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C Yu

Publications and source records attributed to C Yu.

At least 361 records · Page 20Linked to original sources
PubMed1994

NMR and dynamical simulated annealing studies on the solution conformation of urotensin II.

We determined the structure in solution of the vaso-constrictor hormone urotensin II (dodecapeptide) using nuclear magnetic resonance spectroscopy. Complete assignment of all proton resonances has been achieved and the structural information has been obtained from the interproton distance measurements derived from the nuclear Overhauser enhancement data. A combination of distance geometry and dynamical simulated annealing techniques was used to calculate the structure in solution. Nine resultant structures with fewer distance constraint violations were selected that satisfy the experimental restraints very well. The conformation of the molecule in the cyclic hexapeptide segment (core region) is well-defined whereas the N-terminal segment is disordered. This result correlates very well with the earlier predictions about the biologically active and inactive roles played by the core and the N-terminal segment respectively.

Amino Acid Sequence↗
PubMed1994

Cardiotoxin III from the Taiwan cobra (Naja naja atra). Determination of structure in solution and comparison with short neurotoxins.

The structure in solution of cardiotoxin III, a membrane toxin purified from the venom of the Taiwan cobra, Naja naja atra, is reported. Sequence-specific assignment of 1H-NMR lines was completed and the NMR data show the presence of a triple and a double-stranded antiparallel beta-sheet. Many NOE cross peaks identified in NOESY spectra were applied as distance constraints based on a hybrid distance geometry/dynamical simulated annealing technique; 20 structures were found within a single family. The average value of atomic RMS differences between the 20 structures and their geometric mean is 0.087 nm for the backbone atoms and 0.152 nm for all heavy atoms; they are 0.055 nm and 0.12 nm, respectively for the segments of secondary structure. In these selected structures the backbone of the polypeptide chain folds such that five strands emerge from a globular head. Three major loops link these strands to form a double and a triple-stranded antiparallel beta-sheet. Comparison of the structures of the toxin in solution with the X-ray crystal structure of its homologous protein, cardiotoxin V4II from Naja mossambica mossambica, showed good agreement between the structures except at segments of the turns. As the functions of short neurotoxins and cardiotoxins are distinct, despite their similar secondary structural patterns and tertiary folding, a comparative analysis has been carried out between cardiotoxin III and short neurotoxins of known structures. We discuss their structural features in order to clarify relationships between their structure and function.

Amino Acid Sequence↗
PubMed1994

Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis.

OBJECTIVE: To quantify interleukin-1 receptor antagonist (IL-1ra) and IL-1 production and gene expression by rheumatoid arthritis (RA) synovial tissue (ST) cells. METHODS: IL-1 alpha, IL-1 beta, and IL-1ra protein levels were measured by enzyme-linked immunosorbent assay in fresh and cultured ST cells, purified synovial macrophages, and fibroblast-like synoviocytes (FLS). The relative expression of the secreted form of IL-1ra (sIL-1ra) and the alternatively spliced intracellular form (icIL-1ra) was determined by reverse transcription polymerase chain reaction (RT-PCR) techniques. RESULTS: IL-1 alpha, IL-1 beta, and IL-1ra were present in fresh and cultured ST cell samples of synovium from RA and osteoarthritis patients. IL-1ra:IL-1 ratios ranged from 1.2 to 3.6, which is below the 10-100-fold excess of IL-1ra needed to inhibit IL-1 bioactivity. Isolated CD14+ synovial macrophages secreted IL-1ra, but the amount was much less than that of alveolar or in vitro-derived macrophages. Cultured FLS contained intracellular IL-1ra but secreted little IL-1ra into the culture supernatants. RT-PCR showed that icIL-1ra mRNA was more abundant than sIL-1ra mRNA in FLS and unfractionated ST cells. CONCLUSION: IL-1ra production by RA ST cells is deficient relative to total production of IL-1.

