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Biomedical subjects

Q Cheng

Publications and source records attributed to Q Cheng.

At least 109 records · Page 6Linked to original sources
PubMed1997

Assessment of the humoral immune response against Plasmodium falciparum rhoptry-associated proteins 1 and 2.

Naturally occurring antibody responses to Plasmodium falciparum rhoptry-associated proteins 1 and 2 (RAP-1 and RAP-2) were measured with recombinant and parasite-derived forms of the antigens. For comparative purposes, responses to multiple forms of three other malarial antigens were also examined. The sera of 100 Papua New Guineans were screened for antibodies. Eighty-six and 82% of individuals over 30 years of age had antibodies that recognized parasite-derived RAP-1 and RAP-2, respectively. Importantly, we found that recombinant and native antigens share linear epitopes seen by the human immune system; thus, the recombinant proteins may be adequate human immunogens. However, antibodies affinity purified on recombinant RAP-1 reacted with other antigens in addition to parasite-derived RAP-1. Thus, the antigenicity of RAP-1 may have been overestimated previously. The recognition of RAP-1 and RAP-2 correlated with age and with the recognition of recombinant forms of the ring-infected erythrocyte surface antigen, merozoite surface protein 1, and merozoite surface antigen 2 (MSA2) antigens. Antibodies to these antigens appear to be generated in response to the total exposure to malaria of the host. Antibodies to conserved regions of MSA2 had stronger correlations with both age and the recognition of other antigens than did the full-length recombinant MSA2 molecule. In contrast to results with the other antigens, there was no significant difference in the ages of individuals with a certain antibody titer to the full-length recombinant or parasite-derived MSA2 molecule, but antibodies to these two antigens did correlate with parasitemia. For all antigens tested, antibody levels after two infections can approach the peak levels of antibodies obtained in immune individuals.

Adolescent↗
PubMed1997

Epidemiological features of Guillain-Barré syndrome in Sweden, 1978-93.

OBJECTIVES: To describe the incidence of Guillain-Barré syndrome in Sweden during the period 1978-93 and its temporal and geographical variations. METHODS: Stratified and Poisson regression analyses and tests for detection of small epidemics were applied to population based hospital discharge data from 2257 incident cases of Guillain-Barré syndrome in Sweden during the study period. RESULTS: The incidence of Guillain-Barré syndrome was (1) 1.77 per 100000 person-years when age adjusted to the European population; (2) higher in males; and (3) stable across time, although occasional increases of annual incidence rates were found-namely, in 1978 (relative risk (RR) 1.30 (95% CI 1.10-1.54)), and in 1983 (RR 1.24 (95% CI 1.06-1.40)). The incidence increased with age and was bimodal, with peaks at 20-24 and 70-74 years. There was a moderate but significant seasonality with a peak in August, particularly among the young age groups. The age adjusted incidence by county varied from 1.11 to 2.57 per 100000 person-years. Neither temporal nor spatial clustering was significant, except during the period July-September in 1983 at ages below 40 years. CONCLUSIONS: The incidence of Guillain-Barré syndrome in Sweden during the period 1978-93 had a magnitude similar to those described in other surveys, a bimodal distribution by age, and modest geographical and temporal variations with significantly high rates in 1978 and 1983 and in autumn. Minor outbreaks might have passed unnoticed up to the present. Whereas reported drug induced cases of Guillain-Barré syndrome may in part explain the high incidence in 1983, the cause of the aberrant incidence in 1978 remains unknown. Epidemiological surveillance of Guillain-Barré syndrome in Sweden might have been useful.

Adult↗
PubMed1997

Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines.

