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Biomedical subjects

F Shen

Publications and source records attributed to F Shen.

At least 91 records · Page 5Linked to original sources
PubMed1995

Molecular structure alteration of IgG increased anticomplementary activity of intravenous immunoglobulin.

AIM: To study the cause of anticomplementary activities (ACA) of intravenous immunoglobulins (IVIG). METHODS: ACA were determined by two assays (limit test and 100CH50 test), distributions of IgG molecular size (polymer, dimer, monomer and fragment) by HPLC, IgG subclasses and IgA contents by radial immunodiffusion, prekallikrein activator (PKA) and kallikrein (KK) activities by chromogenic assay, potency of antibody against hepatitis B surface antigen (Anti-HBs) by enzyme-linked immunosorbent assay (ELISA). RESULTS: The two ACA assays showed good correlation. However, ACA levels were not associated with distributions of IgG molecular size, IgG subclasses and IgA contents, PKA and KK activities. After heating incubation, ACA levels increased markedly and Anti-HBs decreased notably, distributions of IgG molecular size remained relatively constant. CONCLUSION: Molecular structure alteration of IgG increased spontaneous complement activation of IVIG.

Complement Activation↗
PubMed1994

Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity.

The expression of a membrane-associated folate receptor (FR) was elevated in spleen samples from patients with chronic (CML) and acute (AML) myelogenous leukemias compared with normal spleen. Contrary to earlier reports, antibodies to a purified FR from placenta cross-reacted quantitatively with this protein in solution radioimmunoassays. Similar to FR-alpha (KB cells) and FR-beta (placenta), the protein was released from the membrane by phosphatidylinositol-specific phospholipase C, indicating a glycosylphosphatidylinositol (GPI) membrane anchor. Screening of a cDNA library from CML spleen with a heterologous murine FR cDNA and also amplification of FR cDNAs from spleen and bone marrow in CML, AML, chronic lymphocytic leukemia (CLL), and acute lymphocytic leukemia (ALL) by polymerase chain reaction (PCR) using degenerate oligonucleotides yielded cDNA clones representing FR-beta, a novel FR (type gamma), and an aberrant transcript of FR-gamma with a 2 base pair deletion resulting in a truncated 104-residue polypeptide; FR-alpha was not detected in these tissues. The cDNA for FR-gamma predicts a 243-residue polypeptide with an amino acid sequence homology of 71% and 79% with FR-alpha and FR-beta, respectively, a 23-residue amino-terminal signal peptide, and 3 potential sites for N-linked glycosylation. Transfection of COS-1 cells with the cDNA for FR-gamma resulted in low expression of a [3H]folic acid binding protein on the cell surface that was GPI-anchored. PCR analysis of total RNA from a number of normal and malignant tissues and cell lines indicated a limited tissue specificity of FR-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Interaction of a novel Tn (GalNAc alpha 1-->Ser/Thr) glycoprotein with Gal, GalNAc and GlcNAc specific lectins.

A naturally occurring Tn glycoprotein (Native ASG-Tn) with GalNAc alpha 1-->Ser/Thr as the only carbohydrate side chains, has been prepared from armadillo submandibular glands. In a quantitative precipitin assay, this glycoprotein completely precipitated Maclura pomifera (MPA), Vicia villosa B4 (VVL-B4) and Artocarpus integrifolia (Jacalin, AIL). It also reacted well with Helix pomatia (HPL) and Wistaria floribunda (WFL) and precipitated over 75% of the lectin nitrogen added, but poorly with Ricinus communis agglutinin (RCA1), ricin, peanut (Arachis hypogaea, PNA), Abrus precatorius agglutinin (APA) and Triticum vulgaris (WGA). This finding suggests that this novel Tn-glycoprotein may serve as a useful reagent for differentiating Tn and T specific monoclonal antibodies and lectins.

Acetylgalactosamine↗
PubMed1994

Interaction of hamster submaxillary sialyl-Tn and Tn glycoproteins with Gal, GalNAc and GlcNAc specific lectins.

