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Biomedical subjects

L Z Sun

Publications and source records attributed to L Z Sun.

12 recordsLinked to original sources

Protein function classification via support vector machine approach.

Support vector machine (SVM) is introduced as a method for the classification of proteins into functionally distinguished classes. Studies are conducted on a number of protein classes including RNA-binding proteins; protein homodimers, proteins responsible for drug absorption, proteins involved in drug distribution and excretion, and drug metabolizing enzymes. Testing accuracy for the classification of these protein classes is found to be in the range of 84-96%. This suggests the usefulness of SVM in the classification of protein functional classes and its potential application in protein function prediction.

Amino Acid Sequence↗

ADME-AP: a database of ADME associated proteins.

Drug absorption, distribution, metabolism and excretion (ADME) often involve interaction of a drug with specific proteins. Knowledge about these ADME-associated proteins is important in facilitating the study of the molecular mechanism of disposition and individual response as well as therapeutic action of drugs. It is also useful in the development and testing of pharmacokinetics prediction tools. Several databases describing specific classes of ADME-associated proteins have appeared. A new database, ADME-associated proteins (ADME-AP), is introduced to provide comprehensive information about all classes of ADME-associated proteins described in the literature including physiological function of each protein, pharmacokinetic effect, ADME classification, direction and driving force of disposition, location and tissue distribution, substrates, synonyms, gene name and protein availability in other species. Cross-links to other databases are also provided to facilitate the access of information about the sequence, 3D structure, function, polymorphisms, genetic disorders, nomenclature, ligand binding properties and related literatures of each protein. ADME-AP currently contains entries for 321 proteins and 964 substrates.

Databases, Protein↗

Chiral derivatization reagents for drug enantioseparation by high-performance liquid chromatography based upon pre-column derivatization and formation of diastereomers: enantioselectivity and related structure.

Structures and related enantioselectivities of the respective chiral derivatization reagents (CDRs) for drug enantioseparation by high-performance chromatography based upon pre-column derivatization and diastereomeric formation are reviewed. The elution order of diastereomers caused reaction of some CDRs with enantiomeric amino acids and carboxylic acids. The development of new CDRs available for indirect HPLC methods is also discussed. (c) 2001 John Wiley & Sons, Ltd.

Chromatography, High Pressure Liquid↗

Exogenous melatonin: quantitative enhancement in vivo of cells mediating non-specific immunity.

Melatonin (MLT), a biogenic indoleamine and neuromodulator produced by the pineal gland, is known to activate T helper cells by means of direct binding to melatonin receptors on both Th1 and Th2 cells. The present in vivo study aimed to investigate the effect of exogenously administered MLT on the hemopoietic and immune cell populations of the bone marrow and spleen in healthy, young adult male mice at two distinct MLT exposure intervals. The neurohormone, administered daily through the diet (7-14 days), was homogenized into finely ground chow. Control mice received ground chow without MLT. The results revealed cell lineage-specific, quantitative, MLT exposure-time-dependent changes in both the bone marrow and spleen. NK cells and monocytes (both components of the non-specific immune system functioning as the first line of defense against neoplasia and virus infected cells) were significantly increased in the bone marrow by both 7 and 14 days of dietary melatonin. The quantitative increment in these two cell populations, in the organ of their production, i.e. the bone marrow, indicates that new cell proliferation/production may have been stimulated by MLT. In the spleen, as in the bone marrow, NK cell levels remained significantly elevated at both 7 and 14 days after melatonin exposure. However, the number of monocytes in the spleen did not maintain, at day 14 of MLT exposure, the high levels observed after 7 days of MLT, in spite of their sustained, high numbers at 14 days in the bone marrow. This suggests that the progeny of the apparently increased monocyte production in the bone marrow (elevated absolute numbers therein), had localized in anatomical sites (other than the spleen) also common to these cells. Thus, the selective, positive influences of in vivo administered, exogenous melatonin on cells mediating non-specific immunity suggests a plausible mechanism for numerous claims that it is responsible for tumor amelioration in patients.

Adjuvants, Immunologic↗

Growth hormone effects on essential amino acid absorption, muscle amino acid profile, N-retention and nutritional requirements of striped bass hybrids.

Improvements in modern commercial aquaculture are linked to the utilization of biotechnological methods and processes. The most visible approach has been the use of growth hormone (GH) and/or insulin-like growth factor I and II (IGF-I and II), to accelerate the growth of fish. Previously we have reported that the injection of bovine GH, (bGH) in striped bass hybrids increased the specific growth rate and food conversion efficiency without significant alteration of food consumption rate. In this paper we present the results of experiments in which growth, food consumption, conversion efficiency, ammonia excretion, and amino acid absorption were monitored for individual fish after bGH injection. The specific growth rate was stimulated by 50% without significant change in relative food consumption rate. Food conversion efficiency increased by 51%. Intestinal L-leucine absorption was increased by 25-40% at various concentrations tested. The relative N-retention was stimulated by 20% when computed raw. When a correction factor derived from the elevated amino acid absorption was introduced into the computations. the calculated relative N-retention was increased by 56%. Muscle amino acid profile was appreciably altered. We conclude GH supplementation or over-expression in aquaculture profoundly alters the physiological and nutritional conditions of fish. Nutritional profiles of fish food must be altered relative to these physiological changes in order to maximize growth.

