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Biomedical subjects

Y C Shen

Publications and source records attributed to Y C Shen.

At least 19 recordsLinked to original sources

The use of Fourier-transform infrared spectroscopy for the quantitative determination of glucose concentration in whole blood.

Fourier-transform infrared transmission spectroscopy has been used for the determination of glucose concentration in whole blood samples from 28 patients. A 4-vector partial least-squares calibration model, using the spectral range 950-1200 cm(-1), yielded a standard-error-of-prediction of 0.59 mM for an independent test set. For blood samples from a single patient, we found that the glucose concentration was proportional to the difference between the values of the second derivative spectrum at 1082 cm(-1) and 1093 cm(-1). This indicates that spectroscopy at these two specific wavenumbers alone could be used to determine the glucose concentration in blood plasma samples from a single patient, with a prediction error of 0.95 mM.

Blood Glucose↗

Stability of exploratory eye movements as a marker of schizophrenia--a WHO multi-center study. World Health Organization.

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Adult↗

Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice.

BACKGROUND: Tissue factor initiates blood coagulation after atherosclerotic plaque disruption. Tissue factor pathway inhibitor (TFPI) inhibits tissue factor activity and may reduce thrombus formation in this setting. We evaluated the effect of heterozygous TFPI deficiency on the development of atherosclerosis and thrombosis in atherosclerosis-prone mice. METHODS AND RESULTS: Mice with a combined heterozygous TFPI deficiency and homozygous apolipoprotein E deficiency (TFPI(+/-)/apoE(-/-)) were generated by crossbreeding, and they were analyzed for atherosclerosis throughout the vascular tree. Compared with mice with a normal TFPI genotype (TFPI(+/+)/apoE(-/-)), mice with a TFPI deficiency exhibited a greater atherosclerotic burden involving the carotid and common iliac arteries. Staining for active tissue factor within the plaque revealed more activity in TFPI(+/-)/apoE(-/-) mice compared with TFPI(+/+)/apoE(-/-) mice. Consistent with increased plaque tissue factor activity, the time to occlusive thrombosis after photochemical carotid plaque injury was significantly decreased in TFPI(+/-)/apoE(-/-) mice. CONCLUSIONS: These observations indicate that TFPI protects from atherosclerosis and is an important regulator of the thrombosis that occurs in the setting of atherosclerosis.

Animals↗

Analysis of a murine anti-ganglioside GD2 monoclonal antibody expressing both IgG2a and IgG3 isotypes: monoclonality, apoptosis triggering, and activation of cellular cytotoxicity on human melanoma cells.

In this study we have documented a hybridoma secreting an unusual MAb, which expresses both IgG3 and IgG2a subclasses with a lambda-light chain. How this dual expression of isotypes was exactly brought about is not clear. To resolve this problem, it will have to wait the complete sequence analysis the heavy chain gene of MAb 9C4. Although the expression of IgG2a was about 50% that of IgG3, antibody titration studies showed the major binding affinity of MAb 9C4 to GD3-positive cells being mostly contributed by the IgG3 rather than IgG2a part of the antibody. This antibody could induce apoptosis in melanoma cells in 10-15% of cells in vitro, but the generality of this phenomenon is yet to be confirmed by the use of different cell targets and different anti-GD2 MAbs other than 9C4. Aside from the demonstrated indirect killing mechanisms of many anti-GD2 MAbs through CDC and ADCC, MAb 9C4 induction of apoptosis represents an alternative mechanism of tumor cell killing, by which direct killing of anti-GD2 antibody takes its effect. This apoptotic effect was demonstrated for the first time with an anti-ganglioside monoclonal antibody. From the therapeutic point of view, the cytolytic activity of MAb 9C4-targeted ADCC/LAK killing against GD2-positive tumor cells to be more effective than that of LAK alone and a possibility for dendritic cells to effectively acquire antigen through pulsing with MAb-induced apoptotic cells are both of great clinical importance. Further studies are warranted aiming at elucidating the molecular basis of bi-isotypic specificity and aberrant isotype switching, molecular pathway of anti-GD2 antibody-induced apoptosis, and ways to improve clinical utility of this unusual hybridoma/MAb 9C4.

Animals↗

Two new polyhydroxysteroids from the gorgonian Isis hippuris.