Several prototype vaccines against the asexual blood stage of malaria are undergoing preclinical and phase I testing. Although these vaccines have been chosen for their ability to elicit an anti-parasite response, no practical and sensitive clinical trial procedure has been available for measuring their impact on parasite growth. We describe a system that allows parasite growth rates to be measured in volunteers through the incubation period. Two necessary elements of this system are developed: suitable blood-stage Plasmodium falciparum inocula, and a highly sensitive and quantitative assay to measure parasite growth during the incubation period. We infected five nonimmune volunteers with an inoculum as small as 300 parasites and demonstrated that the resultant in vivo asexual parasite growth rates were reproducible at 12-15-fold per cycle. The system allowed the infection to be followed for eight days before treatment without symptoms developing. These findings suggest that it is feasible to directly measure the anti-parasite efficacy of a prototype malaria vaccine in human volunteers without subjecting them to the risk of disease.

Adult↗
PubMed1997

[Cardiac operation via subaxillary and anterolateral subaxillary thoracotomy with cardiopulmonary bypass].

From March 1995 to August 1996, 50 patients underwent cardiac operation through subaxillary and anterolateral subaxillary thoracotomy with cardiopulmonary bypass. 17 had atrial septal defect, 26 ventricular septal defect, 3 mitral stenosis and insufficiency, 1 isolated mitral insufficiency, 1 double chamber of right ventricle, 1 partial common atrioventricular canal, and 1 cor atriatriatum. All operations were successfully performed without technical difficulty. The cardiopulmonary bypass time was 40.19 +/- 17.17 minutes with aortic cross-clamping time of 22.59 +/- 11.06 minutes. There were no operative death and complications. In conclusion, the subaxillary and anterolateral subaxillary thoracotomy incision appears to be a minimally invasive, safe, effective and cosmetic alterative to median sternotomy for cardiac operation.

Adolescent↗
PubMed1997

[Synthesis and antifungal activities of 1-(1-substitutedphenyl)-2-(1H-1,2,4-triazol or benztriazol-1-yl)-O-(substitutedbenzyl) ethanoximes].

Twenty-nine 1-(1-substituted phenyl)-2-(1H-1,2,4-triazol or benztriazol-1-yl)-O-(substituted benzyl) ethanoximes have been synthesized for the first time. Results of preliminary biological test in vitro show that most compounds have antifungal activities against most fungi tested. The antifungal activities of compounds T1, T4, T6, T11, T12, B1, B3, B4 and B6 are better than or comparable to the activities of the lead compound oxiconazole against some fungi.

Antifungal Agents↗
PubMed1997

[Effects of sevoflurane on contractility of isolated thoracic aorta rings in rabbits].

The objective of this paper was to observe the effects of sevoflurane on isolated rabbit aortic rings and the mechanisms of the effects. Twenty-four vascular rings collected from different New Zealand rabbits were randomly divided into 4 groups: Group 1 endothelium-inact rings; Group 2 endothelium-denuded rings; Group 3 endothelium-intact rings plus indomethacin; Group 4 endothelium-denuded rings plus indomethacin. When stable active tension produced by phenylephrine (1 x 10(-6) mol.L-1) was obtained, sevoflurane was added into the tissue bath. The anesthetic gas was increased in 0.5% increments every 10 min until the 4% of sevflurane after which 5% was administered. In rings of Group 3 and Group 4, indomethacin (2.8 x 10(-5) mol.L-1) was added to the bath 10 min before the addition of sevoflurane. The results showed that sevoflurane relaxed all groups of rings dose-dependently and this action was non-endothelium dependent and indomethacin had no effect on it. It suggests that sevoflurane relaxes peripheral vessels perhaps by affecting vascular muscle directly.

Anesthetics, Inhalation↗
PubMed1996

Stimulation of phosphorylase phosphatase activity of protein phosphatase 2A1 by protamine is ionic strength dependent and involves interaction of protamine with both substrate and enzyme.