Amino Acids↗

The American coneflower: a prophylactic role involving nonspecific immunity.

OBJECTIVE: In humans, considerable circumstantial evidence exists that indicates soluble root extracts of the American coneflower, genus Echinacea, may act to ameliorate virus-mediated afflictions, such as the common cold, influenza, and even AIDS and virus-based tumors. This study was designed to quantify, in normal mice, Echinacea-mediated, quantitative, dynamic changes, with time on both mature and precursor cells, of all the hemopoietic and immune-cell lineages in the spleen and bone marrow. DESIGN: A specific, commercially prepared potent extract of Echinacea root was provided daily in the diet for either 1 week or 2 weeks with the aim of establishing a possible mechanism of action for this herb. RESULTS: The data revealed that natural-killer (NK) cells and monocytes, both mediators of nonspecific immunity and well-demonstrated killers of virus-containing cells, were numerically and significantly increased in both the bone marrow and the spleen as early as 1 week after beginning treatment with the dietary herb. In contrast to our observations with NK cells and monocytes, the sizes of all other hemopoietic and immune cell populations in these two organs remained at control levels even after 2 weeks of daily dietary Echinacea. CONCLUSIONS: The work has demonstrated the specific nature of Echinacea-derived phytochemicals in acting as stimulants of those cells responsible for nonspecific immunity, as the first line of defense against virus-infected/transformed cells. The observations that these cells were elevated in the bone marrow indicates that at least one mechanism of action of this herb, is to stimulate new cell production in situ. The significant elevation of these two fundamental immune-cell populations, in normal animals, suggests a prophylactic role for this herb.

Animals↗

Induction of transforming growth factor-beta receptor type II expression in estrogen receptor-positive breast cancer cells through SP1 activation by 5-aza-2'-deoxycytidine.

Previous studies suggest that estrogen receptor-positive (ER+) breast cancer cells acquire resistance to transforming growth factor-beta (TGF-beta) because of reduced expression levels of TGF-beta receptor type II (RII). We now report that treatment of ER+ breast cancer cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-2'-dC) leads to accumulation of RII transcript and protein in three different cell lines. RII induction restored TGF-beta response in MCF-7L breast cancer cells as indicated by the enhanced activity of a TGF-beta responsive promoter-reporter construct (p3TP-Lux). A transiently transfected RII promoter-reporter element (RII-chloramphenicol acetyltransferase) showed an increase in activity in the 5-aza-2'-dC-treated MCF-7L cells compared with untreated cells, suggesting the activation of a transactivator of RII transcription. Using electrophoretic mobility shift assays, the enhanced binding of proteins from 5-aza-2'-dC-treated MCF-7L nuclear extracts to radiolabeled Sp1 oligonucleotides was demonstrated. An RII promoter-chloramphenicol acetyltransferase construct containing a mutation in the Sp1 site was not expressed in the 5-aza-2'-dC-treated MCF-7L cells, further demonstrating that induction of Sp1 activity by 5-aza-2'-dC in the MCF-7L cells was critical to RII expression. Northern analysis indicated that 5-aza-2'-dC treatment did not affect the Sp1 transcript levels. Western blot analysis revealed an increase of Sp1 protein in the 5-aza-2'-dC-treated MCF-7L cells, but there was no change in the c-Jun levels. Studies after cyclohexamide treatment suggested an increase in the Sp1 protein stability from the 5-aza-2'-dC-treated MCF-7L extracts compared with untreated control extracts. These results indicate that the transcriptional repression of RII in the ER+ breast cancer cells is caused by suboptimal activity of Sp1, whereas treatment with 5-aza-2'-dC stabilizes the protein thus increasing steady-state Sp1 levels and thereby leads to enhanced RII transcription and subsequent restoration of TGF-beta sensitivity.

Activin Receptors, Type I↗

Isolation and characterization of a spontaneously transformed malignant mouse mammary epithelial cell line in culture.

A method is described that permits the selection of spontaneously transformed mammary epithelial colonies from an untransformed mouse mammary epithelial cell line, NMuMG, and utilizes a long-term anchorage-independent growth of the transformants on soft agarose. These transformed cells (NMuMG-ST) are shown to be distinguishable from the untransformed cells by morphology, growth characteristics, induced carcinomas when transplanted into nude mice and ability to metastasize. This transformed phenotype displayed focal, multilayer growth and higher saturation density in comparison with the untransformed phenotype. Transplanted tumors as well as metastatic lung tumors in nude mice were adenocarcinomas morphologically similar to typical mammary tumors in humans. This selection procedure of mutant mammary cells from an immortalized cell line derived from normal mammary glands could be very useful to identify the genomic biomarkers in the growth regulation and malignant progression of breast cancer.

