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Biomedical subjects

K Cheung

Publications and source records attributed to K Cheung.

At least 73 records · Page 4Linked to original sources

Plant cardiac glycosides and digoxin Fab antibody.

The potential application of the Digoxin Fab antibody (Wellcome Digibind) in the clinical management of plant poisoning was investigated. The cardiac glycoside contents of various Australian plants were studied using immunoassay techniques. The cross-reactions of the Fab antibody and two digoxin assay antibodies against extracts of these plants were also studied. Results obtained indicated that the Digibind antibody cross-reacted with a wide range of glycosides contained in Australian plants and therefore could be of use in the treatment of life-threatening plant poisoning.

Adult↗

Vibratory acoustic stimulation and the flow velocity waveform in the fetal internal carotid artery.

Eleven healthy fetuses between 36 and 39 weeks of gestation were studied during the active sleep state to examine effects of a 5-s vibratory acoustic stimulus on the baseline fetal heart rate and flow velocity waveform in the fetal internal carotid artery. There was an immediate marked rise in baseline fetal heart rate with concomitant drop in pulsatility index in the flow velocity waveform of the fetal internal carotid artery, which persisted for at least 15 min after the stimulus. However, when the pulsatility index was standardized for a fetal heart rate of 140 beats/min this index remained virtually unaltered. These data suggest that in the healthy term fetus during active sleep state, a vibratory acoustic stimulus has no measurable effect on cerebral vascular resistance. Since virtually all reported studies on vibratory acoustic stimulation of the fetus were carried-out during the quiet sleep state, the data from the present study do not provide any information on the safety of this device when employed as a means of assessing of fetal well-being.

Acoustic Stimulation↗

Immunocytochemical localization of glycine in the retina of the turtle (Pseudemys scripta).

We have localized glycine-like immunoreactivity to provide new anatomical detail about glycinergic neurons in the turtle retina. A rabbit antiserum directed against a glycine/albumin conjugate was used with standard fluorescent and avidin-biotin labeling techniques. Some processes in the outer plexiform layer and many processes in the inner plexiform layer, numerous somata in the inner nuclear layer, and isolated somata in the ganglion cell layer were immunoreactive. The vast majority of labeled neurons were amacrine cells. One class of amacrine cells had well-labeled somata near the inner nuclear/inner plexiform layer border, which gave rise to thick primary processes that entered the inner plexiform layer and arborized near the border of strata 1 and 2 and in stratum 3. A second class of glycinergic neurons, consisting of putative interplexiform cells, was unique in that it gave rise to dendritic arborizations in both the outer plexiform layer and the inner plexiform layer. Some of the immunoreactive neurons in the ganglion cell layer were apparently displaced amacrine cells, while others were probably true ganglion cells because they gave rise to labeled axons, and many labeled axons were visible in the ganglion cell axon layer. These results suggested that glycine played an extensive role in the turtle retina, and that it was involved in many diverse synaptic interactions in both the outer plexiform layer and the inner plexiform layer.

Animals↗

Chemiluminescence of peripheral polymorphonuclear leukocytes from adult periodontitis patients.

Polymorphonuclear leukocytes (PMN's) constitute a primary host resistance factor against infection. This study investigated the chemiluminescent (CL) response of peripheral blood PMN's isolated from human subjects with adult periodontitis. 32 subjects were categorized on the basis of age and periodontal disease status into 4 equal groups--young healthy, young diseased, old healthy and old diseased. PMN CL was stimulated using heat-killed, serum-opsonized Fusobacterium nucleatum--a specific periodontopathic gram-negative anaerobe, and Escherichia coli as a gram-negative control organism. The results showed a statistically significant enhancement (p less than 0.05) in the CL response, which was cell associated, in the young diseased subjects. This was not seen in the old subjects (p greater than 0.05), suggesting that in periodontal disease in young subjects the peripheral blood PMNs may be in a metabolically activated state. There was nevertheless a degree of variability between individual subjects within each of the 4 clinical groups.

Adult↗

Detection of poisoning by plant-origin cardiac glycoside with the Abbott TDx analyzer.

Cardiac glycoside poisoning caused by ingestion of plant material is common in tropical and sub-tropical areas. In evaluating the use of the Abbott TDx Digoxin II assay to detect such cases of poisoning, we found it a rapid and convenient method for confirming the ingestion of glycosides from the plants Nerium oleander, Thevetia peruviana, and Adonis microcarpa, and from the toad Bufo marinus. Here we report some clinical cases illustrating our experience with the use of this assay, and describe results of cross-reactivity studies with compounds structurally similar to digoxin. Because of the competitive nature of the immunoassay as well as the complexity of the mixture of cross-reacting cardiac glycosides present in the plant material, the measured apparent digoxin concentration is not linearly related to the cardiac glycoside concentration.

