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Articles by S. W Kim
Total Records ( 8 ) for S. W Kim
  J. S You , S. W Kim , H. S Lee and S. P. Chung
 

Diffusion-weighted MRI, a type of MR technique that can distinguish between cerebral fat embolism and diffuse axonal injury, is presented in this report. Emergency physicians should consider using diffusion-weighted imaging in unconscious trauma patients when their brain CT scans are unremarkable.

  T. N Chung , S. W Kim , Y. S Park and I. Park
 

Methanol is generally known to cause visual impairment and various systemic manifestations. There are a few reported specific findings for methanol intoxication on magnetic resonance imaging (MRI) of the brain. A case is reported of unilateral blindness with third cranial nerve palsy oculus sinister (OS) after the ingestion of methanol. Unilateral damage of the retina and optic nerve were confirmed by fundoscopy, flourescein angiography, visual evoked potential and electroretinogram. The optic nerve and extraocular muscles (superior rectus, medial rectus, inferior rectus and inferior oblique muscle) were enhanced by gadolinium-DTPA on MRI of the orbit. This is the first case report of permanent monocular blindness with confirmed unilateral damage of the retina and optic nerve, combined with third cranial nerve palsy after methanol ingestion.

  A. L Brunner , D. S Johnson , S. W Kim , A Valouev , T. E Reddy , N. F Neff , E Anton , C Medina , L Nguyen , E Chiao , C. B Oyolu , G. P Schroth , D. M Absher , J. C Baker and R. M. Myers
 

To investigate the role of DNA methylation during human development, we developed Methyl-seq, a method that assays DNA methylation at more than 90,000 regions throughout the genome. Performing Methyl-seq on human embryonic stem cells (hESCs), their derivatives, and human tissues allowed us to identify several trends during hESC and in vivo liver differentiation. First, differentiation results in DNA methylation changes at a minimal number of assayed regions, both in vitro and in vivo (2%–11%). Second, in vitro hESC differentiation is characterized by both de novo methylation and demethylation, whereas in vivo fetal liver development is characterized predominantly by demethylation. Third, hESC differentiation is uniquely characterized by methylation changes specifically at H3K27me3-occupied regions, bivalent domains, and low density CpG promoters (LCPs), suggesting that these regions are more likely to be involved in transcriptional regulation during hESC differentiation. Although both H3K27me3-occupied domains and LCPs are also regions of high variability in DNA methylation state during human liver development, these regions become highly unmethylated, which is a distinct trend from that observed in hESCs. Taken together, our results indicate that hESC differentiation has a unique DNA methylation signature that may not be indicative of in vivo differentiation.

  B Kim , Y Lee , Y Kim , K. H Lee , S Chun , K Rhee , J. T Seo , S. W Kim and J. S. Paick
  BACKGROUND

DAZ is a male infertility gene located at the AZFc region of the Y chromosome. There are four copies of the DAZ gene that share a strong homology but are not identical to one another. In the present study, we carried out cDNA cloning and immunoblot analyses to determine whether all of the DAZ genes are actively expressed in the human testis.

METHODS

AZFc deletion was detected by sequence-tagged site polymerase chain reaction (PCR) of genomic DNA isolated from blood samples. DAZ cDNAs were cloned with RT–PCR followed by sequence analysis. The expression of DAZ proteins in human testis was determined by immunoblot and compared with DAZ cDNA expression.

RESULTS

Immunoblot analysis revealed four DAZ protein bands in testis samples that showed no deletions in the AZFc region. No specific bands were observed in samples from AZFc deletion patients. Testis samples from individuals with the partial AZFc deletion, gr/gr, showed two DAZ-specific bands. Interestingly, the sizes of DAZ-specific bands varied among individuals. Analysis of DAZ transcripts in testis samples revealed that the DAZ proteins were translated from the largest of the multiple transcripts originating from each single DAZ gene.

