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Biomedical subjects

Y Kim

Publications and source records attributed to Y Kim.

At least 397 records · Page 22Linked to original sources

The effect of organic solvents on the determination of cyclic boronates of some beta-blockers by gas chromatography/mass spectrometry.

Formation cyclic boronates for beta-blockers, by use of triethylamine (TEA) and pyridine as catalysts, gives more effective product yield. Eleven beta-blockers, formed by cyclic boronation with n-butylboronic acid and TEA, produced higher yields than by on-column thermal reaction and seven beta-blockers were shown to give the highest yields in the phenyl cyclic boronation with pyridine or TEA by on-column thermal and general reaction. The phenyl cyclic boronate of nadolol produced one peak in the chromatogram and the n-butyl cyclic boronate showed two peaks. On-column derivatization and n-butylboronic acid and pyridine was effective in saving analysis time and for convenience, even though some n-butyl cyclic boronates by cyclic boronation with TEA gave a better yield. In n-butyl cyclic boronation with pyridine by on-column thermal reaction the detection limits were 0.1 to 4 ng/microL in urine with a signal-to-noise ratio of 10:1.

Adrenergic beta-Antagonists↗

Determination of four anabolic steroid metabolites by gas chromatography/mass spectrometry with negative ion chemical ionization and tandem mass spectrometry.

A gas chromatography/mass spectrometry method is described which uses negative ion chemical ionization and tandem mass spectrometry for the determination of anabolic steroid metabolites. Four anabolic steroid metabolites to be derivatized by Pentafluoropropionic anhydride (PFPA) were determined using gas chromatography/mass spectrometry (GC/MS) with negative chemical ionization (NCI) and NCI/MS/MS. The repeatability and reproducibility of this procedure were in the range of 5.3-9.7% and 6.1-10.2%, respectively. This method of derivatization with PFPA for NCI and NCI/MS/MS was useful to determine four metabolites of nandrolone, dromostanolone, methenolone and boldenone. The derivatized metabolites of boldenone could be detected to 2 ppb and the other three steroids could be detected to 25 ppb in urine at a signal-to-noise ratio of S/N = 3.

Anabolic Agents↗

Cyanide binding and active site structure in heme-copper oxidases: normal coordinate analysis of iron-cyanide vibrations of a3(2+)CN- complexes of cytochromes ba3 and aa3.

The cyanide isotope-sensitive low-frequency vibrations of ferrous cyano complexes of cytochrome a3 are studied for cytochrome ba3 from Thermus thermophilus and cytochrome aa3 from bovine heart. Cyanide complexes of ba3 display three isotope sensitive frequencies at 512, 485, and 473 cm-1. The first is primarily an Fe-C stretching motion, whereas the lower wavenumber modes are bending motions. These iron-cyanide vibrations are independent of the redox levels of the other metal centers in the protein. On the other hand, the fully reduced bovine derivative complexed with cyanide gives rise to a bending vibration at 503 cm-1 and a stretching vibration at 469 cm-1. That is, the ordering of the stretching and bending frequencies is reversed from that of the bacterial protein. These results are analyzed by normal coordinate calculations to obtain comparative models for the binuclear O2 reducing site of the two proteins. We find that the observed frequencies are consistent with a linear Fe-C-N group and larger Fe-C stretching force constant (2.558 mdyn/A) for ba3 and a slightly bent Fe-C-N group (angle approximately 170 degrees) and a smaller Fe-C stretching force constant (2.335 mdyn/A) for aa3. Thus, there are significant differences in the interaction of cyanide with ferrous a3 in the two proteins that are most likely caused by a weaker proximal histidine interaction and stronger peripheral heme electron withdrawing effects in ba3. Possible sources of these protein-induced effects are discussed. Using the analysis developed here, comparison of the FeCN stretching and bending frequencies of the ferrous bovine a3-CN complex to those obtained from the ferric a3-CN complex suggests that upon conversion of the resting to the fully reduced protein, a conformational change occurs that constrains the ligand binding site.

Animals↗

Anthracene-1,4,9,10-tetraone derivatives: synthesis and antitumor activity.

