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Biomedical subjects

K Wong

Publications and source records attributed to K Wong.

At least 199 records · Page 11Linked to original sources
PubMed1986

Effect of tobramycin on protein synthesis in 2-deoxystreptamine aminoglycoside-resistant clinical isolates of Haemophilus influenzae.

Clinical isolates of Haemophilus influenzae resistant to a broad range of 2-deoxystreptamine aminoglycosides (2-DAM) were studied. The gene responsible for resistance could be mobilized by transformation into a 2-DAM susceptible laboratory strain of H. influenzae, enabling isogenic comparisons. The transformants had the same resistance phenotype as the parental strains. There was close linkage between 2-DAM resistance and streptomycin resistance, a chromosomal marker, but weak linkage between 2-DAM and erythromycin resistance. Resistant transformants exhibited a decreased accumulation of gentamicin due to the absence of the rapid, energy-dependent phase of uptake. Resistance was not through metabolic inactivation of the antibiotic; no aminoglycoside-acetylating, -adenylylating, or -phosphorylating activity was detected in the wild-type strains or in the 2-DAM-resistant transformants. Protein synthesis in 2-DAM-susceptible H. influenzae strains increased in the presence of low (1 microgram/ml) and moderate (50 micrograms/ml) concentrations of tobramycin. With higher concentrations (100 and 500 micrograms/ml), protein synthesis was progressively inhibited. In contrast, protein synthesis in 2-DAM-resistant clinical isolates and transformants was inhibited by 1 microgram of tobramycin per ml, and inhibition increased with higher drug concentrations. Since the stimulating effect of low concentrations of tobramycin in susceptible H. influenzae strains is probably due to misreading, these findings suggest that 2-DAM-resistant strains of H. influenzae have reduced sensitivity to misreading, indicating that altered ribosomes are responsible for the resistance.

Aminoglycosides↗
PubMed1986

Comparison of 1-oleoyl-2-acetyl-glycerol and phorbol myristate acetate as secretagogues for human neutrophils.

Cellular responses induced in human neutrophils by the synthetic diacylglycerol, 1-oleoyl-2-acetyl-glycerol (OAG), paralleled those induced by phorbol myristate acetate (PMA). Like PMA, OAG caused the preferential release of enzymes from specific granules and promoted superoxide (O2-) generation. The efficacy of OAG was similar to that for PMA, but its potency was lower by four orders of magnitude. First derivative kinetic analysis showed that rates of O2- generation elicited by PMA decayed exponentially in a first order manner; the half life was found to be 21 +/- 6 min. Results obtained in studies carried out with high OAG concentrations were similar except that after 40 min, the rate of decay increased and became complex order. This difference was attributed to the greater susceptibility of OAG to metabolic alteration, and was reflected in the NADPH oxidase activity of granule rich membrane fractions (GRF) of cells stimulated for 90 min with PMA or OAG. It was found that the O2- generating activity of the PMA treated GRF was significantly greater than that for the OAG treated fraction. Current evidence indicates that cellular responses arise from direct activation of protein kinase C by PMA-OAG. The stability of this complex and the bypassing of normal regulatory constraints may account for the relative longevity of the PMA-OAG O2- respiratory burst.

Diglycerides↗
PubMed1986

Comparison of sonotubometry with tympanometry to assess eustachian tube function in adults.

Eustachian tube dysfunction is thought to be one of the most important factors in the development of middle ear effusions. Direct measurement of Eustachian tube opening is not widespread in clinical practice. Evaluation of a new, small and cheap sonotubometer was carried out on 50 volunteers. The results were compared with the measurement of Eustachian tube function by tympanometry and show a high degree of correlation (P less than 0.001).

Acoustic Impedance Tests↗
PubMed1986

The economic analysis of international migration: a generalization.

"This note examines and extends the following two propositions: that finite international factor movements are beneficial to the nationals of the destination country but detrimental to those left behind in the source country and that marginal movements do not have such welfare effects. Using some newly developed techniques, the propositions are found to be valid, irrespective of the number of goods and factors, if the economy starts from the autarky position. When only one factor can flow, the gain of the nationals (loss of those left behind) will be positively dependent upon the amount of inflow (outflow). However, if goods trade and/or factor flow are initially present, the propositions are in general not true." (SUMMARY IN FRE)

Demography↗
PubMed1986

Effects of gold compounds on leukotriene B4, leukotriene C4 and prostaglandin E2 production by polymorphonuclear leukocytes.