The effects of protamine on the phosphorylase phosphatase activity of porcine cardiac protein phosphatase 2A1 (PP2A1) were complex and ionic strength dependent. Under ionic strength conditions that protamine activation was optimal, activation of PP2A1 by either dilution or heparin was prevented. A time-dependent deactivation of the protamine-stimulated phosphatase activity was observed when PP2A1 was preincubated with protamine. Protamine forms a very tight association with phosphorylase a, which is optimal at a 1:1 protamine:phosphorylase a monomer molar ratio. Protamine activation of PP2A1 activity, however, is not substrate-directed since the basic polypeptide did not stimulate either the activity of the catalytic subunit or trypsinolysis of [32P]phosphorylase a. The interaction of protamine with phosphorylase a does not apparently involve the phosphorylation site in the protein substrate (ser 14). The activation of PP2A1 by protamine is proposed to involve part of the basic polypeptide, not associated with phosphorylase a monomer, interacting with the regulatory and/or the catalytic subunit(s) of the phosphatase. A minimal model for the activation of PP2A1 by protamine was tested kinetically. In this model, free PP2A1 binds with decreasing affinities to the protamine:phosphorylase a complex, free phosphorylase a, and free protamine. Protamine decreases the K(m) of PP2A1 for the phosphorylase a monomer 5-fold and increases the Vmax 17-fold. Interaction of free protamine with PP2A1 inhibits the phosphatase activity.

Animals↗
PubMed1996

A 'litmus test' for molecular recognition using artificial membranes.

BACKGROUND: Sensitive and selective molecular recognition is important throughout biology. Certain organisms and toxins use specific binding at the cell surface as a first step towards invasion. A new series of biomolecular materials, with novel optical and interfacial properties, have been designed to sense molecular recognition events. These polymers, the diacetylenic lipids, have previously been shown to undergo chromatic transitions in response to virus binding to the surface of the material. RESULTS: Gangliosides that specifically bind cholera toxin, heat-labile Escherichia coli enterotoxin and botulinum neurotoxin were incorporated into a matrix of diacetylenic lipids, 5-10% of which were derivatized with sialic acid. The lipids were self-assembled into Langmuir-Blodgett layers and polymerized with ultraviolet irradiation, yielding a polydiacetylene membrane with a characteristic blue color into which the ganglioside is non-covalently incorporated. When toxin is added, the polymerized membrane turns red. The response is specific and selective, and can be quantified by visible absorption spectrophotometry. CONCLUSIONS: Polydiacetylenic lipid membranes offer a general 'litmus test' for molecular recognition at the surface of a membrane. A concentration of 20 ppm of protein could be detected using polymerized thin films. The speed, sensitivity and simplicity of the design offers a new and general approach towards the direct colorimetric detection of a variety of different molecules.

Biosensing Techniques↗
PubMed1996

Experimental human Plasmodium falciparum infections: longitudinal analysis of lymphocyte responses with particular reference to gamma delta T cells.

The kinetics of the gamma delta T-cell response was analysed in the context of the overall haematological response in subjects experimentally infected with sporozoites of Plasmodium falciparum. Numbers of gamma delta and alpha beta T cells and NK cells declined markedly during infection to reach minimum values 12-13 days post-infection when the patients were ill. This decline commenced from the beginning of the erythrocytic cycle and well before parasites could be detected microscopically and clinical symptoms developed. Platelet numbers also declined. In vivo activation of gamma delta T cells was evident with sequential up-regulation of the activation markers CD69 and HLA-DR. gamma delta T cell numbers were highest after treatment with the majority being CD4-CD8-, HLA-DR+ and showing reduced CD45RA expression. Contrary to some published observations gamma delta T-cell percentages remained within the normal range. Little evidence of upregulation of activation or memory markers was observed in the alpha beta T-cell population. In vitro proliferative responses to malaria antigen which involve gamma delta T cells were lost as the infection progressed and the lymphocyte count declined but these could be restored with the addition of exogenous IL-2 to cultures. The authors findings are consistent with a protective and/or immunomodulatory role for gamma delta T cells in malaria.

Adult↗
PubMed1996

The effects of growth factors on Tenon's capsule fibroblasts in serum-free culture.

