Search PubMed⌕ Search

Biomedical subjects

S C Yan

Publications and source records attributed to S C Yan.

At least 19 recordsLinked to original sources

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Algorithms↗

Interaction of antimony tartrate with the tripeptide glutathione implication for its mode of action.

The tripeptide glutathione (gamma-L-Glu-L-Cys-Gly, GSH) is thought to play an important role in the biological processing of antimony drugs. We have studied the complexation of the antileishmanial drug potassium antimony(III) tartrate to GSH in both aqueous solution and intact red blood cells by NMR spectroscopy and electrospray ionization mass spectrometry. The deprotonated thiol group of the cysteine residue is shown to be the only binding site for Sb(III), and a complex with the stoichiometry [Sb(GS)3] is formed. The stability constant for [Sb(GS)3] was determined to be log K 25 (I = 0.1 M, 298 K) based on a competition reaction between tartrate and GSH at different pH* values. In spite of being highly thermodynamically stable, the complex is kinetically labile. The rate of exchange of GSH between its free and Sb-bound form is pH-dependent, ranging from slow exchange on the 1H-NMR timescale at low pH (2 s-1 at pH 3.2) to relatively rapid exchange at biological pH (> 440 s-1). Such facile exchange may be important in the transport of Sb(III) in various biofluids and tissues in vivo. Our spin-echo 1H-NMR data show that Sb(III) rapidly entered red blood cell walls and was complexed by intracellular glutathione.

Antimony Potassium Tartrate↗

Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 2. Sidechain optimization and demonstration of in vivo efficacy.

Potent, subnanomolar thrombin inhibitors 4, 5, and 6 are developed through side chain optimization of novel, benzo[b]thiophene-based small organic entities 2 and 3 and through SAR additivity studies of the new structural elements identified. X-ray crystallographic studies of 4b-thrombin complex revealed a hydrophobic and an electrostatic interaction of these new elements with thrombin at the S2 and S3 binding sites. In vitro and in vivo pharmacological studies showed that 4, 5, and 6 are potent anticoagulants in human plasma with demonstrated antithrombotic efficacy in a rat model of thrombosis.

Animals↗

66A-078:a kappa-opiate receptor agonist for amelioration of spinal spasticity.

The effect and mechanism of kappa opiate receptor agonist and high-frequency electrostimulation of acupoints in treating spinal spasticity were studied. The spinal spastic models were made by gradual mechanical compression on the cervical spinal cord of rabbits. 24 prepared rabbits were divided into 3 groups randomly, and each group with 8 rabbits was given intrathecally kappa-receptor agonist 66A-078, kappa-receptor antagonist +66A-078 and normal saline respectively. The degree of spasticity was quantified by both clinical score and electrophysiological examinations. The result showed that the spasticity was markedly inhibited by intrathecal injection of 66A-078 and that the kappa-receptor antagonist (naloxone) reversed this effect. We can infer that the antispastic effect of 66A-078 is mediated by kappa-receptors. This result is helpful in explaining the immediate antispastic mechanism of high-frequency electrostimulation of acupoints discussed in previous study.

Animals↗

Transcutaneous electrical nerve stimulation for treatment of spinal spasticity.

Thirty-two patients with spinally originated muscle spasticity were treated with a transcutaneous electrical nerve stimulator, the Han's acupoint nerve stimulator (HANS) via skin electrodes placed over the acupoints on the hand and leg. High frequency (100 Hz), but not the low frequency (2 Hz), stimulation was effective in ameliorating muscle spasticity. While the therapeutic effect lasted for only 10 minutes in the first treatment, it became consolidated after consecutive daily treatment for 3 months. The anti-spastic effect induced by high frequency electrical stimulation can be partially reversed by a high dose of naloxone. The results suggest that the anti-spastic effect elicited by peripheral electrical stimulation is mediated, at least in part, by the endogenous opioid ligand interacting with the kappa opiate receptors, most probably dynorphin, in the central nervous system.

Acupuncture Points↗

Recombinant human thrombomodulin. Regulation of cofactor activity and anticoagulant function by a glycosaminoglycan side chain.

Two glycoforms of a secretable human thrombomodulin mutant [TMD1-105 and TMD1-75; Parkinson, Grinnell, Moore, Hoskins, Vlahos & Bang (1990) J. Biol. Chem. 265, 12602-12610] were expressed in human 293 cells and used to study the role of glycosylation in the functions of this endothelial-cell thrombin receptor. Carbohydrate content analysis and intrinsic labelling with [3H]glucosamine and [35S]sulphate showed that TMD1-105 contained a chondroitin sulphate whereas TMD1-75 did not. Other than chondroitin sulphate, the carbohydrate contents of the two glycoforms were identical, indicating similar glycosylation patterns at other O-linked and N-linked sites in the two glycoforms. The properties of TMD1-105 were converted into those of TMD1-75 by chondroitin ABC lyase digestion. Trypsin digestion of labelled TMD1-105 permitted isolation of two overlapping peptides that contained chondroitin sulphate, spanned the entire O-glycosylation domain and had O-glycosylation sites at Ser-492, Ser-498, Thr-500, Thr-504 and Thr-506. The chondroitin sulphate-attachment site was assigned to Ser-492 as this residue is conserved in mouse and bovine thrombomodulin and lies within a sequence Ser-Gly-Ser-492-Gly-Glu-Pro, which has strong similarity to chondroitin sulphate attachment sites in other proteoglycans. Five peptides with N-linked carbohydrate were also isolated and contained glycosylation sites in the lectin-like domain (Asn-47, Asn-115, Asn-116) and in the fourth (Asn-382) and fifth (Asn-409) epidermal growth factor domains. The role of N-linked and simple O-linked carbohydrates in the functions of human thrombomodulin remain unclear. The present studies demonstrate, however, that the presence of chondroitin sulphate in human thrombomodulin has profound effects on all of the anticoagulant properties of this important anticoagulant thrombin receptor.