Adolescent↗

Influence of T lymphocytes on hematopoiesis in a patient with T cell hypoplasia.

In this communication, we describe an unusual patient with a reported lifelong history of anemia. Investigation of the pathogenesis of this patient's bone marrow failure provided an interesting opportunity to determine the role of T cells in the regulation of human blood cell production. Phenotyping of the patient's mononuclear cells revealed severe T cell hypoplasia in both the peripheral blood and bone marrow. The patient's bone marrow was capable of producing 50-60% of the normal numbers of burst-forming units--erythroid (BFU-E) in the presence of optimal concentrations of erythropoietin, suggesting that marrow BFU-E formation is in part independent of T cells. Addition of small numbers of class I identical donor T cells enhanced BFU-E cloning efficiency to a level observed in normal controls. This enhancing effect was supplied by a T4+ (CD4) population of donor cells. The addition of donor T cells partially corrected the inability of patient marrow cells to produce megakaryocyte and mixed colonies. These studies suggest that prolonged T cell hypoplasia might deprive marrow progenitor and stem cells of a necessary enhancing effect that is required for sustained normal hematopoiesis. Such a T cell defect in rare instances may result in bone marrow failure.

Aged↗

The production of hydroxyl radical by human neutrophils stimulated by arachidonic acid--measurements by ESR spectroscopy.

Human neutrophils incubated with sodium arachidonate generated hydroxyl radicals. The radical formed an adduct with the spin trap 5', 5-dimethyl-l-pyrroline-N-oxide (DMPO) and was subsequently detected by electron spin resonance (ESR) spectroscopy. The ESR signal was inhibited by mannitol and superoxide dismutase but not by catalase. Removal of glucose from the reaction mixture or the presence of glucose metabolic inhibitors including 2-deoxy-D-glucose and 3-O-methyl-D-glucose did not affect the production of hydroxyl radical by the neutrophils. The ESR signal was, however, inhibited by the lipoxygenase inhibitors nordihydroguaiaretic acid and N-ethylmaleimide. The involvement of lipoxygenase in the production of hydroxyl radical was demonstrated by the trapping of the radical with DMPO in a reaction mixture of soybean lipoxygenase and arachidonic acid (AA). These findings support our previous postulation that the metabolism of AA via the lipoxygenase pathway is a source of hydroxyl radical in stimulated neutrophils.

3-O-Methylglucose↗

Stimulation of neutrophil respiratory burst and iodination reaction by opsonized microfilariae of Dirofilaria immitis.

It has been shown that the interaction of Dirofilaria immitis microfilariae (Mf) opsonized with sera from infected but amicrofilaraemic dogs (occult dogs) stimulated the respiratory burst and degranulation of neutrophils as measured by chemiluminescence and iodination. Sera from normal and microfilaraemic dogs gave either low level or non-significant reactions. Since the sera required were also those required for neutrophil-mediated cytotoxicity to D. immitis Mf in vitro, the results suggested that the products of oxygen reduction as well as the myeloperoxidase system could be involved in the killing of Mf by neutrophils. However, whether these pathways have a major role to play in neutrophil-mediated cytotoxicity to Mf is uncertain, as various chemical and enzymatic inhibitors of the products of the respiratory burst were unable to prevent or reduce cytotoxicity. Azide, which is a known inhibitor of the iodination reaction, also failed to reduce cytotoxicity.

Animals↗

Luminol-dependent chemiluminescence produced by neutrophils stimulated by immune complexes.

The origin of luminol-dependent chemiluminescence (CL) in neutrophils stimulated by immune complexes (IC) was investigated. It was found that CL induced by soluble IC and aggregated human gamma globulin (AHG) was glucose-independent, while insoluble IC-induced CL was diminished in the absence of glucose. AHG-induced CL was not inhibited by superoxide dismutase, catalase or 2,5-dimethyl furan, but was suppressed in the presence of phenol, sodium benzoate, sodium formate and mannitol. The CL was also inhibited by inhibitors of arachidonic acid (AA) metabolism including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin and aspirin, and by prostaglandins E1 and E2, theophylline and dibutyryl cyclic AMP. Luminol-dependent CL was also studied in cell-free systems including AA plus soybean lipoxygenase, hydroperoxyeicosatetraenoic acid plus peroxidase and xanthine oxidase plus xanthine. Our results indicate that, in neutrophils exposed to soluble IC and AHG, CL is produced and this is closely linked to the formation of free radicals during the metabolism of AA. The radical(s) involved is likely to include the hydroxyl radical. In neutrophils stimulated by large aggregates of IC or micro-organisms, superoxide anion, H2O2 and singlet oxygen are also produced as a result of activation of NAD(P)H oxidase. These oxygen species function as oxidizing agents for AA metabolism and amplify the production of hydroxyl radical along the lipoxygenase (and possibly cyclooxygenase) pathway(s).

