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Biomedical subjects

A K Cheung

Publications and source records attributed to A K Cheung.

At least 91 records · Page 5Linked to original sources
PubMed1990

Humoral immune response to immediate-early protein of pseudorabies virus in swine with induced or naturally acquired infection.

Pseudorabies virus (PRV) immediate-early (IE) protein is a nonglycosylated polypeptide localized in the nuclei of infected cells. The IE protein is a regulatory protein that is only synthesized during viral replication and is presented to the immune system of PRV-infected swine. Antibodies to the IE protein were demonstrated in swine with induced or naturally acquired infection. However, antiserum raised against purified IE protein could not neutralize PRV in vitro.

Animals↗
PubMed1989

DNA nucleotide sequence analysis of the immediate-early gene of pseudorabies virus.

The complete DNA sequence coding for the immediate-early protein (IE180) of pseudorabies virus was determined. The coding region of IE180 is 4380 nucleotides for 1460 amino acid residues. G+C content of the non-coding portion of the IE gene is 70.3% while the G+C content of the coding portion is considerably higher at 80.1%. Correspondingly, codons consisting mainly of Gs and Cs are favoured. Clusters of amino acid homologies are observed among IE180 of pseudorabies virus, ICP4 of herpes simplex virus type-1 and IE140 of varicella-zoster virus, and are organized similarly in all three polypeptides. Functions exhibited by IE180 are assigned, tentatively, to structural domains of the molecule by analogy to the HSV-1 ICP4 polypeptide.

Amino Acid Sequence↗
PubMed1989

Nucleotide sequence of coronavirus TGEV genomic RNA: evidence for 3 mRNA species between the peplomer and matrix protein genes.

The region of the TGEV genome between the E1-matrix protein gene and the E2-peplomer protein gene has been sequenced from a cDNA clone. The consensus recognition sequence, 5'TTAA CTAAAC was found upstream from 3 large open reading frames. In coronaviruses these homologous recognition sequences are involved in the initiation of transcription suggesting that there are 3 mRNA species in this region of the TGEV genome. Northern blot analysis and nuclease S1 mapping confirmed the presence of 3 mRNA species between mRNA 3 encoding the E2-peplomer protein and mRNA 6 encoding the E1-matrix protein. The 5' regions of these 3 mRNAs encode potential polypeptides of predicted molecular weight; 7859, 27744 and 9287, respectively. The potential translation product of ORF B (27744 Da) is considerably larger than previously reported and could be difficult to distinguish by size from the E1-matrix protein.

Animals↗
PubMed1989

Adsorption of unactivated complement proteins by hemodialysis membranes.

Hemodialysis using polyacrylonitrile (PAN) membranes has been reported to be associated with depletion of complement in the plasma, yet the increase in plasma C3a antigen concentrations and the degree of leukopenia are modest. These observations suggest that PAN membranes may have a large propensity to adsorb native complement proteins; as a consequence, complement depletion can occur without activation. In the present study, we observed that incubation of human serum in the presence of PAN membrane resulted in a 50% loss of serum hemolytic activity of C3. When radiolabeled purified components were offered, PAN membranes were found to adsorb C3 and C5 in a dose-dependent manner. Adsorption of these proteins by PAN was more than 20 times greater than adsorption by cuprophan, cellulose acetate or Hemophan (Akzo, formerly Enka, Wuppertal, FRG) at all concentrations examined. These results suggest that depletion of complement when serum is exposed to hemodialysis membranes may result from adsorption of complement components onto the membrane surfaces and does not necessarily indicate complement activation.

Acrylic Resins↗
PubMed1989

Activation of the alternative pathway of complement by cellulosic hemodialysis membranes.