A series of 2-alkylated anthracene-1,4,9,10-tetraone (ATO) derivatives were synthesized, and their antitumor action in ICR mice bearing S-180 cells and antiproliferative activity against L1210 cells were evaluated. Overall, the introduction of an alkyl group (C1-C8) at C-2 enhanced the antiproliferative activity. Among 2-(1-hydroxyalkyl)- or 2-(1-acetoxyalkyl)-ATO derivatives, four compounds possessing alkyl chain of an intermediate size (C4-C6) gave T/C values of > 300%. Acetylation at 1'-OH failed to cause an enhancement in the antitumor action, in contrast to a remarkable increase in antiproliferative activity. Although there was no direct relationship between antiproliferative activity and antitumor action, the compounds with lower antiproliferative activity tended to show higher antitumor activity. Further study shows that the antiproliferative activity of ATO derivatives may be explained properly neither by redox cycling nor arylating capacity.

Animals↗

Solid-state NMR studies of the membrane-bound closed state of the colicin E1 channel domain in lipid bilayers.

The colicin E1 channel polypeptide was shown to be organized anisotropically in membranes by solid-state NMR analysis of samples of uniformly 15N-labeled protein in oriented planar phospholipid bilayers. The 190 residue C-terminal colicin E1 channel domain is the largest polypeptide to have been characterized by 15N solid-state NMR spectroscopy in oriented membrane bilayers. The 15N-NMR spectra of the colicin E1 show that: (1) the structure and dynamics are independent of anionic lipid content in both oriented and unoriented samples; (2) assuming the secondary structure of the polypeptide is helical, there are both trans-membrane and in-plane helical segments; (3) trans-membrane helices account for approximately 20-25% of the channel polypeptide, which is equivalent to 38-48 residues of the 190-residue polypeptide. The results of the two-dimensional PISEMA spectrum are interpreted in terms of a single trans-membrane helical hairpin inserted into the bilayer from each channel molecule. These data are also consistent with this helical hairpin being derived from the 38-residue hydrophobic segment near the C-terminus of the colicin E1 channel polypeptide.

Amino Acid Sequence↗

Cytotoxic constituents of Saussurea lappa.

The crude extract of Saussurea lappa displayed significant lethality to brine shrimp larvae. Investigation of the causative components by bioactivity-directed fractionation resulted in the isolation of three C17-polyene alcohols. Based on various nmr spectral data, these compounds were identified as shikokiols which had been previously isolated from Cirsium nipponicum and/or Centaurea aegyptica. These C17-polyene alcohols exhibited moderate cytotoxicities against the human tumor cell lines, A549, SK-OV-3, SK-MEL-2, XF498, and HCT15.

Animals↗

2-(1-Oxyalkyl)-1,4-dioxy-9,10-anthraquinones: synthesis and evaluation of antitumor activity.

Fourty eight derivatives of 2-(1-oxyalkyl)-1,4-dioxy-9,10-anthraquinone were synthesized, and their antitumor activity was evaluated. On the whole, 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones (DHAQ = 1,4-dihydroxy-9,10-anthraquinone) showed stronger cytotoxic activity against L1210 cells than 2-(1-hydroxyalkyl)-1,4-dimethoxy-9,10-anthraquinones(DMAQ = 1,4-dimethoxy-9,10-anthraquinone), implying that free hydroxy groups at C-1 and C-4 of the anthraquinone structure are necessary for the cytotoxic activity. The bioactivity of 2-(1-hydroxyalkyl)-DHAQ derivatives differed according to the size of alkyl group at C-1; while the elongation of alkyl group over 7 carbon atoms failed to enhance the bioactivity, the derivatives possessing alkyl moiety of 1-6 carbon atoms showed an increase in the cytotoxicity and the antitumor activity in Sarcoma-180; 2-hydroxymethyl-DHAQ (ED50, 15 micrograms/ml; T/C, 125%), 2-(1-hydroxyethyl)-DHAQ(1.9 micrograms/ml; 139.2%), 2-(1-hydroxypropyl)-DHAQ (7.2 micrograms/ml; 135.1%), 2-(1-hydroxybutyl)-DHAQ (10.2 micrograms/ml; 125.3%), 2-(1-hydroxypentyl)-DHAQ (23.7 micrograms/ml; 110.1%), and 2-(1-hydroxyhexyl)-DHAQ (58 micrograms/ml; 108%). Next, 2-(1-Hydroxyalkyl)-DHAQ derivatives were acetylated to produce 2-(1-acetoxyalkyl)-DHAQ analogues. Although the acetylation somewhat enhanced the cytotoxicity, but not the antitumor action. In addition, the presence of phenyl group at C-1' enhanced the cytotoxicity and the T/C value, compared to alkyl groups of same size; 2-(1-hydroxy-1-phenyl)-DHAQ (ED50, 5.6 micrograms/ml; T/C, 137%).