Antigen-Antibody Complex↗

The measurement of the oxygen tension of lymph in conscious sheep.

A method is described for continuously measuring the PO2 of lymph in conscious sheep. An indwelling polarographic electrode inserted into a plastic cannula has been used to measure the PO2 in efferent popliteal lymph close to the point at which the lymph leaves the node. The mean PO2 of popliteal lymph in normal sheep was found to be 46.6 +/- 5.3 mm Hg, equivalent to 7.1 +/- 0.8% O2. Following antigenic challenge with killed Salmonella bacteria, the PO2 of the lymph changed significantly. These changes were related to the cellular response in the lymph and in the node. The PO2 values were maximum in the lymph 8 h after the injection of antigen during the 'shut-down' period and minimum at around 80 h when the blast cell response was at its height. These in vivo findings suggest that in vitro studies on sheep lymphocytes should be done with gas mixtures containing 7% O2.

Animals↗

The respiration and energy metabolism of sheep lymphocytes.

The respiration characteristics and energy metabolism of sheep lymphocytes collected from the popliteal lymph before and after antigenic challenge with Salmonella organisms have been studied at various O2 tensions. The O2 consumption of sheep lymphocytes could be related to the PO2 of the medium by the Michaelis-Menten equation. In resting lymphocytes, Vmax (mean +/- S.D.) was 1.70 +/- 0.23 mumoles/h/2 X 10(8) cells), critical O2 concentration [( O2]crit) was 2.00 +/- 0.20 microM and Km was 0.46 +/- 0.11 microM. Significant changes occurred in the respiration characteristics of these cells following antigenic challenge of the node. Both Vmax and Km reached maxima when the blast cell response in the lymph was at its peak. [O2]crit, however, did not change significantly over an immune response. Lymphocytes collected before antigenic challenge had mean rates of glucose uptake of 0.97 +/- 0.29 mumoles/h/2 X 10(8) cells and lactate production of 1.31 +/- 0.37 mumoles/h/2 X 10(8) cells. During the height of immune responses to Salmonella, lymphocytes showed an enhanced glucose uptake, lactate production and C-1- and C-6-labelled glucose metabolism. The rates of energy metabolism of sheep lymphocytes varied with changes in the PO2 of the gas phase from 21% to 0% O2. The rates of glucose uptake and lactate production increased while the rates of 14CO2 production from C-1- and C-6-labelled glucose decreased as the PO2 decreased.

Animals↗

Mixed lymphocyte culture responses. Lack of correlation with cadaveric renal allograft survival and blood transfusions.

One-way and two-way mixed lymphocyte reactions (MLRs) between 65 cadaveric renal allograft recipients (R) and their specific-donor (D) and pooled third-party (P) cells were measured using a 5-day assay. There was no correlation between the results expressed as stimulation index, absolute counts, or the relative response and graft survival in transfused allograft recipients. Nontransfused recipients whose first graft failed had significantly higher responses to P, but not D, than those with successful grafts. The one-way MLRs to P of 61 cadaveric graft recipients and 52 potential recipients were measured. No correlation was found between the magnitude of the response and the number of transfusions, time since the last transfusion, or peak cytotoxic antibody production. Our results suggest that a standard 5-day MLR has little clinical value in predicting the results of cadaveric transplantation in HLA-A,B-mismatched recipient-donor pairs. We could not demonstrate any overall effect of transfusions on the MLR, suggesting that this may not be the mechanism by which transfusions exert their effect on graft survival.

Adolescent↗

The interaction of lymphocyte surface-bound immune complexes and neutrophils.

Neutrophils can be stimulated directly by a variety of stimulants resulting in the production of highly reactive oxygen derivatives. Included in these stimulants are peripheral blood lymphocytes with bovine serum albumin-anti-bovine serum albumin immune complexes (BSA-IC) or aggregated gamma-globulin (AHG) bound to their surface receptors. Through the use of chemiluminescence (CL) studies, we found that B lymphocytes preincubated with AHG stimulated neutrophils to a much greater extent than similarly preincubated T lymphocytes. Preincubated Raji cells (a B lymphoblastoid cell line) were also capable of stimulating neutrophils. We further demonstrated that after periods of mixed incubation with neutrophils, lymphocytes with surface-bound AHG did show an abnormal proliferative response to pokeweed mitogen (PWM), but not to phytohemagglutinin (PHA). This was not due to loss of cell viability, as judged by chromium release cytotoxicity assays and trypan blue exclusion, or to neutrophil enzyme release. The data suggest that neutrophils, stimulated with lymphocyte surface-bound immune complexes, are capable of producing an environment of in vitro oxidant stress. This stress, although not great enough to cause a significant decrease in lymphocyte viability, can cause impaired lymphocyte function. Physiologically, this may relate in the long term to immunologic malfunction observed in patients with high levels of circulating immune complexes.

Antibodies, Anti-Idiotypic↗