This study was performed to develop and improve a completely defined in vitro ocular wound-healing model of fibroblast proliferation for glaucoma filtration surgery. This model is essential for the investigation of protein-sensitive drugs and cytokines. Tenon's capsule fibroblasts in their third passage were incubated overnight, washed free of serum, and fed defined media, Aim V or Clonetics FBM serum-free medium containing platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, or fibronectin at various dilutions and in combinations at optimum concentrations. Proliferation was measured by 3H-thymidine incorporation at 1, 3, and 7 days. Morphology was compared to controls fed Minimum Essential Medium + 10% serum. Single factors stimulated the greatest amount of thymidine uptake on day 3. Optimum concentrations were epidermal growth factor at 5 ng/ml, basic fibroblast growth factor at 10 ng/ml and platelet-derived growth factor at 20 ng/ml. Identical combinations of factors stimulated nearly twice the thymidine uptake in Clonetics medium as in Aim V. Epidermal growth factor activity was inhibited by either basic fibroblast growth factor or platelet-derived growth factor. Basic fibroblast growth factor and platelet-derived growth factor together produced a less than additive effect. The performance of either serum-free medium may be improved by the addition of basic fibroblast growth factor or platelet-derived growth factor. The optimum serum-free medium (Clonetics FBM) with growth factors was unable to stimulate proliferation as much as Minimum Essential Medium + 10% NBS, but was successful in maintaining viability during the 7 day test period.

Cell Division↗
PubMed1996

[The modulation of renal tubular epithelial cells treated with hypoxia on renal interstitial fibroblasts in coculture].

UNLABELLED: To clarify cell-cell interaction in the pathogenesis of renal tubulointerstitial nephritis (TIN), the effect of renal tubular epithelial cells (TEC) on renal interstitial peritubular fibroblasts (PTF) was examined in cell coculture system without direct contact. TEC and PTF were prepared from the kidney of BALB/C mice. Firstly, TEC were plated into intercup chambers of 24-well plates and incubated at 37 degrees C in a humidified 5% CO2 atmosphere for 72 hours. Then the cells were cultured in an incubator which was full of 95% N2 for 24 hours. Secondly, those intercups with hypoxia-treated TEC were floated on the wells of 24-well plates containing PTF which had been incubated for 24 hours. The TEC and the PTF were cocultured for another 48 hours. PTF were also cocultured with normal TEC as controls. The parameters of the cocultured PTF were measured as follows. (1) Cell proliferation examined by MTT incorporation method and the cell numbers were detected with total acid phosphatase activity. (2) Fibronectin (FN), laminin (LN) and collagen IV in the supernatants of coculture system were measured by ELISA method. (3) The distribution of ICAM-1 on the cell membrane of PTF was determined by laser confocal scanning microscopy. RESULTS: (1) The number of PTF cocultured with hypoxiatreated TEC was greater than that of controls (P < 0.01). (2) The level of FN and LN in the supernatants of the PTF cocultured with hypoxia-treated TEC was higher than that of the controls (P < 0.05). (3) The expression of ICAM-1 on PTF cocultured with hypoxia-treated TEC was higher than that of controls (P < 0.01). In conclusion the interaction of PTF and TEC may play a role in the pathogenesis of TIN.

Animals↗
PubMed1995

A continuous spectrophotometric assay for phosphorylase kinase.

A continuous spectrophotometric assay for the determination of the initial rate of the phosphorylase kinase catalyzed reaction at pH 7.0 is presented. The assay incorporates two coupling enzyme systems: (a) recombinant rabbit skeletal muscle type 1 protein phosphatase catalytic subunit which dephosphorylates the phosphorylase a product of the phosphorylase kinase reaction, and (b) the system of Webb (Proc. Natl. Acad. Sci. USA 89, 4884-4887, 1992), which uses purine nucleoside phosphorylase and its chromophoric substrate, 7-methyl-6-thioguanosine, for the quantitation of the resultant inorganic phosphate. The effects of reaction components on the enzyme activities were studied. The system was standardized and validated. The continuous coupled enzyme system was used for the kinetic analysis of nonactivated phosphorylase kinase at pH 7.0. Km and kcat values of 15.36 +/- 0.2 microM (phosphorylase b monomer) and 21 +/- 1.12 s-1, respectively, were determined.