Hamster submaxillary glycoprotein (HSM), one of the simplest glycoproteins among mammalian salivary mucins, is composed of approximately equivalent amounts of protein, hexosamine and sialic acid. The Thr and Ser residues in the protein core account for more than half of all of the amino acid residues, while Lys, Glu, Pro and Ala are the major components of the remaining portion of amino acids. The carbohydrate side chains of this mucous glycoprotein have mainly the NeuAc-GalNAc-(sialyl-Tn) sequence (HSM), and those of the desialylated product (HSM-Tn) are almost exclusively unsubstituted GalNAc residues (Tn determinants). The binding properties of sialyl-Tn (HSM) and asialo-HSM (HSM-Tn) glycoproteins were tested by precipitin assay with Gal, GalNAc and GlcNAc specific lectins. The HSM-Tn completely precipitated Vicia villosa (VVL both B4 and mixture of A and B), Maclura pomifera (MPL), and Artocarpus integrifolia (Jacalin) lectins; less than 2 micrograms of HSM-Tn were required for precipitating 50% of 5.0-6.3 micrograms lectin nitrogen added. HSM-Tn also reacted well with Helix pomatia lectin (HPL), Wistaria floribunda lectin (WFL) and Abrus precatorius agglutinin (APA) and precipitated in each case over 81% of the lectin nitrogen added. The reactivity of HSM-Tn with other lectins (Ricinus communis, RCA1; Dolichol biflorus, DBL; Viscum album, ML-I; Arachis hypogaea, PNA, and Triticum vulgaris, WGA) was weak or negligible. The activity of sialyl-Tn (HSM) was more restricted; HSM reacted well with Jacalin, moderately with MPL and VVL-B4, but was inactive or only weakly with the other lectins used. These findings indicate that HSM and its desialylated product (HSM-Tn) are highly useful reagents for the differentiation of Tn and T/Gal specific lectins and for anti-T, Tn and Af monoclonal antibodies.

Animals↗
PubMed1994

[Study of cytochemical properties in the nucleus paragigantocellularis lateralis of rats].

The distribution of cell bodies containing serotonin (5-HT)-, substance-P (SP)-, L-enkephalin (L-ENK)- and neuropeptide Y (NPY)-like immunoreactivity (IR) in the nucleus paragigantocellularis lateralis (PGCL) of the rat was studied immunocytochemically. Perikarya containing 5-HT-, SP- or L-ENK-IR were found throughout the rostro-caudal extent of the PGCL. Large, well-staining 5-HT cells densely clustered rather near the ventrolateral surface of the medulla. SP- and L-ENK-IR were distributed more extensively and located more lateraly. A few of perikary on containing NPY-IR were found primarily in the area from the medium to caudal region. The results provided morphological basis for further study of the neurochemical properties of PGCL neurons involved in the regulation of cardiovascular, respiratory and other functions in the rat.

Animals↗
PubMed1993

Pattern of aromatic and hydrophobic amino acids critical for one of two subdomains of the VP16 transcriptional activator.

Structural features of the transcriptional activation domain of the herpes simplex virion protein VP16 were examined by oligonucleotide-directed mutagenesis. Extensive mutagenesis at position 442 of the truncated VP16 activation domain (delta 456), normally occupied by a phenylalanine residue, demonstrated the importance of an aromatic amino acid at that position. On the basis of an alignment of the VP16 sequence surrounding Phe-442 and the sequences of other transcriptional activation domains, we subjected leucine residues at positions 439 and 444 of VP16 to mutagenesis. Results from these experiments suggest that bulky hydrophobic residues flanking Phe-442 also contribute significantly to the function of the truncated VP16 activation domain. Restoration of amino acids 457-490 to various Phe-442 mutants partially restored activity. Although the pattern of amino acids surrounding Phe-473 resembles that surrounding Phe-442, mutations of Phe-473 did not dramatically affect activity; in fact, Phe-475 appears more sensitive to mutations than does Phe-473. We infer that the two regions of VP16 (amino acids 413-456 and 457-490) possess unique structural features, although neither is likely to be an amphipathic alpha-helix or an "acidic blob." These results, considered with previous in vitro activation and inhibition studies, suggest that the two subdomains of VP16 affect transcription by different mechanisms.

Amino Acid Sequence↗
PubMed1992

Differential stereospecificities and affinities of folate receptor isoforms for folate compounds and antifolates.