Compared to cellulose acetate, hemodialysis with cuprophan membranes is associated with greater activation of the alternative pathway of complement. Previous studies have shown that this difference is not due to a greater number of potential covalent binding sites for activated C3 on cuprophan. To investigate further the factors that influence complement activation by hemodialysis membranes, proteins were eluted from serum-treated cuprophan and cellulose acetate membranes with hydroxylamine at alkaline pH and analyzed by SDS-PAGE and Western blot. Approximately 23 times more total protein was removed from cellulose acetate. Virtually all the C3 in the cellulose acetate eluate was in the form of inactive fragments C3c and C3dg. In contrast, the functionally active form of C3 (C3b) was a prominent constituent of the cuprophan eluate. The binding of factor B (precursor of the catalytic subunit of the C3 convertase) and factor H (regulatory protein of C3 activation) to serum-treated membranes was also analyzed. By Scatchard's method, the affinity constant at equilibrium for factor B binding (KB) to the two types of membranes was not significantly different; however, there were approximately four times more factor B binding sites on the cuprophan than on the cellulose acetate. For cuprophan, the number of factor B binding sites was 1.6 times greater than the number of factor H binding sites. These studies demonstrate that a portion of the C3b molecules that bind to cuprophan are protected from degradation, and suggest that the complement activating capacity of hemodialysis membranes is determined by biochemical properties that modulate both the binding of serum proteins to the membrane and the interactions of the endogenous regulatory proteins with membrane-associated C3b.

Cellulose↗
PubMed1989

Treatment of nephrotic hyperlipoproteinemia with gemfibrozil.

Hypercholesterolemia is a known complication of the nephrotic syndrome. Patients with persistent proteinuria and prolonged hypercholesterolemia are probably at increased risk for cardiovascular disease. Until recently there has been no safe and effective treatment for this disorder. The effects of gemfibrozil on plasma lipids and lipoproteins in hypercholesterolemic patients with the nephrotic syndrome were therefore studied. Eleven patients with the nephrotic syndrome were studied in a randomized, double-blind placebo-controlled trial with six-week treatment periods. Gemfibrozil 600 mg or placebo was administered twice a day. There was a third unblinded period in which seven patients received gemfibrozil plus the bile acid-binding resin, colestipol, 10 grams twice a day. Gemfibrozil treatment produced a marked reduction in plasma triglyceride (51%, P = 0.001) and a 15% decrease in plasma total cholesterol (P = 0.003). Low density lipoprotein cholesterol decreased 13% (P greater than 0.05), high density lipoprotein cholesterol increased 18% (P = 0.006) and the ratio of low density lipoprotein to high density lipoprotein cholesterol fell 26% (P = 0.01). Apolipoprotein A-l was unchanged while apolipoprotein B decreased 26% (P = 0.006). Four patients were unable to complete period 3 because of gastrointestinal symptoms. The remaining patients had further improvement in plasma lipids and lipoproteins with the combined therapy: total cholesterol further decreased 26%, triglycerides decreased 17%, low-density lipoprotein cholesterol decreased 36%, high-density lipoprotein to high-density lipoprotein cholesterol fell 33%. Gemfibrozil improved lipid and lipoprotein cardiovascular risk factors without major toxicity. Persistent elevations in total plasma and low-density lipoprotein cholesterol during gemfibrozil treatment, however, indicate the need for individualized drug therapy.

Adult↗
PubMed1989

Analysis of the complement C3 fragments associated with hemodialysis membranes.

During hemodialysis with cuprophan membranes, bioactive peptides are generated because the alternative pathway of complement is activated. When cellulose acetate membranes are employed, complement activation is attenuated. The molecular basis for this improved biocompatibility is unknown. It has been postulated, however, that the complement activating potential of dialysis membranes is influenced by the availability of free hydroxyl groups which would provide an acceptor site for activated C3. To investigate this hypothesis, the forms of C3 associated with cellulose acetate and cuprophan membranes have been analyzed. By Western blot, the predominant form of C3 present on both types of membranes is C3c, a degradation product of C3 that lacks the thiolester necessary for covalent bonding. Minimal amounts of C3d (the region of C3 which contains the thiolester) were observed on both membranes; however, by ELISA, there was no difference in the amount bound to cellulose acetate compared to cuprophan. Further, membrane-associated C3d could be removed by urea, suggesting that it was not bound covalently. These studies indicate that the complement activating potential of dialysis membranes is not determined primarily by the availability of potential covalent binding sites for activated C3b.