Acetylation↗

Combinatorial control of Drosophila mef2 gene expression in cardiac and somatic muscle cell lineages.

The Drosophila mef2 gene encodes a MADS domain transcription factor required for the differentiation of cardiac, somatic, and visceral muscles during embryogenesis and the patterning of adult indirect flight muscles assembled during metamorphosis. A prerequisite for D-MEF2 function in myogenesis is its precise expression in multiple cell types during development. Novel enhancers for D-mef2 transcription in cardiac and adult muscle precursor cells have been identified and their regulation by the Tinman and Twist myogenic factors have been demonstrated. However, these results suggested the existence of additional regulators and provided limited information on the specification of progenitor cells for different muscle lineages. We have further characterized the heart enhancer and show it is part of a complex regulatory region controlling the activation and repression of D-mef2 transcription in several cell types. The mutation of a GATA sequence in the enhancer changes its specificity from cardial to pericardial cells. Also, the addition of flanking sequences to the heart enhancer results in expression in a new cell type, that being the founder cells of a subset of body wall muscles. As tinman function is required for D-mef2 expression in both the cardial and founder cells, these results define a shared regulatory DNA that functions in distinct lineages due to the combinatorial activity of Tinman and other factors that work through adjacent sequences. The analysis of D-mef2-lacZ fusion genes in mutant embryos revealed that the specification of the muscle precursor cells involved the wingless gene and the activation of a receptor tyrosine kinase signaling pathway.

Animals↗

Mechanisms of symptom in Bartoszyński's virus model.

This paper is concerned with Bartoszyński's process for rabies viruses introduced by Bartoszyński [R. Bartoszyński, A model for risk rabies, ISI invited paper No. 9, ISI 1-9, IX Warsaw, 1975, pp. 545-552; Math. Biosci. 24 (1975) 355; W. Klonecki (Ed.) Proceedings of the IASPS Symposium to honour Jerzy Neyman, Warsaw, 1976, pp. 19-28]. Our main interests are in developing mechanisms of a symptom--how the probability of the occurrence of the symptom is related to the process. Four mechanisms are suggested based on various biological backgrounds. The main variable of interests is the survival time--the time elapsing between initial infection and the occurrence of the symptom. Analytical results about the survival functions induced from the four suggested mechanisms are studied.

Animals↗

Edge detection in prostatic ultrasound images using integrated edge maps.

OBJECTIVE: We investigated an algorithm to detect grey level transitions with multiple scales of resolution to improve edge detection and localisation in ultrasound images of the prostate. INTRODUCTION: We had developed a non-analytical operator for prostate contour determination implemented with minimum and maximum filters and locate edges. We implemented a technique for improved determination of boundary parts in prostatic ultrasound images by adjusting the edge detection parameter to signal information. METHODS: First the influence of prefilter settings and edge detection parameters is investigated in a test image and a real ultrasound image. Then, local standard deviation is used to identify or fewer homogeneous regions that are filtered with course resolution, while areas with larger deviation that grey level transitions occur, which should be preserved using smaller filter sizes to improve edge localisation. RESULTS: Analysis of images with different filter sizes indicated that areas are merged for increasing filter sizes: less pronounced edges disappear or displace for larger filters. Two scales of resolution lead to an improved localisation of edges when smaller filter sizes are used in areas with an increased local standard deviation. CONCLUSIONS: This paper illustrates an edge detection method suitable as pre-processing step in interpretation of medical images. By adapting input parameters to signal information, object recognition can be applied in images from different imaging modalities. Also, disadvantages are discussed, resulting in a new application combining a localisation algorithm to find the initial contour and a delineation algorithm to improve the outlining of the resulting contour.

