occurred as early as 2 hr and 3-6 hr after etoposide treatment, respectively. Etoposide-induced DNA laddering potentially via caspase appeared as early as 12 hr after drug treatment, followed by nuclear swelling in MN9D/Neo cells (>18-20 hr). Subsequently, nuclear condensation started by 24-28 hr and became apparent thereafter. All of these events except for nuclear swelling were substantially blocked in MN9D/Bcl-X(L). At the later stage of cell death (<32-36 hr), a specific cleavage of Bax and fodrin appeared that was completely blocked by calpain inhibitor or by Bcl-X(L). Taken together, our data suggest that Bcl-X(L) prevents etoposide-induced neuronal death by exerting its anticaspase and anticalpain effect on cellular events after the formation of topoisomerase II-DNA cleavable complex that may not be a major contributor to cell death.

Apoptosis↗

PubMed2001

Overexpression of calbindin-D28K induces neurite outgrowth in dopaminergic neuronal cells via activation of p38 MAPK.

An MN9D dopaminergic neuronal cell line overexpressing calbindin-D28K (MN9D/Calbindin) was established in order to investigate directly the potential role of calcium-binding protein in neuronal differentiation. Overexpression of calbindin-D28K in MN9D cells resulted in significant increases in the number of neurites, the length of primary neurites, and the total extent of neurites. This robust neurite outgrowth occurred without cessation of cell division. Analysis of immunoblots revealed that this morphological differentiation was accompanied by increased expression of such markers of maturation as the synaptosomal protein SNAP-25. During calbindin-D28K-evoked neurite outgrowth in MN9D cells, phosphorylation of p38 mitogen-activated protein kinase (MAPK) dramatically increased while the levels and extent of phosphorylation of such other MAPKs as c-Jun N-terminal kinase (JNK) or extracellular response kinase (ERK) were not altered. Consequently, calbindin-D28K-induced neurite outgrowth was largely abolished by treatment with a p38 inhibitor, PD 169316, while the level of SNAP-25 in MN9D/Calbindin cells was not altered by this treatment. These data support an idea that calbindin-D28K and its associated p38 signaling pathway play a role in dopaminergic neuronal differentiation.

Animals↗

PubMed2001

Inhalation delivery of proteins from ethanol suspensions.

To circumvent inherent problems associated with pulmonary administration of aqueous-solution and dry-powder protein drugs, inhalation delivery of proteins from their suspensions in absolute ethanol was explored both in vitro and in vivo. Protein suspensions in ethanol of up to 9% (wt/vol) were readily aerosolized with a commercial compressor nebulizer. Experiments with enzymic proteins revealed that nebulization caused no detectable loss of catalytic activity; furthermore, enzyme suspensions in anhydrous ethanol retained their full catalytic activity for at least 3 weeks at room temperature. With the use of Zn(2+)-insulin, conditions were elaborated that produced submicron protein particles in ethanol suspensions. The latter (insulin/EtOH) afforded respirable-size aerosol particles after nebulization. A 40-min exposure of laboratory rats to 10 mg/ml insulin/EtOH aerosols resulted in a 2-fold drop in the blood glucose level and a marked rise in the serum insulin level. The bioavailability based on estimated deposited lung dose of insulin delivered by inhalation of ethanol suspension aerosols was 33% (relative to an equivalent s.c. injection), i.e., comparable to those observed in rats after inhalation administration of dry powder and aqueous solutions of insulin. Inhalation of ethanol in a relevant amount/time frame resulted in no detectable acute toxic effects on rat lungs or airways, as reflected by the absence of statistically significant inflammatory or allergic responses, damage to the alveolar/capillary barrier, and lysed and/or damaged cells.

Administration, Inhalation↗

PubMed2001

MPP(+) downregulates mitochondrially encoded gene transcripts and their activities in dopaminergic neuronal cells: protective role of Bcl-2.

The effects of neurotoxins on levels of mitochondrially encoded gene transcripts in a dopaminergic neuronal cell line, MN9D, were examined following treatment with 200 microM N-methyl-4-phenylpyridinium (MPP(+)) or 6-hydroxydopamine (6-OHDA). As confirmed by a Northern blot analysis, levels of cytochrome c oxidase subunit 3 (COX III) and ATPase subunit 6 (ATPase 6) transcript were decreased in a time-dependent manner following treatment with MPP(+) but not with 6-OHDA. Accordingly, enzymatic activity of cytochrome c oxidase (COX) and the intracellular ATP content were also decreased in MPP(+)-treated cells while these remained unaltered in 6-OHDA-treated cells. In the cell death paradigm induced by MPP(+), overexpression of Bcl-2 in MN9D cells (MN9D/Bcl-2) significantly blocked MPP(+)-induced downregulation of COX III and ATPase 6 transcripts. In MN9D/Bcl-2 cells, MPP(+)-induced downregulation of COX activity and the intracellular level of ATP was also blocked. Treatment with a pan-caspase inhibitor, however, neither prevented MPP(+)-induced downregulation of COX activity nor affected intracellular level of ATP in MN9D cells. Taken together, our present data suggest that Bcl-2 may play a regulatory role in energy metabolism by preventing downregulation of mitochondrially encoded gene(s) at a point distinct from its known anticaspase activity in MPP(+)-induced dopaminergic neuronal death.