Blotting, Western↗
PubMed1989

Detection of pseudorabies virus transcripts in trigeminal ganglia of latently infected swine.

Two pseudorabies virus (PRV) poly(A)+ RNAs, 2.0 and 0.95 kilobases, were detected in the trigeminal ganglia of latently infected pigs. These RNAs were partially colinear at the 3' end. They were located in the BamHI J fragment (0.706 to 0.737 map units), 3' of the PRV immediate-early gene. A potential polyadenylation signal was also identified in BamHI-J. The direction of transcription of the latency-associated RNAs was antiparallel (i.e., opposite in polarity) to that of the PRV immediate-early mRNA.

Animals↗
PubMed1989

Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.

Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement.

Animals↗
PubMed1989

Generalized beta 2-microglobulin deposition. A preamyloidosis disorder?

Generalized beta 2-microglobulin deposition in the tissues of a 64-year-old man with idiopathic end-stage renal disease was determined post mortem by the use of immunoperoxidase and radial immunodiffusion techniques. He developed progressive organ failure secondary to beta 2-microglobulin deposition, requiring dialysis for the last two years of his life. His immediate cause of death was severe bronchopneumonia. The extensive tissular deposits were shown to be congophilic but not birefringent by alkaline Congo red stains. Immunochemical studies showed that the deposits were beta 2-microglobulin-positive but AA amyloid-, P-component-, prealbumin-, and kappa and lambda light chain-negative. We suggest that this patient had a primary beta 2-microglobulin dyscrasia in which beta 2-microglobulin deposited in tissues but did not undergo complete amyloidogenic change.

Amyloidosis↗
PubMed1988

Fine mapping of the immediate-early gene of the Indiana-Funkhauser strain of pseudorabies virus.

The immediate-early gene transcript of pseudorabies virus was found to be 5.6 kilobases and colinear with the DNA genome. Transcription initiation started in the BamHI E fragment, 45 nucleotides from the BamHI-E/BamHI-I junction. The first AUG codon was located in BamHI-I, 260 nucleotides from the mRNA initiation site, and a potential TGA termination codon was located in BamHI-J, 161 nucleotides from the BamHI-I/BamHI-J junction. The AATAAA polyadenylation signal was 30 bases from the stop codon, while the actual polyadenylation site was 18 bases further downstream.

Animals↗
PubMed1987

The role of thromboxane in cuprophan-induced pulmonary hypertension.

Previous studies demonstrated that acute infusion of cuprophan activated plasma into experimental animals produce cardiopulmonary changes which included severe pulmonary hypertension. It was further suggested that these changes were mediated by complement activation products. The current study examined the role of arachidonic acid metabolites in the pathogenesis of cuprophan-induced pulmonary hypertension in the swine. Plasma thromboxane concentrations and pulmonary arterial pressure rose concomitantly with cuprophan-activated plasma infusion; both could be inhibited by the specific thromboxane synthetase inhibitor, OKY1581. Likewise, this inhibitor also blocked the increment in plasma thromboxane concentrations and pulmonary arterial pressure induced by zymosan-activated plasma. In vitro incubation of cuprophan-activated plasma with porcine lung fragments produced significantly higher thromboxane concentrations in the medium than incubation with other porcine tissues examined. It is postulated that the complement activation products formed in the plasma during cuprophan exposure subsequently stimulated release of thromboxane from the lungs and other tissues upon infusion of the plasma into animals. The thromboxane, in turn, triggers the pulmonary hypertension.

Animals↗
PubMed1987

Animal models to study the cardiopulmonary effects of artificial kidney membranes.

Some adverse reactions occurring during hemodialysis have been suggested to be caused by the bioincompatibility of dialyzer membranes. Experimental sheep and swine models have been developed to study the biological effects of these membranes. Infusion of cuprophane-activated plasma into the animals produces drastic hematologic and cardiopulmonary alterations. Available data suggest that these alterations are mediated by complement activation products and arachidonic acid metabolites. The consistent and sensitive nature of these models makes them useful tools to further study the interactions between the blood elements and artificial kidney membrane surfaces.