Two membrane folate receptor (MFR) isoforms are present in human tissues i.e. MFR-1 (e.g. placenta) and MFR-2 (e.g. placenta, KB cells, CaCo-2 cells). MFR-1 was expressed in COS-1 cells and the resulting protein had the same polypeptide molecular weight as the native protein. The affinities of (6S) and (6R) diastereoisomers of N5-methyltetrahydrofolate, N5-formyltetrahydrofolate, and 5,10-dideazatetrahydrofolate as well as folic acid and methotrexate to MFR-1, MFR-2 and placental MFR (MFR-1 plus MFR-2) were determined in terms of the Ki values for their competitive inhibition of the binding of [3H]folic acid to these proteins. The results indicated a striking difference in the stereospecificity of MFR-1 and MFR-2 for reduced folate coenzymes; MFR-2 preferentially bound to the physiological (6S) diastereoisomers and MFR-1 bound preferentially to the unphysiological (6R) diastereoisomers, while dideazatetrahydrofolate did not show significant stereospecificity for MFR-1. Furthermore, MFR-2 displayed significantly (2- to 100-fold) greater affinities for all the compounds tested compared to MFR-1. Purified placental MFR, a natural source of MFR-1 which contains variable amounts of MFR-2, showed intermediate Ki values for the compounds tested compared with MFR-1 and MFR-2 and stereospecificities similar to MFR-1. These observations demonstrate striking differences in the ligand binding sites of MFR-1 and MFR-2 which could potentially be exploited in the design of MFR isoform specific antifolates.

Animals↗
PubMed1992

[Influenza surveillance].

From 1982 to June 1990, seven influenza A (H3N2) epidemics and four influenza A (H1N1) epidemics occurred in Shanghai, and several new variants of influenza virus were isolated. During that period, influenza A (H3N2) and influenza A (H1N1) appeared alternatively while each lasted for one to two years. The epidemic peak of influenza usually was seen from July to August and late winter to early spring. The subtype which appears in July and August usually starting in late winter and early spring in Shanghai causes epidemics in the northern regions of China and some other countries in the northern hemisphere. If minor epidemics occur only in July and August, further antigenic changes may cause moderate epidemics in late winter and next early spring. Information supplied for prediction of influenza epidemics and timely preparation of new vaccines may lead to better control of influenza.

Antigenic Variation↗
PubMed1991

Spatial frequency of the human short-wavelength-sensitive (blue) cone mechanism. Psychophysical studies and pattern-reversal visual evoked potentials.

The interactions of spatial and chromatic processing of the short-wavelength-sensitive cone mechanism were studied in humans with patterned (checkerboard) stimuli of various spatial frequency (10, 22, 44, and 85 min of are respectively), under steady exposure to yellow light (575 nm, 390 cd/m2). Psychophysical studies and pattern-reversal visual evoked potentials were employed. Parameters of the transient pattern-reversal visual evoked potentials (pattern reversal rate of 2.4 s-1) especially observed were the latencies of P2 (P100) and N3 and the amplitude of P2-N3. It was only with the largest applicable check size (85 min of arc) that both the psychophysical studies and visual evoked potentials could succeed in satisfactorily isolating the short-wavelength-sensitive cone mechanism. Pattern-reversal visual evoked potential latencies are recommended in the evaluation of this cone mechanism because of their smaller variance and higher selectivity in isolating the short-wavelength-sensitive cone mechanism than the amplitude. The peak sensitivity of this cone mechanism was shown to be about 449 nm at the corneal level. The short-wavelength sensitive cone mechanism represented the characteristics of low spatial resolution and long latencies of the pattern-reversal visual evoked potentials.

Adult↗
PubMed1989

Impedance of arterial system simulated by viscoelastic t tubes terminated in windkessels.