Arthritis, Rheumatoid↗
PubMed1994

An algorithm and computer program for calculating the mean transit time and distribution rate parameters of generated metabolites undergoing linear tissue distribution and linear or non-linear central elimination.

A method is described for calculating the mean transit time and distribution rate parameters of a generated primary metabolite undergoing linear distribution and linear or non-linear central elimination, and of catenary metabolites with any precursor order. It is also applicable to a drug and its interconversion metabolite and does not require separate administration of the metabolite. The method allows steady-state volume of distribution and distribution clearance of a metabolite to be calculated, provided that the central volume of distribution of the metabolite is known. An algorithm and computer program to implement the proposed method are presented. The calculations require the plasma concentration versus time curves of the metabolite and its precursor. The method is applied to both published and simulated data.

Algorithms↗
PubMed1994

Understanding patterns of immunoglobulin gene rearrangements.

When immunoglobulin (Ig) gene rearrangements are analyzed, several patterns emerge. The rearrangements at the various loci generally appear in a specific temporal order. In addition, within a given locus the frequency of rearrangement of the various gene segments is not equal but is skewed towards preferential rearrangement of particular gene segments. Understanding the reasons for these patterns will shed light on the mechanism of recombination, the regulation of rearrangement, and the relationship between Ig gene rearrangement and B cell development. In this review, we discuss evidence that the observed patterns of Ig gene rearrangement are due to a combination of factors including the recombination signal sequences, sequences in the coding termini, the accessibility of genetic elements to V(D)J recombinase, and cellular selection.

Animals↗
PubMed1994

Antineoplastic activity of benzimidazo[1,2-b]-isoquinolines, indolo[2,3-b]quinolines, and pyridocarbazoles.

Substituted pyrido[3,4-b]carbazoles, pyrido[2,3-b]carbazoles, indolo[2,3-b]quinolines, and benzimidazo[1,2-b]-isoquinolines were synthesized and evaluated for biological activity. Several methylated derivatives of these heterocyclic compounds had similar activity to ellipticine as mammalian topoisomerase II inhibitors. Methylated derivatives of these heterocyclic compounds were also highly active in vitro, inhibiting the growth of several human tumor cell lines. These data demonstrate that the antineoplastic activity associated with ellipticine can be retained within a wide variety of analogous heterocyclics.

Animals↗
PubMed1994

NMR spectra and restrained molecular dynamics of the mushroom toxin viroisin.

The conformation of viroisin, the monocyclic toxic heptapeptide of the virotoxin family from mushroom Amanita virosa, was analysed using two-dimensional nuclear magnetic resonance spectroscopy and restrained molecular dynamics simulations. All proton signals were completely assigned, and interproton distances were determined using data from rotating-frame nuclear Overhauser enhancement. The backbone dihedral angles were deduced from measurements of coupling constants. The temperature dependence of the amide proton chemical shifts provided information about hydrogen bonding. Six probable solution conformations of viroisin were derived from the use of distance geometry and restrained molecular dynamics based on a set of distance constraints obtained from experimental data. The results of the structural analysis indicate that viroisin has a well ordered conformation in solution. In all these conformations the functional groups essential for toxicity orient themselves in the same direction so as to bind to the target proteins. This feature is consistent with previous results about the formation of a hydrophobic pocket on one side of the molecule.

Amanitins↗
PubMed1994

In search of the real respiratory neurons: culture of medullary fetal cells sensitive to CO2 and low pH.