Anaphylatoxins↗
PubMed1986

Compartmental distribution of complement activation products in artificial kidneys.

The compartmental distribution of the human anaphylatoxins C3a and C5a has been defined during simulated hemodialysis performed with various types of hemodialyzers. New cuprophan hollow fiber dialyzers were found to activate human complement very readily in vitro, while re-used cuprophan dialyzers displayed only modest complement activating potential. The C3a and C5a antigens, formed as a result of complement activation in these dialyzers, accumulated predominantly in the blood path and were not adsorbed extensively on the membrane surface or transported into the dialysate compartment. Cellulose acetate membranes also produced complement activation in vitro, but to a lesser degree than new cuprophan hollow fibers. However, these membranes exhibited a significant capacity to bind the anaphylatoxins to their surface. Polyacrylonitrile membranes appeared to be unique in that they not only failed to activate complement significantly, but they rapidly adsorbed large quantities of C3a and C5a. These findings demonstrate that hemodialysis membranes may differ with regard to their complement activating potential as well as their ability to remove circulating anaphylatoxins from the blood path. Clinical measurements of anaphylatoxin production during hemodialysis reflect these dynamic events.

Complement Activation↗
PubMed1986

Cardiopulmonary effects of cuprophane-activated plasma in the swine.

Hemodialysis with cuprophane membrane is associated with complement activation and the formation of anaphylatoxins. Frequently, it is also complicated by various adverse reactions which include hypoxemia and hemodynamic changes. This study examined the cardiopulmonary effects of cuprophane membrane on experimental animals. To support the hypothesis that these effects were mediated by complement activation products, the effects of zymosan-activated plasma and C5adesArg challenge on the same variables were compared. We showed that intravenous infusion of autologous cuprophane-activated plasma into swine produced severe pulmonary hypertension, hypoxemia and leukopenia. In addition, mean systemic arterial pressure fluctuated and cardiac output fell. Infusion of zymosan-activated plasma produced similar results, suggesting that complement activation products are responsible for these alterations. Similar responses to porcine C5adesArg infusion suggested further that this polypeptide was the mediator. When swine were subjected to extracorporeal circulation using cuprophane membrane but without dialysis, acute pulmonary hypertension was seen preceding the onset of significant leukopenia. These data suggest that blood contact with cuprophane membrane produces both pulmonary and systemic hemodynamic changes, which are mediated by complement activation products. Furthermore, these products and/or other humoral factors, but not leukoagglutination, cause the pulmonary hypertension.

Animals↗
PubMed1985

Retinyl ester retention in chronic renal failure. Further evidence for a defect in chylomicron remnant metabolism.

The metabolic remnants of triglyceride-rich lipoproteins are atherogenic in man and experimental animals. Particles resembling lipoprotein remnants have been found in plasma from patients with chronic renal failure (CRF). In this study we took advantage of the observation that retinyl esters are transported only by lipoproteins that originate in the intestine, that is, by chylomicrons (CM) and their remnants. To investigate further remnant metabolism in CRF, plasma RE were measured by reverse-phase high performance liquid chromatography in 20 non-diabetic hemodialyzed patients with CRF and 20 hospitalized non-diabetic control subjects 12-15 h after the administration of retinyl ester, 25000 IU orally. Total plasma RE were increased 3-fold in the CRF patients (P less than 0.001). Quantitative analysis of retinoids and lipids in fractions separated by unit-gravity flotation and flocculation in 3% polyvinylpyrrolidone indicated that the plasma RE were not contained among intact CM. Mean plasma retinol in CRF was also elevated consistent with previous observations and the known role of the kidney in retinol-binding protein metabolism. Although postabsorptive RE concentration was correlated positively and significantly with plasma triglyceride concentration in both groups, RE were higher in CRF patients at comparable plasma triglyceride concentrations. These data support the proposal that atherogenic lipoprotein remnants accumulate in the plasma of patients with CRF.

Adult↗