Animals↗

Growth factor balance and tumor progression.

The role of balance of negative and positive autocrine growth factors in malignant progression is reviewed with an emphasis on transforming growth factor alpha (TGF-alpha) as a stimulating factor and transforming growth factor beta (TGF-beta) as an inhibiting factor. Evidence suggests that in normal cells TGF-alpha is down regulated in non-dividing or quiescent states in vitro. Tumor cells which have early stage characteristics as represented by poor clonal growth and poor tumorigenicity in athymic mice also show repression of TGF-alpha in non-dividing states. Progression of this phenotype is induced by uncontrolled low level expression of TGF-alpha by transfection with a constitutive expression vector for the polypeptide. Transfection of the unprogressed phenotype with a constitutive anti-sense vector for TGF-beta, also leads to tumor progression by repressing the autocrine negative TGF-beta activity normally expressed by these cells. Both the upregulation of TGF-alpha and the repression of TGF-beta generated in vivo progression without changing growth rates in vitro. Instead, clonality and ability to reenter the cell cycle from quiescence were increased. Thus, it is concluded that an autocrine balance of positive and negative factors is important for maintaining controlled re-entry into dividing states from non-dividing states and that disruption of this balance leads to malignant progression characterized by greater independence of the malignant cells from the control of exogenous growth factors.

Gene Expression Regulation, Neoplastic↗

Repression of autocrine transforming growth factor beta 1 and beta 2 in quiescent CBS colon carcinoma cells leads to progression of tumorigenic properties.

Previous work has shown that repression of negative autocrine transforming growth factor (TGF) beta 1 did not alter the growth rate of a human colon carcinoma cell line, but the time required for the cells to enter exponential growth from lag phase was reduced (S. P. Wu, D. Theodorescu, R. Kerbel, J. K. V. Willson, K. M. Mulder, L. E. Humphrey, and M. G. Brattain, J. Cell Biol., 116: 187-196, 1992). These results have led to the hypothesis that the tumor suppressive activity of autocrine TGF-beta 1 was directed at quiescent nondividing cells rather than actively dividing cells. In order to test this hypothesis, a weakly tumorigenic, well-differentiated human colon carcinoma cell line designated CBS, which expressed autocrine TGF-beta 1 and -beta 2 activity in quiescent cells, but not in exponential growth phase cells, was identified. This cell line was stably transfected with a full-length TGF-beta 1 antisense complementary DNA. Constitutive expression of TGF-beta 1 antisense mRNA in CBS cells resulted in repression of autocrine TGF-beta 1 and -beta 2 protein activity in quiescent cells of approximately 10-fold. TGF-beta 2 repression could have been due to interaction with TGF-beta 1 antisense mRNA, since these two isoforms have a high degree of homology, or it could have been indirectly due to TGF-beta 1 repression, since this isoform has been shown to affect transcriptional and posttranscriptional control of TGF-beta 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Cell-mediated immune responses to poliovirus. I. Conditions for induction, characterization of effector cells, and cross-reactivity between serotypes for delayed hypersensitivity and T cell proliferative responses.

Human polioviruses are categorized into three distinct serotypes (types 1, 2, and 3) based upon their reactivity with specific antibodies. Although a great deal of information has been amassed about the induction and characterization of poliovirus antibody responses, little is known about cell-mediated immunity to poliovirus and its role in protection. Here, we show that intracutaneous injection of ultraviolet light-inactivated poliovirus into the tailbase of BALB/c mice induces delayed hypersensitivity (DTH) and T-cell proliferative (Tprlf) responses. Both DTH and Tprlf responses to poliovirus are mediated by Ly-1high2-, L3T4-bearing T cells. Moreover, known serologic cross-reactivity (i.e., antibody-mediated) of poliovirus serotypes is not predictive of cross-reactivity between the cell-mediated immune responses.

Animals↗

Epitope-specific regulation in Ir gene systems. I. Conditions for the induction of epitope-specific suppressors to poly(Glu60Ala30Tyr10).

Injection of responder mice with poly(Glu60Ala30Tyr10) (GAT) followed by immunization with GAT-methylated bovine serum albumin (GATMBSA) selectively suppresses anti-MBSA plaque-forming cell (PFC) and delayed hypersensitivity (DTH) reactions. Conversely, MBSA injection followed by GATMBSA immunization suppresses anti-GAT PFC and DTH, while anti-MBSA responses remain intact. Suppression occurs for doses of antigen which are optimally immunogenic. The suppression is specific and does not act in a bystander fashion. These results demonstrate that epitope-specific regulation is reciprocal, is not limited to humoral responses, and is not limited to molecules of low molecular weight.

Animals↗