Although extensively pursued, the real respiratory neurons have remained elusive. We departed from the more conventional physiologic and morphologic methods of system and tissue examination and cultured dissociated fetal rat cells from the areas of the nucleus ambiguus and the nucleus tractus solitarius located within the 2 mm rostral to the obex. Pacemaker-like cells, with a regular single or bursting activity, studied at 3-5 weeks of age, responded to very small pulses of CO2 (50 ms) and low pH with an increase in spike frequency and a decrease in amplitude. Other irregularly beating or silent cells did not respond or else required very large pulses (> 200 ms) to do so. The pacemaker cells also responded to hypoxia induced by administration of sodium hydrosulfite with an increase in spike frequency and amplitude; high oxygen (> 600 Torr) and adenosine produced a decrease in electrical activity. Most of these cells were multipolar after staining with antibodies to neuron-specific enolase and fragment C of tetanus toxin. They did not stain for choline acetyltransferase. The results suggest that these cultured cells, expressing a phenotype inherently responsive to CO2 and low pH, have the characteristics of central respiratory chemoreceptors, and may be involved in the generation of the respiratory rhythm.

Animals↗
PubMed1994

Characteristics of acupuncture meridians and acupoints in animals.

In recent years, an increasing number of studies has been conducted on the biophysical characteristics of the meridians and acupoints in humans and animals. The authors aim to further illustrate the objective existence and superficial locations of the meridians in various species of animals. Twelve sheep, ten goats, thirteen pigs, eleven cats, eight rabbits and seven donkeys were used to measure low impedance lines (LILs) and high percussion sound lines (HPSLs) on the skin surface of the animals, along the vertical planes of the dorsal line, using electrical impulses and high percussion sound. The results of these studies are given.

Acupuncture Points↗
PubMed1994

Solution conformation of enopeptin A, a depsipeptide antibiotic, using 2D NMR and restrained molecular dynamics studies.

Studies on the solution conformation of the cyclic depsipeptide antibiotic enopeptin A have been carried out using 2D NMR and molecular modelling techniques. The proton resonances of the antibiotic in DMSO-d6 have been assigned by the use of TOCSY and ROESY experiments. The interproton distance information obtained from the ROESY experiments have been used as the basis for elucidating the probable structures in solution. The restrained molecular dynamics technique was applied to calculate the structures in solution, and six resultant structures with fewer distance constraint violations were obtained that satisfy the experimental restraints very well. The conformation of the cyclic moiety of the molecules is well defined whereas the aliphatic chain segment is disordered.

Amino Acid Sequence↗
PubMed1994

[Studies on the detection of Legionella pneumophila by the application of polymerase chain reaction (PCR)].

DNA fragment of Legionella pneumophila, the PCR was performed with a pair of artificial synthesized primer. Results of agarose electrophoresis and EB staining showed that there was a 870 bp band shared by serogroups 1-14 of L.pneumophila. The sensitivity of PCR in detecting Legionella from water was 350cfu/ml, however, the specific DNA probe labeled with 32P was .43cfu/ml by blot hybridization. The positive rate of tissue specimens from infected guinea-pigs with Legionella pneumophila was 83.3% by PCR detection, and only 26.6% by bacteriological culture method. An outbeak caused by Lp10 was verified by PCR. The result showed that the PCR could detect the infection of Legionella rapidly, specifically and sensitively.

Animals↗
PubMed1994

[Cigarette smoking and circulatory crisis in tissue transfer].

Circulatory crisis occurred in 2 cases of toe-to-hand transfer and 1 case of musculocutaneous free flap after smoking. Two of them failed and 1 survived after exceeding anti-spasm and anti-thrombosis treatment. Experimental studies showed harmful influences of cigarette smoking on endothelial healing process at the vascular anastomosis site, which was covered by endothelial cells in 16%-32% and platelet in 8%-10% of the smoking group 5-10 days after operation, but in 75%-100% and 0% of the normal group. The mechanism and characteristics of circulatory crisis caused by cigarette smoking are discussed.

Adult↗
PubMed1993

Design of antineoplastic agents on the basis of the "2-phenylnaphthalene-type" structural pattern. 2. Synthesis and biological activity studies of benzo]b]naphtho[2,3-d]furan-6,11-dione derivatives.