CONCLUSIONS

All four DAZ genes are expressed in the human testis, and their products are highly polymorphic among men.

  J. W Lee , H. D Han , M. M. K Shahzad , S. W Kim , L. S Mangala , A. M Nick , C Lu , R. R Langley , R Schmandt , H. S Kim , S Mao , J Gooya , C Fazenbaker , D Jackson , D. A Tice , C. N Landen , R. L Coleman and A. K. Sood
  Background

EphA2 is overexpressed in many types of human cancer but is absent or expressed at low levels in normal epithelial tissues. We investigated whether a novel immunoconjugate containing an anti-EphA2 monoclonal antibody (1C1) linked to a chemotherapeutic agent (monomethyl auristatin phenylalanine [MMAF]) through a noncleavable linker maleimidocaproyl (mc) had antitumor activity against ovarian cancer cell lines and tumor models.

Methods

Specificity of 1C1-mcMMAF was examined in EphA2-positive HeyA8 and EphA2-negative SKMel28 ovarian cancer cells by antibody binding and internalization assays. Controls were phosphate-buffered saline (PBS), 1C1, or control IgG-mcMMAF. Viability and apoptosis were investigated in ovarian cancer cell lines and tumor models (10 mice per group). Antitumor activities were tested in the HeyA8-luc and SKOV3ip1 orthotopic mouse models of ovarian cancer. Endothelial cells were identified by use of immunohistochemistry and anti-CD31 antibodies. All statistical tests were two-sided.

Results

The 1C1-mcMMAF immunoconjugate specifically bound to EphA2-positive HeyA8 cells but not to EphA2-negative cells and was internalized by HeyA8 cells. Treatment with 1C1-mcMMAF decreased the viability of HeyA8-luc cells in an EphA2-specific manner. In orthotopic mouse models, treatment with 1C1-mcMMAF inhibited tumor growth by 85%–98% compared with that in control mice (eg, for weight of HeyA8 tumors, 1C1-mcMMAF = 0.05 g and control = 1.03 g; difference = 0.98 g, 95% confidence interval [CI] = 0.40 to 1.58 g; P = .001). Even in bulkier disease models with HeyA8-luc cells, 1C1-mcMMAF treatment, compared with control treatment, caused regression of established tumors and increased survival of the mice (eg, 1C1-mcMMAF vs control, mean = 60.6 days vs 29.4 days; difference = 31.2 days, 95% CI = 27.6 to 31.2 days; P = .001). The antitumor effects of 1C1-mcMMAF therapy, in SKOV3ip1 tumors, for example, were statistically significantly related to decreased proliferation (eg, 1C1-mcMMAF vs control, mean = 44.1% vs 55.8% proliferating cells; difference = 11.7%, 95% CI = 2.45% to 20.9%; P = .01) and increased apoptosis of tumor cells (eg, 1C1-mcMMAF vs control, mean = 8.6% vs 0.9% apoptotic cells; difference = 7.7%, 95% CI = 3.8% to 11.7%; P < .001) and of mouse endothelial cells (eg, 1C1-mcMMAF vs control, mean 2.8% vs 0.4% apoptotic endothelial cells; difference = 2.4%, 95% CI = 1.4% to 4.6%; P = .034).

Conclusion

The 1C1-mcMMAF immunoconjugate had antitumor activity in preclinical models of ovarian carcinoma.