Amino Acid Sequence↗

Effect of low- and high-frequency TENS on Met-enkephalin-Arg-Phe and dynorphin A immunoreactivity in human lumbar CSF.

Transcutaneous nerve stimulation (TENS) treatment was given for 30 min to 37 patients divided into 3 groups of 10 patients and 1 group of 7 patients. Two groups received low-frequency (2 Hz) and the other 2 groups high-frequency (100 Hz) stimulation. A diagnostic lumbar cerebrospinal fluid (CSF) sample was obtained immediately before and after stimulation. The CSF samples were subjected to analysis of immunoreactive (ir) opioid peptides, Met-enkephalin-Arg-Phe (MEAP) from preproenkephalin and dynorphin A (Dyn A) from preprodynorphin, respectively. Low frequency TENS applied on the hand and the leg resulted in a marked increase (367%, P less than 0.05) of ir-MEAP but not ir-Dyn A, whereas high-frequency (100 Hz) TENS produced a 49% increase in ir-Dyn A (P less than 0.01) but not ir-MEAP. This is the first report in humans that 2 Hz and 100 Hz peripheral stimulation induces differential release of peptides from preproenkephalin and preprodynorphin, respectively.

Adult↗

[Effect of Polyporus umbellatus polysaccharide on function of macrophages in the peritoneal cavities of mice with liver lesions].

The cells in peritoneal cavities of mice were taken out and cultured in vitro. The amount to release H2O2 of the macrophages was assayed by fluorimetry. Polyporus umbellatus polysaccharide (PUP) could not only increase the number of macrophages and the amount of H2O2 release in the peritoneal cavities of normal mice, but also raise the lowered number of macrophages and the ability to release H2O2 in the peritoneal cavities of the mice with liver lesions caused by CCl4 significantly. So PUP could improve the cellular immunity of normal mice and the mice with liver lesions.

Animals↗

Characterization and novel purification of recombinant human protein C from three mammalian cell lines.

Human Protein C (HPC), an antithrombotic factor with potential clinical utility, is a vitamin K-dependent protein that has several complex post-translational modifications. In an effort to define the functional roles of these modifications, recombinant HPC (rHPC) was expressed in and characterized from 3 adenovirus-transformed cell lines. The rHPC in crude culture medium from the 3 cell lines displayed anticoagulant activities that were either higher, slightly lower or much lower than that of plasma HPC. The rHPC from each cell line was purified and characterized using a novel, but simple chromatographic method, termed "pseudo-affinity", capable of resolving molecules differing by only very slight modifications. We demonstrate the critical dependence of full gamma-carboxylation on the function of this protein. In addition, our data indicate that both the gamma-carboxyglutamate and glycosyl contents affect the functional activities of rHPC.

Adenoviruses, Human↗

Diagnosis and treatment of giant cell tumor in the thoracic spine.

A 23-year-old woman with incomplete paralysis was operated upon for a giant cell tumor in the thoracic spine. X-ray films revealed a destruction lesion in the vertebral body of the 12th thoracic vertebra. On the plain thoracic computed tomography scan, the finding was a soap-bubble appearance with a linear high density area in the mass lesion which destroyed the vertebral body. Preoperative angiography showed no apparent feeding artery to the tumor tissue; preoperative myelography showed incomplete block at the level of the 12th thoracic vertebra. A radical operation was carried out in one stage via a combined antero-posterior approach. In order to give radiotherapy immediately after operation, a vascular pedicled rib graft was made. This paper discusses the role of thoracic computed tomography scan in the diagnosis of giant cell tumor and the surgical techniques used in treatment.

Adult↗

Post-translational modifications of proteins: some problems left to solve.

Three major questions regarding the post-translational modification of amino acid side chains in proteins are briefly considered: (1) What are the biological functions of the reactions, (2) what is the specificity of the processing reactions in selecting only a few or sometimes even only one residue for modification, and (3) how do we solve the uniqueness of the processing steps in the production of recombinant proteins? The answers to these questions are not obvious at this time.

Protein Processing, Post-Translational↗

Preventing effect of "liuwei dihuang decoction" on esophageal carcinoma.

Liuwei Dihuang Decoction is a representative classic prescription for nourishing Yin in Traditional Chinese Medicine. Experimental and clinical studies showed that the recipe could 1. inhibit carcinogenesis of anterior stomach by N-nitrososarcosine ethyl ester in mice; 2. inhibit the formation of lung tumors induced by Urethan in mice; 3. decrease spontaneous tumorigenesis in LACA strain; 4. inhibit the mutagenic activity of Endoxan in micronuclear test. Patients with epithelial dysplasia of esophagus, a preneoplastic lesion, were treated by using this recipe. The canceration rate within 1 year was 2.2% in the treated and 12.4% in an untreated group. Within 5 years these rates were 9% and 26% respectively (p less than 0.025).

Animals↗