Two new polyhydroxysteroids isihippurols A (1) and B (2) were isolated from the MeOH extract of the gorgonian Isis hippuris in addition to nine known steroids namely gorgosterol, 3alpha-acetoxy-24-methyl 11beta,18; 18,20beta; 22,25-triepoxy-5alpha-furostane, hippurin-1, 22-epi-hippuristanol, 22-epi-hippurin-1, 3-acetyl-2-deacetyl-22-epi-hippurin-1, 2-deacetylhippurin-1, 3beta, 7alpha, 11alpha-trihydroxygorgost-5-ene-12beta-acetate and 2-deacetyl-22-epi-hippurin-1. The structures of 1 and 2 have been determined as 1alpha, 3beta, 5alpha, 6beta, 11alpha-pentahydroxygorgosta-12beta-monoacetate and 1alpha, 3beta, 11alpha-trihydroxygorgosta-5alpha, 6alpha-epoxy-12beta-monoacetate respectively by spectral analysis and chemical correlation.

Animals↗

Three new furan derivatives and a new fatty acid from a Taiwanese marine sponge Plakortis simplex.

Three new furan derivatives, plakorsins A-C (6-8), together with a new fatty acid, plakortic acid (9), have been isolated from the Taiwanese marine sponge Plakortis simplex in addition to the known metabolites chondrillin (1), 6-epi-chondrillin (2), 2-oxo-2,5-dihydrofuran-5-acetic acid methyl ester (methyl 1,4-epoxy-1-oxo-2-hexenoate) (3), dimethyl beta-ketoadipate (4), and the monomethyl ester of cis,cis-muconic acid (5). The structures of these compounds were established mainly on the basis of spectral data and chemical methods. Biological studies revealed that compound 7 exhibited cytotoxic activity against COLO-250 and KB-16 cells, and compound 1 is active against KB-16 cells.

Animals↗

New sesquiterpene hydroquinones from a Taiwanese marine sponge, Hippospongia metachromia.

In addition to metachromins A (1), B (2), and E (9), two new sesquiterpene hydroquinones, hippochromins A and B (3, 4), were isolated from the Taiwanese marine sponge Hippospongia metachromia. The structures of 4--6 were established by extensive 2D NMR analysis. Metachromins A (1) and B (2), hippochromin A diacetate (5), and metachromin B monoacetate (8) exhibited potent cytotoxicities against human colon (COLO-205) and nasopharyngeal (KB) tumor cells, while compounds 6, 7, and 9 were inactive.

Animals↗

Taxane diterpenoids from the stem bark of Taxus mairei.

Three new 11(15-->1)-abeo-taxanes, taxumairols U-W (1-3), have been isolated from extracts of the stem bark of Formosan Taxus mairei. The structures of 1-3 were identified as 5alpha,7beta,9alpha,13alpha,20-pentaacetoxy-2alpha,10beta,15-trihydroxy-11(15-->1)-abeo-taxene, 5alpha,7beta,9alpha,20-tetraacetoxy-2alpha,10beta,13alpha,15-tetrahydroxy-11(15-->1)-abeo-taxene, and 2alpha,4alpha,7beta,10beta-tetraacetoxy-5beta,20-epoxy-9alpha,13alpha,15-trihydroxy-11(15-->1)-abeo-taxene, respectively, on the basis of 2D NMR techniques including COSY, HSQC, HMBC, and NOESY experiments as well as chemical reactions of compounds 1-3 to give 4 (5alpha,7beta,9alpha,10beta,13alpha,20-hexaacetoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene) and 5 (4alpha,7beta,10beta-triacetoxy-9alpha,13alpha-dibenzoxy-5beta,20-epoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene), which are also novel taxane derivatives. Taxumairols U (1) and V (2) exhibited significant cytotoxicities against human hepatoma tumor cells, while taxumairol W (3) was inactive.

Antineoplastic Agents, Phytogenic↗

Risperidone versus haloperidol in the treatment of acute exacerbations of chronic inpatients with schizophrenia: a randomized double-blind study.

The purpose of this study was to compare the efficacy and safety of risperidone and haloperidol in treatment-resistant chronic schizophrenic patients. Subjects (n = 78) who met DSM-III criteria for schizophrenia were randomly assigned to receive 6 mg/day of risperidone or 20 mg/day of haloperidol for 12 weeks. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS), and side-effects with the Treatment Emergent Symptom Scale (TESS). Risperidone produced a mean 39.8 +/- 24.1% reduction in total PANSS score compared to a mean 28.3 + 19.4% reduction in the haloperidol group (P < 0.05). Analysis of changes for the three subscores of the PANSS revealed that the general psychopathology and negative subscores were significantly improved in the risperidone group compared to the haloperidol group. As for the side-effects, the risperidone group showed a significantly lower TESS total score, as well as nervous system symptoms subscore and cardiovascular symptoms subscore, compared to the haloperidol group. Risperidone appears to be a more effective and better tolerated antipsychotic drug in treatment-refractory Chinese schizophrenia than haloperidol.

Adult↗

Pulmonary fibrosis is increased in mice carrying the factor V Leiden mutation following bleomycin injury.