1-Methyl-4-phenylpyridinium↗

PubMed2001

Ethanol decreases the expression of mitochondrial cytochrome c oxidase mRNA in the rat.

To evaluate the molecular and cellular bases of effects of ethanol on the brain, we utilized a differential display-polymerase chain reaction. Several cDNA fragments were differentially expressed in the hippocampus of control vs. ethanol-treated rats. One of these genes was homologous to the rat mitochondrial cytochrome c oxidase mRNA. Northern blot analysis revealed that the expression of this message in the whole hippocampus was clearly lower after ethanol treatment. Using in situ hybridization, we also found that cytochrome c oxidase mRNA expression, especially in the CA1 and CA3 of the hippocampal regions, was significantly decreased by ethanol treatment. As cytochrome c oxidase is related to oxidative stress, the present study suggests that ethanol might affect the brain through modulation of an oxidative stress reaction.

Animals↗

PubMed2001

Synthesis and biological evaluation of novel A-ring modified hexacyclic camptothecin analogues.

Eleven A-ring modified hexacyclic analogues of camptothecin (CPT) containing a 1,4-oxazine ring were synthesized from 10-hydroxycamptothecin (11a) and 7-ethyl-10-hydroxycamptothecin (3) (SN-38) in four to five steps and were subjected to the biological tests such as cytotoxicity, topoisomerase I (Topo I) inhibitory activity, acetylcholinesterase (AChE) inhibition, and stability in human plasma. Four compounds 15a, 15b, 16a, and 16c were about 2-fold more potent than topotecan and as potent as CPT toward human cancer cell lines A549, H128, WiDr, MKN45, SK-OV-3, and SK-BR-3 in vitro, even though the most active compound 15b was slightly less potent than SN-38. The potency of Topo I inhibition of these compounds showed relatively good correlation with their cytotoxicity. Most of the compounds exhibited AChE inhibitory activity weaker (9 +/- 2 to 20 +/- 3%) than CPT (23 +/- 5%) or topotecan (20 +/- 4%) and similar to SN-38 (13 +/- 2%), indicating that they might have little effect on causing early diarrhea. The stability of lactone forms of these compounds in human plasma seemed to be much higher than that of CPT and similar to that of topotecan but lower than that of SN-38. Among the new hexacyclic CPT analogues, compound 15b showed higher antitumor activity against human tumor xenograft, WiDr, in nude mice compared to that of SN-38. The most promising compound 15b has been selected for further development.

Animals↗

PubMed2001

The localization of dopamine D2 receptor mRNA in the human placenta and the anti-angiogenic effect of apomorphine in the chorioallantoic membrane.

While there are some reports indicating that dopamine (DA) and D2-like receptors (Rc) are detected in human placenta, there is little evidence available regarding the function of DA or the precise localization of its receptors in this organ. In the present study, we confirmed the placental expression of DA D2 Rc transcripts by Northern blot analysis. Using in situ hybridization, we also first revealed that DA D2 Rc mRNA was expressed in cytotrophoblasts, syncytial trophoblasts, vascular endothelial cells, Hafbauer cells, and fibroblasts in the chorionic villi of the human placenta. The expression sites of DA D2 Rc mRNA led us to suspect other functions of DA in the placenta besides the regulation of human placental lactogen. Since the cells expressing DA D2 Rc mRNA are related to proliferation and remodeling of placental tissue, we tried to evaluate a possible involvement of DA in the regulation of placental angiogenesis. To this end, we used the chicken chorioallantoic membrane (CAM) assay. In CAM assay, apomorphine, a potent nonselective agonist of DA, has an anti-angiogenic effect. These results suggest that DA may regulate the vascularization of human placenta through its receptors present in the chorionic villi.

Allantois↗

PubMed2001

Fumigant toxicity of volatile natural products from Korean spices and medicinal plants towards the rice weevil, Sitophilus oryzae (L).

The fumigant toxicity of various volatile constituents of essential oils extracted from sixteen Korean spices and medicinal plants towards the rice weevil, Sitophilus oryzae L (Coleoptera: Curculionidae), was determined. The most potent toxicity was found in the essential oil from Mentha arvensis L. var piperascens (LC50 = 45.5 microliters litre-1 air). GC-MS analysis of essential oil from M arvensis showed it to be rich in menthol (63.2%), menthone (13.1%) and limonene (1.5%), followed in abundance by beta-pinene (0.7%), alpha-pinene (0.6%) and linalool (0.2%). Treatment of S oryzae with each of these terpenes showed menthone to be most active (LC50 = 12.7 microliters litre-1 air) followed by linalool (LC50 = 39.2 microliters litre-1 air) and alpha-pinene (LC50 = 54.9 microliters litre-1 air). Studies on inhibition of acetylcholinesterase activity of S oryzae showed menthone to have a nine-fold lower inhibitory effect than menthol, despite menthone being 8.1-fold more toxic than menthol to the rice weevil. Different modes of toxicity of these monoterpenes towards S oryzae are discussed.