Animals↗
PubMed1995

A continuous spectrophotometric assay for protein phosphatases.

A continuous spectrophotometric assay for the determination of protein phosphatase activity is presented. The assay incorporates the coupled enzyme system of Webb (M. R. Webb, 1992, Proc. Natl. Acad. Sci. USA 89, 4884-4887), which used purine nucleoside phosphorylase and the chromophoric substrate 7-methyl-6-thioguanosine for the quantitation of inorganic phosphate. The assay is exemplified and validated here for the phosphorylase phosphatase activity of protamine-stimulated protein phosphatase 2A1 (PP-2A1). The effects of reaction components on the activities of both PP-2A1 and purine nucleoside phosphorylase were studied. The application of the coupled assay system to kinetic analysis of the phosphorylase phosphatase activity of PP-2A1 and to the assay of the catalytic subunits of type 1 and 2A protein phosphatases and a recombinant type 1 catalytic subunit is demonstrated. The applicability of this coupled enzyme system to the assay of other protein phosphatases is discussed.

Animals↗
PubMed1995

Characterization of tumor-specific cytotoxic effector cells with a novel CD3-/Thy-1+ phenotype.

The introduction and expression of allogeneic MHC class I genes in tumors can generate tumor-specific immunity which subsequently results in the regression of parental tumors. Immunization of naive (AKR/J x C57BL/6)F1 mice with H-2Kb-transformed K36 tumor cells was found to render recipient mice immune to a subsequent challenge by parental K36 tumor cells. Two types of cytotoxic T effector cells were demonstrated in these immune mice. One of the cytotoxic effector cells generated against the K36 tumor cells is the conventional CD3+ cells, and these account for approximately one-third of the total observed tumor-specific cytotoxicity in vitro. The other cytotoxic effector cell generated following the immunization of (AKR/J x C57BL/6)F1 mice with the H-2Kb-transformed K36 cells had the CD3-/Thy-1+ phenotype, and accounted for the remaining two-thirds of the observed tumor-specific cytotoxicity in vitro. These CD3-/Thy-1+ cells can lyse parental K36 tumor cells in a tumor-specific fashion, and tumor-specific immunity can be adoptively transferred to naive animals via the CD3-/Thy-1+ cells. In contrast to CD3+ CTL, CD3-/Thy-1+ cells express CD45RBlow, Ly-6Chigh, and HSA molecules. Although the CD3-/Thy-1+ cells can be activated in vitro by IL-2, TPA, and ionomycin, they cannot be propagated in vitro. The CD3-/Thy-1+ cells undergo apoptosis following prolonged culture in vitro. At present, the exact mechanism(s) by which CD3-/Thy-1+ cells can mediate tumor-specific cell lysis in the absence of identifiable T cell receptor molecules is unknown; nevertheless, these data suggest the existence of a novel T cell type to combat tumors.

Animals↗
PubMed1995

Comparative efficacy of antiviral drugs on human ocular fibroblasts.

The effects of several antiviral drugs on fibroblast attachment and proliferation from human Tenon's capsule were investigated. These drugs included purine nucleoside analogs, vidarabine and acyclovir (ACV); pyrimidine nucleoside analog, AZT; and a synthetic cyclic primary amine, amantadine. Fibroblast attachment and proliferation inhibition were determined by Coulter counter, a colorimetric assay of the enzyme hexosaminidase, and a 3H-thymidine uptake assay. Amantadine and AZT inhibited fibroblast attachment at concentrations higher than 6.61 x 10(-4)M and 3.73 x 10(-4) M, respectively. Amantadine and AZT had inhibitory effects on fibroblast proliferation as early as day 1, whereas vidarabine and ACV manifested their inhibitory effects after day three by Coulter counter and hexosaminidase assays. For amantadine, AZT, ACV and vidarabine, the 50% inhibitory dose (ID50) were 4.94 x 10(-5) M, 1.26 x 10(-5) M, 4.60 x 10(-4) M, and 1.52 x 10(-5) M at day 9, respectively, as measured by 3H-thymidine uptake assay. All four antiviral agents tested had inhibitory effects on human ocular fibroblast proliferation and their inhibitory potential decreased in the order of amantadine > or = vidarabine > AZT > or = ACV.