Increased fibrin deposition following inflammatory lung injury has been proposed to facilitate the development of pulmonary fibrosis. Therefore, factors predisposing to thrombosis may affect the fibrotic response to injury. Activated protein C (aPC) resistance due to the factor V Leiden mutation (FvL) is a common genetic risk factor for vascular thrombosis. To examine the relationship between aPC resistance and the development of pulmonary fibrosis, lung inflammation was induced by bleomycin in mice carrying the FvL mutation. Three weeks following the instillation of 0.0375 U of bleomycin, the lungs of mice homozygous and heterozygous for FvL contained significantly more hydroxyproline (35 +/- 4 and 36 +/- 7 ug hydroxyproline/mg total protein, respectively) than wild-type mice (26 +/- 6 ug/mg protein, p <0.01 for both comparisons). These data demonstrate a strong relationship between aPC resistance and the pulmonary fibrosis that occurs following inflammatory lung injury.

Activated Protein C Resistance↗

Anti-inflammatory effects of the partially purified extract of radix Stephaniae tetrandrae: comparative studies of its active principles tetrandrine and fangchinoline on human polymorphonuclear leukocyte functions.

We hypothesized that prevention of neutrophil from activation may underlie the myocardial protective effect of the specially processed extract of radix Stephaniae tetrandrae (SPRST). Inflammatory responses in isolated peripheral human neutrophils were studied in the presence or absence of SPRST. SPRST (1-10 microg/ml) concentration-dependently prevented N-formyl-methionyl-leucyl-phenylalanine (fMLP)- or leukotriene B(4) (LTB(4))-induced neutrophil adhesion and transmigration. Comparable results were also observed in neutrophils pretreated with fangchinoline (Fan) or tetrandrine (Tet), two active components in SPRST. It has been reported that neutrophil adhesion/transmigration is mainly Mac-1 (CD11b/CD18)-dependent and could be modulated by reactive oxygen species (ROS) production. SPRST, Tet, and Fan diminished fMLP- or LTB4-induced Mac-1 up-regulation and ROS production. SPRST, Fan, Tet, and verapamil impaired fMLP-induced rapid intracellular alkalization, an essential mechanism for neutrophil ROS production, and [Ca(2+)](i) increment, suggesting that a calcium dependent pathway might be involved. Direct G protein activation by AlF(4)(-) also triggered [Ca(2+)](i) increment and adhesion that could be abolished by pertussis toxin and were partially reversed by SPRST, Fan, and Tet. These results reveal that inhibition of neutrophil adhesion and transmigration may account for SPRST's myocardial protective effect. This effect of SPRST may be mediated by component(s) in addition to Tet and Fan because combination of 0.1 microg/ml of Tet and Fan did not mimic the effect of SPRST. We conclude that SPRST exerts anti-inflammatory effects by interfering with ROS production and Ca(2+) influx through G protein modulation to prevent Mac-1 up-regulation in neutrophil activation.

Alkaloids↗

The L1-type cell adhesion molecule neuroglian influences the stability of neural ankyrin in the Drosophila embryo but not its axonal localization.

Ankyrins are linker proteins, which connect various membrane proteins, including members of the L1 family of neural cell adhesion molecules, with the submembranous actin-spectrin skeleton. Here we report the cloning and characterization of a second, novel Drosophila ankyrin gene (Dank2) that appears to be the result of a gene duplication event during arthropod evolution. The Drosophila L1-type protein neuroglian interacts with products from both Drosophila ankyrin genes. Whereas the previously described ankyrin gene is ubiquitously expressed during embryogenesis, the expression of Dank2 is restricted to the nervous system in the Drosophila embryo. The absence of neuroglian protein in a neuroglian null mutant line causes decreased levels of Dank2 protein in most neuronal cells. This suggests that neuroglian is important for the stability of Dank2 protein. However, neuroglian is not required for Dank2 axonal localization. In temperature-sensitive neuroglian mutants in which neuroglian protein is mislocated at the restrictive temperature to an intracellular location in the neuronal soma, Dank2 protein can still be detected along embryonic nerve tracts.

Amino Acid Sequence↗

Two new acetylenic derivatives and a new meroditerpenoid from a Taiwanese marine sponge Strongylophora durissima.

Further chemical examination of the sponge Strongylophora durissima yielded two new acetylenic derivatives, durissimols A (1) and B (2), and a new meroditerpenoid, strongylophorine-12 (5), in addition to the known acetylenic compounds, reneirin-2 (3), 18-hydroxyreneirin-2, melyne-C (4), duryne, siphanochalynol, and 24-ethylcholesterol (7). Among them, durissimol B (2) and duryne showed potent cytotoxicity against human gastric tumor (NUGC) cells.

Acetylene↗

New taxanes with an opened oxetane ring from the roots of Taxus mairei.