An improved asymmetric t-tube model of the arterial system is proposed. The model consists of two viscoelastic tubes of differing lengths, each terminated in a modified windkessel with inductance as well as resistance and compliance. Equations for calculating the input impedance of this model are presented. Using typical data from the literature, the model predicts a more realistic impedance modulus and phase than previous models of the circulation. Parametric analysis shows that when peripheral compliances are altered, sharp peaks in the very low frequency portions of the impedance spectra are produced, whereas alterations of either the characteristic impedances or inductances of the terminations have little effect on input impedance. Alteration of the elasticity or relative lengths of the tubes results in shifts in the positions of the maxima and minima akin to those observed experimentally. Change in the viscosity of the walls or of the blood only affects the fluctuations of the impedance spectra without affecting the positions of the maxima and minima. Thus, with this still simple model, very realistic impedance spectra are obtainable. The model provides more insight than previously proposed models into the individual influence of various parameters of the proximal and peripheral vasculature on central hemodynamics.

Arteries↗
PubMed1983

Home dialysis and dialysis treatment modalities in the VA system.

A questionnaire was sent to 50 Veterans Administration dialysis centers to inquire about treatment utilization in preparation for a Cooperative Dialysis Study. Thirty-five completed questionnaires in this survey identified a dialysis population of 2,483 patients including 452 contract patients (13.5%). The number of patients treated in-center was 1,101 (48.5%), including 239 on self-care (10.2%), and 930 patients (38.0%) were dialyzed at home. This high utilization rate of home dialysis appears in excess of three times the prevalence of home dialysis experienced overall in non-VA programs. Identification of factors responsible for the present emphasis on home programs in the VA and a corresponding analysis of non-VA programs should provide important information for the planning of future national ESRD policies.

Ambulatory Care Facilities↗
PubMed1976

Precipitation of abstinence-like syndrome in morphine-dependent mice by pargyline.

In mice rendered morphine-dependent by pellet implantation for 3 days, the administration of pargyline 6 hours after pellet removal intensified narcotic abstinence behavior, particularly the narcotic withdrawal jumping response. Pargyline, 75 mg/kg i.p., caused a 6- to 9-fold increase in the incidence of jumping in mice withdrawing from morphine 6 hours after removal of the pellet, whereas this effect was not observed: 1) 1 hour after the injection of pargyline or 2) in animals still implanted with the morphine pellet. The median effective dose (ED50) of pargyline required to elicit withdrawal jumping in mice implanted with morphine decreased with increasing physical dependence. The ED50 for 72 hours was about one-sixth that after 24 hours of implantation. Additionally, pargyline potentiated naloxone-precipitated withdrawal jumping as evidenced by a reduction of the naloxone ED50 by approximately one-half. Administration of other monoamine oxidase inhibitors such as pheniprazine, iproiazid or tranylcypromine failed to alter the indicence of jumping in dependent mice undergoind abrupt morphine with drawal. Further, dopamine receptor stimulation by amphetamine, pheniprazine or amantadine antagonized the pargyline-induced jumping response. These data suggest that the increased incidence of withdrawal jumping observed after pargyline in morphine-dependent mice is not related to monoamine oxidase inhibition but rather to a possible pargyline-induced decrease in dopaminergic activity.

Amantadine↗
PubMed1968

Morphine tolerance, physical dependence, and synthesis of brain 5-hydroxytryptamine.

Tolerance and physical dependence development to morphine in mice can be prevented by concomitant administration of cycloheximide. The fact that the rate of synthesis of brain 5-hydroxytryptamine (5HT) increases with tolerance to morphine suggests that the protein involved may be associated with 5HT synthesis. Inhibition of this synthesis with p-chlorophenylalanine markedly decreases tolerance and physical dependence development to morphine.

Animals↗
PubMedDate not supplied

Tamoxifen and genistein synergistically down-regulate signal transduction and proliferation in estrogen receptor-negative human breast carcinoma MDA-MB-435 cells.