Algorithms↗

Expression of cyclin D1 in mouse B cell lymphomas of different histologic types and differentiation stages.

The G1 cyclin, cyclin D1, has been implicated in the development of human and mouse tumors. Here we describe immunohistochemical analyses of cyclin D1 for a large panel of mouse B cell tumors. In addition, we characterize cyclin D1 expression in a series of cultured cell lines that represent transformed B cells at different stages of development. Immunohistochemical analysis showed that for low-grade lymphomas, cyclin D1 was expressed by 83% of centroblastic centrocytic (CBCC) and 14% of small lymphocytic lymphomas (SLL). For high-grade tumors, 28% of B lymphoblastic and 23% of centroblastic tumors expressed cyclin D1, while all immunoblastic lymphomas were negative. Studies of RNA and protein prepared from cultured B lineage tumors showed that cyclin D1 was expressed by all pre-B and most B cell tumors but not by cell lines representative of late B cell differentiation or by plasma cells. Expression of cyclin D1 in the lymphomas was not associated with alterations in the genomic structure of the Fis-1 (Bcl-1) common proviral integration site or cyclin D1 itself or with cell growth activity as assessed by expression of proliferating cell nuclear antigen (PCNA).

Animals↗

Vestibular schwannoma with repeated intratumoral hemorrhage.

A symptomatic hemorrhage from a vestibular schwannoma is extremely rare, despite its relatively high incidence in the cerebellopontine angle. Much more unusual are repeated intratumoral hemorrhages. The authors report on such a rare case of repeated intratumoral hemorrhage from a vestibular schwannoma, presenting with sudden exacerbation of headache, nausea and vomiting. This second hemorrhage was confirmed by CT scan on the day of the onset of symptomatic exacerbation, which was 9 days after the initial CT scan, showing an enlarged amount of blood within the tumor. The MRI scan confirmed this CT finding. After removal, the tumor proved to be a typical vestibular schwannoma of mixed Antoni types A and B. Thin-dilated vessels with hemorrhage and hemosiderin-laden macrophages were observed. The patient's postoperative course was uneventful. A total of 28 reported cases of a single intratumoral hemorrhage in vestibular schwannomas, and one reported case of repeated hemorrhage are reviewed.

Adult↗

Expression of mRNA for type IV collagen alpha1, alpha5 and alpha6 chains by cultured dermal fibroblasts from patients with X-linked Alport syndrome.

COL4A5 mutations causing X-linked Alport syndrome (XLAS) are frequently associated with absence of the alpha3, alpha4,alpha5 and alpha6 chains of type IV collagen from basement membranes and increased amounts of the alpha1(IV) and alpha2(IV) chains in glomerular basement membrane. Although many COL4A5 mutations have been described in XLAS, the mechanisms by which these mutations influence the basement membrane appearance of chains other than alpha5(IV) remain poorly understood. In this study, we used dermal fibroblasts from eight normal individuals and nine males with XLAS to test the hypotheses that COL4A5 mutations increase transcription of COL4A1 and suppress transcription of COL4A6. Ribonuclease protection assays revealed that alpha1(IV), alpha5(IV) and alpha6(IV) transcripts were expressed in cultures of dermal fibroblasts. The mRNA levels for alpha1(IV) in eight of nine patients with XLAS were not increased compared to controls; one patient with a large COL4A5 deletion showed significant elevation of alpha1(IV) mRNA levels. No differences in steady-state mRNA levels for alpha6(IV) were found when XLAS fibroblasts were compared with controls, even though little or no alpha6(IV) protein was detectable at the dermal-epidermal junction by immunofluorescence study. This finding suggests that post-transcriptional events account for the absence of alpha6(IV) in the Alport dermal-epidermal junction.

Adolescent↗

Applications of dendrimers in bio-organic chemistry.

Dendrimers represent a new class of highly branched polymers whose interior cavities and multiple peripheral groups facilitate potential applications in biomedicine and bio-organic chemistry. Major advances in the past year were made in the synthesis and study of new carbohydrate, nucleic acid, and peptide dendrimers, as well as in the use of dendrimers as magnetic resonance imaging contrast agents, as agents for cellular delivery of nucleic acids, and as scaffolds for biomimetic systems.

Biochemical Phenomena↗