Two novel taxoids, taxumairols N (1) and O (2), have been isolated from extracts of the roots of Taxus mairei. The structures of 1 and 2 were identified as 7beta,9alpha,10beta,13alpha-tetraacetoxy-2alp ha, 4alpha,5alpha,20-tetrahydroxytax-11-ene and 7beta,9alpha,10beta, 13alpha-tetraacetoxy-1beta,2alpha,4alpha,5alp ha, 20-pentahydroxytax-11-ene on the basis of 1D and 2D NMR techniques including COSY, HMQC, HMBC, and NOESY experiments.

Magnetic Resonance Spectroscopy↗

Suppression of rat neutrophil reactive oxygen species production and adhesion by the diterpenoid lactone andrographolide.

The present study was to examine whether andrographolide, a diterpenoid lactone isolated from the anti-inflammatory herbal medicine Andrographis paniculata (Burm. f.) Nees. (Acanthaceae), has the ability to prevent phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS) production, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion by rat neutrophils. Results demonstrated that PMA (100 ng/ml) induced rapid accumulation of H2O2 and O2. in neutrophils within 30 minutes. Andrographolide (0.1 to 10 microM) pretreatment (10 min, 37 degrees C) significantly attenuated the accumulation of these two oxygen radical metabolites. Administration of andrographolide also significantly prevented fMLP-induced neutrophil adhesion. These data suggest that preventing ROS production and neutrophils adhesion may confer andrographolide the ability to be an anti-inflammatory drug.

Animals↗

Taxane diterpenoids from seeds of Taxus mairei.

A new 2(3-->20) abeotaxane, taxumairone A (1), and a new cis-p-coumaroyl myo-inositol have been isolated from the seeds of Taxus mairei in addition to taxin B (2), taxinine A, taxuspine X, decinnamoyltaxinine E, 5alpha-cinnamoyloxy-9alpha,10beta,13alpha- triacetoxy-taxa-4(20)11-diene and 5alpha-cinnamoyloxy-2alpha,9alpha,10beta,+ ++13alpha-tetraacetoxy-taxa-4(20)11-diene. The structure of 1 was determined by 2D-NMR spectral analysis and chemical correlation with taxin B (2). Compound 1 exhibited potent cytotoxicity against human colon carcinoma cells with an ED50 of 0.1 microg/ml.

Bridged-Ring Compounds↗

A novel cytotoxic C-methylated biflavone from the stem of Cephalotaxus wilsoniana.

Bioassay-directed fractionation of an ethanolic extract of Cephalotaxus wilsoniana has resulted in the isolation of a novel C-methylated biflavone, taiwanhomoflavone-A (1). Its structure was elucidated on the basis of spectroscopic analysis. Taiwanhomoflavone-A is cytotoxic with ED50 values of 3.4, 1.0, 2.0 and 2.5 microg/ml, respectively, against KB epidermoid carcinoma of nasopharynx, COLO-205 colon carcinoma, Hepa-3B hepatoma, and Hela cervix tumor cells.

Antineoplastic Agents, Phytogenic↗

Immunobiologic, cytogenetic and drug response features of a newly established cell line (SCRC-1) from renal small cell carcinoma.

PURPOSE: We describe the establishment and preliminary characterization of a cell line designated SCRC-1, which was derived from a primary renal small cell carcinoma. MATERIALS AND METHODS: Continuous cultures of a primary stage IVa renal small cell carcinoma and a xenograft in nude mice derived therefrom were characterized by immunohistology, electron microscopy, immunofluorescence/flow cytometry, cytogenetic analysis, and an in vitro drug resistance assay. RESULTS: SCRC-1 cells were reactive with antibodies to NSE, chromogranin-A, bombesin, Bcl-2, CD44s, CD44v6, CD44v7 to 8, vimentin and S100 protein (predominantly beta-subunit), and were unreactive with antibodies to EMA, CD54, EGFR(R1), URO-5, URO-7, URO-8 and URO-10. A similar immunoprofile was also found in both the primary tumor and the xenograft. Cytogenetic analysis revealed the following common clonal aberrations in all 50 metaphases analyzed: 45, XX, t (X;10;18) (p11;p11;q11), -der(18)t(X;10;18), indicating the clonal nature of this neoplasm. SCRC-1 cells showed low drug resistance to cyclophosphamide, doxorubicin, gemcitabine and fluorouracil, intermediate resistance to carmustine and mitomycin-C, and extreme resistance to cisplatin. CONCLUSION: We have documented the initial characterization of SCRC-1, which may be the first cell line reported to be derived from a primary small cell carcinoma of the kidney. This cell line can be used for further studies uncovering the biology and histogenesis of this rare cancer and delineating differences among small cell carcinomas of the kidney and other histological types.

Adult↗