Based on the "2-phenylnaphthalene-type" structural pattern hypothesis developed in our laboratory, a number of benzo[b]naphtho[2,3-d]furan-6,11-diones were designed, synthesized, and evaluated in vitro for their inhibitory action against the growth of human promyelocytic leukemia cells (HL-60), small-cell lung cancer (SCLC), SCLC cells resistant to cisplatin (SCLC/CDDP), National Cancer Institute's disease-oriented primary antitumor 60 cell-line panel, and drug-stimulated topoisomerase II-mediated DNA cleavages. Many compounds designed were found to possess potent activity in one or more of the biological tests. In general, activity found in one of the cell lines tested is often echoed in other cell lines and many also expressed substantial inhibitory activity against topoisomerase II-mediated cleavage activities. One of these compounds, 3-[2-(dimethylamino)ethoxy]-1-hydroxybenzo[b]naphthol[2,3-d]furan- 6,11-dione (8j), exhibited strong inhibitory activity throughout the entire series of test panel. Thus, it appears that the proposed structural pattern hypothesis has received substantial support through experimental verification.

Antineoplastic Agents↗
PubMed1993

DNA minor groove-binding ligands: a different class of mammalian DNA topoisomerase I inhibitors.

A number of DNA minor groove-binding ligands (MGBLs) are known to exhibit antitumor and antimicrobial activities. We show that DNA topoisomerase (Topo) I may be a pharmacological target of MGBLs. In the presence of calf thymus Topo I, MGBLs induced limited but highly specific single-strand DNA breaks. The 3' ends of the broken DNA strands are covalently linked to Topo I polypeptides. Protein-linked DNA breaks are readily reversed by a brief heating to 65 degrees C or the addition of 0.5 M NaCl. These results suggest that MGBLs, like camptothecin, abort Topo I reactions by trapping reversible cleavable complexes. The sites of cleavage induced by MGBLs are distinctly different from those induced by camptothecin. Two of the major cleavage sites have been sequenced and shown to be highly A + T-rich, suggesting the possible involvement of a Topo I-drug-DNA ternary complex at the sites of cleavage. Different MGBLs also exhibit varying efficiency in inducing Topo I-cleavable complexes, and the order of efficiency is as follows: Hoechst 33342 and 33258 >> distamycin A > berenil > netropsin. The lack of correlation between DNA binding and cleavage efficiency suggest that, in addition to binding to the minor grooves of DNA, MGBLs must also interact with Topo I in trapping Topo I-cleavable complexes.

Animals↗
PubMed1993

Chemotaxis of the marine bacterium Vibrio furnissii to sugars. A potential mechanism for initiating the chitin catabolic cascade.

Immense quantities of chitin are catabolized by marine bacteria, and this process involves at least three signal transduction systems in Vibrio furnissii. One system, chemotaxis to chitin oligosaccharides, is probably used to colonize chitin particles. But how do the first few cells find this highly insoluble polysaccharide? The following hypothesis is proposed to answer this question: the bacteria respond to soluble chemo-attractants in exudates from injured organisms. Virtually all chitin-producing organisms also contain glucose and/or trehalose, often at high concentrations such as trehalose in insect hemolymph. Chemotaxis of V. furnissii was therefore studied with a variety of sugars. Fructose, ribose, and glycerol are catabolites but not attractants. The cells exhibit weak constitutive taxis to Glc and GlcNAc. After induction, they show a weak response to galactose but are strongly attracted to the following substrates of the phosphoenolpyruvate:glycose phosphotransferase system (PTS): GlcNAc, trehalose, glucose, sucrose, mannose, and mannitol. There is a rough qualitative but no quantitative correlation between the rate of phosphorylation and the chemotactic response to PTS sugars. Trehalose is especially noteworthy because it is phosphorylated at a very rapid rate by uninduced cells but is not an attractant until the cells are induced. We suggest that unidentified inducible factors link the PTS to chemotaxis.

Carbohydrate Metabolism↗