Acetylcholinesterase↗

PubMed2001

Persistence of depressive symptoms in adolescents.

To examine factors related to the persistence of depressive symptoms, we used a longitudinal follow-up survey of 1,176 adolescents aged 12 to 18 in the United States who reported notable depressive symptoms at baseline. Adolescents were interviewed by telephone at baseline in 1989 and at follow-up in 1993. The outcome of interest was a self-report measure of depressive symptoms experienced within the past 12 months at follow-up. Overall, 38.5% of adolescents reported persistent depressive symptoms. Marked gender differences were found, with 44.5% of girls reporting notable depressive symptoms at follow-up compared with 28.2% for boys. Moreover, current established smokers or experimenters were significantly more likely to report notable depressive symptoms compared with never smokers (42.2%, 41.4% and 33.6%, respectively). Significant multivariate predictors of notable depressive symptoms at follow-up were female gender, change in sleep problems from 1989 to 1993, change in cigarette smoking status from 1989 to 1993, engaging in physical fights, and lack of participation in sports. Many adolescents report continued depressive symptoms over a period spanning four years. Several predictors of persistent depression were identified that could be important components of interventions targeting depressed adolescents.

Adolescent↗

PubMed2001

Synthesis and phosphodiesterase 5 inhibitory activity of novel phenyl ring modified sildenafil analogues.

New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a--d and 7a--d, were efficiently synthesized from the readily available starting materials, 1a--d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2--3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12--16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a--d and 7a--d. In the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100--200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2001

Synthesis and phosphodiesterase 5 inhibitory activity of new 5-phenyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one derivatives containing an N-acylamido group phenyl ring.

New sildenafil analogues with an N-acylamido group at the 5'-position of the phenyl ring, 6a--e, were prepared from the readily available starting compound 2 in four straightforward steps. Enzyme assays demonstrated that all the target compounds 6a-e showed higher PDE5 inhibitory activities than sildenafil. It was observed that the PDE5 inhibitory activity was enhanced as the chain length of R group increased, but introduction of the branched alkyl groups such as isopropyl (6d) and cyclohexyl (6e) resulted in the drop of potency compared with 6c. In particular the N-butyrylamido derivative 6c exhibited the highest PDE5 inhibitory activity, and was about 6-fold more potent than sildenafil. However, all the compounds exhibited somewhat weak selectivity (1--3-fold) over PDE6, indicating that the compounds 6a--e have intrinsically lower selectivity than sildenafil.

Phosphodiesterase Inhibitors↗

PubMed2001

Synthesis and phosphodiesterase inhibitory activity of new sildenafil analogues containing a carboxylic acid group in the 5'-sulfonamide moiety of a phenyl ring.

New sildenafil analogues possessing a carboxylic acid group in the 5'-sulfonamide of the phenyl ring, 9a-l, were prepared from the readily available starting compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme assays, it has been shown that all the target compounds 9a-l proved to be more potent in inhibiting phosphodiesterase type 5 (PDE5) than sildenafil by 4-38-fold. The effects on the IC(50) values were investigated by varying the alkoxy group (R) of the phenyl ring, the sulfonamide type (X), and the length of the methylene chain linking the carboxylic acid, and the results were discussed in detail. From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5 inhibitory activity and comparable to better selectivity over PDE isozymes in comparison with sildenafil, has been selected for more detailed biological investigations.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2001

Determining the probability of future smoking among adolescents.

AIMS: To determine whether the probability of future current established smoking among adolescents is related to both previous smoking experience and cognitions regarding future smoking. DESIGN, SETTING AND PARTICIPANTS: The analyses used two principal datasets: (1) a US longitudinal sample of 7960 adolescents 12-18 years old in 1989 reinterviewed at 15-22 years in 1993, (2) a California longitudinal sample of 3376 adolescents 12-17 years old in 1993 reinterviewed at 15-20 years in 1996. MEASURES: Previous smoking experience was categorized as never smoked, puffed, non-recent or recent experimenting, and non-recent or current established smoking (> or = 100 cigarettes in life-time). Smoking intentions and efficacy expectations were used to classify adolescents as having low- or high-risk cognitions. FINDINGS: High-risk cognitions (HRCs) increased the probability of future current established smoking (FCES) within each level of previous smoking experience over low-risk cognitions (LRCs); the probability of FCES for those with LRCs was about the same as those in the previous experience group with HRCs. In the US sample, the 4-year probability of FCES ranged from 5.6% for committed never smokers (with LRCs) to 83.0% for current established smokers with HRCs. Development of HRCs among middle-school never smokers occurred rapidly through age 14 years. However, current established smoking did not increase until age 14 years and stabilized by age 19 years. Where sample size was sufficient, these findings were validated in the California sample. CONCLUSIONS: Effective prevention programs should aim to convert HRCs to LRCs regardless of past behavior, particularly among middle-school never smokers and high-school experimenters.

Adolescent↗