  T Lee , S. W Kim , W. P Chisholm , J Slaven and M. Harper
 

The American Conference of Governmental Industrial hygienists (ACGIH) lowered the threshold limit value (TLV) for respirable crystalline silica (RCS) exposure from 0.05 to 0.025 mg m–3 in 2006. For a working environment with an airborne dust concentration near this lowered TLV, the sample collected with current standard respirable aerosol samplers might not provide enough RCS for quantitative analysis. Adopting high flow rate sampling devices for respirable dust containing silica may provide a sufficient amount of RCS to be above the limit of quantification even for samples collected for less than full shift. The performances of three high flow rate respirable samplers (CIP10-R, GK2.69, and FSP10) have been evaluated in this study. Eleven different sizes of monodisperse aerosols of ammonium fluorescein were generated with a vibrating orifice aerosol generator in a calm air chamber in order to determine the sampling efficiency of each sampler. Aluminum oxide particles generated by a fluidized bed aerosol generator were used to test (i) the uniformity of a modified calm air chamber, (ii) the effect of loading on the sampling efficiency, and (iii) the performance of dust collection compared to lower flow rate cyclones in common use in the USA (10-mm nylon and Higgins–Dewell cyclones). The coefficient of variation for eight simultaneous samples in the modified calm air chamber ranged from 1.9 to 6.1% for triplicate measures of three different aerosols. The 50% cutoff size (50dae) of the high flow rate samplers operated at the flow rates recommended by manufacturers were determined as 4.7, 4.1, and 4.8 µm for CIP10-R, GK2.69, and FSP10, respectively. The mass concentration ratio of the high flow rate samplers to the low flow rate cyclones decreased with decreasing mass median aerodynamic diameter (MMAD) and high flow rate samplers collected more dust than low flow rate samplers by a range of 2–11 times based on gravimetric analysis. Dust loading inside the high flow rate samplers does not appear to affect the particle separation in either FSP10 or GK2.69. The high flow rate samplers overestimated compared to the International Standards Organization/Comité Européen de Normalisation/ACGIH respirable convention [up to 40% at large MMAD (27.5 µm)] and could provide overestimated exposure data with the current flow rates. However, both cyclones appeared to be able to provide relatively unbiased assessments of RCS when their flow rates were adjusted.

  J. E Grant , C. B Donahue , B. L Odlaug , S. W Kim , M. J Miller and N. M. Petry
 

Sixty-eight individuals were randomised to either six sessions of imaginal desensitisation plus motivational interviewing (IDMI) or Gamblers Anonymous. Individuals assigned to IDMI had significantly greater reductions in Yale–Brown Obsessive Compulsive Scale Modified for Pathological Gambling total scores, gambling urges and gambling behaviour. People who failed to respond to Gamblers Anonymous reported significantly greater reduction in pathological gambling symptoms following later assignment to IDMI. Abstinence was achieved by 63.6% during the acute IDMI treatment period.

  Y. S Kim , N. H Kim , S. J Yeom , S. W Kim and D. K. Oh
 

Codon optimization was used to synthesize the blh gene from the uncultured marine bacterium 66A03 for expression in Escherichia coli. The expressed enzyme cleaved β-carotene at its central double bond (15,15') to yield two molecules of all-trans-retinal. The molecular mass of the native purified enzyme was ~64 kDa as a dimer of 32-kDa subunits. The Km, kcat, and kcat/Km values for β-carotene as substrate were 37 µm, 3.6 min–1, and 97 mm–1 min–1, respectively. The enzyme exhibited the highest activity for β-carotene, followed by β-cryptoxanthin, β-apo-4'-carotenal, -carotene, and -carotene in decreasing order, but not for β-apo-8'-carotenal, β-apo-12'-carotenal, lutein, zeaxanthin, or lycopene, suggesting that the presence of one unsubstituted β-ionone ring in a substrate with a molecular weight greater than C35 seems to be essential for enzyme activity. The oxygen atom of retinal originated not from water but from molecular oxygen, suggesting that the enzyme was a β-carotene 15,15'-dioxygenase. Although the Blh protein and β-carotene 15,15'-monooxygenases catalyzed the same biochemical reaction, the Blh protein was unrelated to the mammalian β-carotene 15,15'-monooxygenases as assessed by their different properties, including DNA and amino acid sequences, molecular weight, form of association, reaction mechanism, kinetic properties, and substrate specificity. This is the first report of in vitro characterization of a bacterial β-carotene-cleaving enzyme.

 
 
 
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