Acyclovir↗
PubMed1995

Use of suppressor analysis to find genes involved in the colonization deficiency of a Bacteroides thetaiotaomicron mutant unable to grow on the host-derived mucopolysaccharides chondroitin sulfate and heparin.

Bacteroides thetaiotaomicron, one of the numerically predominant species of human colonic bacteria, can ferment two types of host-derived mucopolysaccharides, chondroitin sulfate (CS) and heparin (HP). Originally, the pathways for utilization of CS and HP appeared to be completely independent of each other, but we have recently identified a gene, chuR, that links the two utilization systems. chuR is probably a regulatory gene, but it controls only a small subset of genes involved in CS and HP utilization. Some of the genes controlled by chuR are important for survival of B. thetaiotaomicron in the colon because a mutant that no longer produced ChuR was unable to compete with the wild type for colonization of the intestinal tract of germfree mice. In an attempt to identify genes that either were controlled by ChuR or encoded proteins that interacted with ChuR, we used transposon mutagenesis to generate suppressor mutations that restored the ability of a chuR disruption mutant to grow on CS and HP. Two classes of suppressors were isolated. One class grew as well as the wild type on CS and HP and had recovered the ability to compete with the wild type for colonization of the germfree mouse intestinal tract. A second class grew more slowly on CS and HP and reached only a half-maximum level on CS. This mutant still had a colonization defect. Representatives of both classes of suppressor mutants have been characterized, and the results of this analysis suggest that the transposon insertions in the suppressor mutants probably affected regulatory genes whose products interact with ChuR.

Bacterial Proteins↗
PubMed1995

Identification and characterization of a Bacteroides gene, csuF, which encodes an outer membrane protein that is essential for growth on chondroitin sulfate.

Bacteroides thetaiotaomicron can utilize a variety of polysaccharides, including charged mucopolysaccharides such as chondroitin sulfate (CS) and hyaluronic acid (HA). Since the enzymes (chondroitin lyases I and II) that catalyze the first step in breakdown of CS and HA are located in the periplasm, we had proposed that the first step in utilization of these polysaccharides was binding to one or more outer membrane proteins followed by translocation into the periplasm, but no such outer membrane proteins had been shown to play a role in CS or HA utilization. Previously we have isolated a transposon-generated mutant, CS4, which was unable to grow on CS or HA but retained the ability to grow on disaccharide components of CS. This phenotype suggested that the mutation in CS4 either blocked the transport of the mucopolysaccharides into the periplasmic space or blocked the depolymerization of the mucopolysaccharides into disaccharides. We have mapped the CS4 mutation to a single gene, csuF, which is capable of encoding a protein of 1,065 amino acids and contains a consensus signal sequence. Although CsuF had a predicted molecular weight and pI similar to those of chondroitin lyases, it did not show significant sequence similarity to the Bacteroides chondroitin lyase II, a Proteus chondroitin ABC lyase, or two hyaluronidases from Clostridium perfringens and Streptococcus pyogenes, nor was any CS-degrading enzyme activity associated with csuF expression in Bacteroides species or Escherichia coli. The deduced amino acid sequence of CsuF exhibited features suggestive of an outer membrane protein. We obtained antibodies to CsuF and demonstrated that the protein is located in the outer membrane. This is the first evidence that a nonenzymatic outer membrane protein is essential for utilization of CS and HA.

Amino Acid Sequence↗