PURPOSE: Tamoxifen and genistein were tested for synergism in estrogen receptor- negative human breast carcinoma MDA-MB-435 cells because the two compounds decrease signal transduction activity through different biochemical mechanisms and arrest the cell cycle at different phases. MATERIALS AND METHODS: The combination effect of tamoxifen and genistein on signal transduction was determined by measuring IP3 concentrations and on cell proliferation and colony formation by growth inhibition assay and clonogenic assay. RESULTS: In growth inhibition assays, for tamoxifen and genistein in the carcinoma cells the IC50s were (mean +/- SE) 17 +/- 0.9 and 27 +/- 1.6 microM; in clonogenic assays the LC50s were 0.9 +/- 0.4 and 12.5 +/- 1.1 microM, respectively. When tamoxifen and genistein were simultaneously added to the cells, synergism was observed in growth inhibition, in cytotoxicity and in the reduction of inositol 1,4,5-trisphosphate concentration. CONCLUSION: The synergistic down-regulation of signal transduction by tamoxifen and genistein may explain, in part at least, the synergistic antiproliferative and cytotoxic actions of the two compounds. The synergism of tamoxifen and genistein may be of interest in the clinical treatment of breast carcinoma.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Regulation of signal transduction activity in normal and cancer cells.

UNLABELLED: The purpose of this investigation is to clarify critical aspects of the behavior and regulation of signal transduction activity in normal and cancer cells. MATERIALS AND METHODS: Signal transduction activity was determined by measuring the steady-state activity of the three synthetic enzymes involved in the conversion of 1-phosphatidylinositol to IP3, PI 4-kinase, PI 4-phosphate 5-kinase and phospholipase C. These enzymic activities were opposed by the activities of the degradative enzymes, 4-phosphatase and 5-phosphatase. RESULTS: We observed in hepatocellular carcinomas the operation of an integrated imbalance in signal transduction which was manifested in the up-regulation of the steady-state activities of the three synthetic enzymes and in the reduction of the activities of the two catabolic phosphatases. As a consequence of this enzyme imbalance there was an increase in the concentration of IP3 in hepatomas. Increased IP3 levels were also observed in numerous human carcinomas in clinical samples and in tissue culture cells. The signal transduction activity was subject to nutritional regulation and to drug action. The elevated signal transduction activity, as measured by the IP3 concentration, was down-regulated in a time- and dose-dependent fashion by the anticancer drug, tiazofurin, by the flavonoids, quercetin and genistein, and by the anti-estrogen receptor, tamoxifen. CONCLUSIONS: Our studies show that signal transduction activity is stringently linked with transformation and progression in rat and human carcinomas. Down-regulation of signal transduction activity by various drugs led to a marked reduction of IP3 concentration and then to apoptosis and induced differentiation.

Animals↗
PubMedDate not supplied

Amplified increase in signal transduction activity in cancer cells.

AIM: To elucidate the behavior of 1 phosphatidylinositol 4,5 bisphosphate (PIP2) 5 phosphatase (PIP2 5-Pase, EC 3.1.3.36) and 1 phosphatidylinositol 4 phosphate (PIP) 4-phosphatase (PIP 4-Pase) in cancer cells, the steady state activities of PIP2 5-Pase and PIP 4-Pase were determined in the particulate fractions of rat liver and in a spectrum of rat hepatomas of different growth rates and malignancy. METHODS: A standard method was developed using exogenous PIP2 or PIP as substrates. RESULTS AND DISCUSSION: One half of the maximum activities was reached at about 0.3 mM of the substrates and at 0.1 to 0.2 mM magnesium chloride. The optimum concentrations of Triton X-100 and cetyltrimethyl ammonium bromide were 0.25% (w/v) and 1 mM, respectively. PIP2 5-Pase and PIP 4-Pase activities were linear with time for 20 min and proportional with protein concentrations up to 22 micrograms per 50 microliters reaction mixture. In rat liver the steady state activities of PIP2 5-Pase and PIP 4-Pase were 1849 to 1881 and 1394 to 1670 nmol/h/mg protein. In three rat hepatomas the enzyme activities decreased to 50-51% and 33-42%, respectively. These results and our earlier data showing increased 1 phosphatidylinositol 4 kinase (EC 2.7.1.67), PIP 5-kinase (EC 2.7.1.68) and phospholipase C, PIP2 phosphodiesterase (EC 3.1.4.11) activities provide evidence of a transformation linked amplified increased capacity in signal transduction activity in cancer cells. The discovery and documentation of this integrated imbalance in regulation in phosphoinositide metabolism in cancer cells are in line with our observations in cancer cells for enzymes of purine and pyrimidine metabolism. The amplified increase in signal transduction capacity in cancer cells provides novel targets for the development of anticancer drugs.

Animals↗