The effects of auranofin (AF) and sodium aurothiomalate (GSTM) on the production of specific arachidonic acid metabolites by chemotactic tripeptide activated polymorphonuclear leukocytes has been investigated using radioimmunoassay techniques. AF insignificantly enhanced the production of leukotrienes B4 and C4 at a concentration of 0.5 microgram Au/ml. However, at increasing concentrations, this drug suppressed the production of these metabolites in a dose dependent manner. In contrast, GSTM did not affect the production of either leukotriene at the concentrations tested. Of particular interest, prostaglandin E2 production was not affected by either gold compound. Both leukotrienes and prostaglandins are metabolized from arachidonic acid and are potent mediators of inflammation. The inhibition of leukotriene production may be another mechanism by which AF manifests its antiinflammatory effects in patients with rheumatoid arthritis.

Adult↗
PubMed1985

Calcium mobilization in fluoride activated human neutrophils.

Fluoride ion, at concentrations above 10 mM, was found to elicit a rise in intracellular calcium levels in neutrophils, as monitored by changes in Quin 2 fluorescence intensity. The calcium mobilization response was characterized by a lag period of 4 to 10 min. and a prolonged duration of action (greater than 20 min.). In contrast, the chemotactic peptide, formylmethionyl-leucyl-phenylalanine, induced a rise in intracellular calcium concentrations which peaked within 1 min. Preincubation of the cells with 1 microgram/ml pertussis toxin resulted in inhibition of the formylmethionyl-leucyl-phenylalanine induced response, but not that mediated by fluoride. Recent evidence suggests that the formylmethionyl-leucyl-phenylalanine receptor is coupled to phospholipase C and phosphoinositide degradation through a guanine nucleotide binding protein susceptible to inhibition by pertussis toxin. Present results suggest that fluoride ion may serve to activate this protein in a manner resistant to inhibition by pertussis toxin.

Adenylyl Cyclases↗
PubMed1985

Delta 5-desaturase activity in liver and brain microsomes during development of the pig.

Microsomes isolated from liver and brain tissue were assayed to examine transitions in metabolic capability to synthesize tetraenes and pentaenes by chain elongation-desaturation of C20:3(8,11,14) during the perinatal development of the pig. Rates of synthesis of tetraenes and pentaenes by chain elongation-desaturation of C20:3(8,11,14) were greatest in liver. During the latter half of gestation, the capability to synthesize tetraenes increased 7- or 23-fold on a per mg of microsomal protein basis for brain and liver respectively. Increase in the capacity to synthesize tetraenes from C20:3(8,11,14) suggests a significant transition in the activity of the delta 5-desaturase during the last half of gestation. These observations indicate that in liver and brain the capability to chain elongate-desaturate C18:2(9,12) to longer chain homologues increases significantly during early development as a function of transitions in the activity of the delta 5-desaturase.

Animals↗
PubMed1985

Synthesis of chain elongation-desaturation products of linoleic acid by liver and brain microsomes during development of the pig.

Microsomes isolated from liver and brain tissue were assayed to examine transitions in metabolic capability to synthesize chain elongation-desaturation products of C18:2(9,12) during the perinatal development of the pig. Microsomal synthesis of trienes, tetraenes and pentaenes was compared for fetal, neonatal and postnatal piglets. Rates of synthesis of tetraenes and pentaenes by chain elongation-desaturation of C18:2(9,12) were greatest in liver. During the later half of gestation, the capability to synthesize tetraenes increased 2-3-fold on a per mg of microsomal protein basis. Increase in the capacity to synthesize tetraenes suggests a significant transition in the activity of delta 5 desaturase during the last half of gestation. For brain, synthesis of C22:5(4,7,10,13,16) from C18:2(9,12) was greatest at term. These observations indicate that in liver and brain the capability to chain elongate-desaturate C18:2(9,12) to longer chain homologues increases significantly during early development. It is suggested that during gestation the activity of the delta 5 desaturase limits synthesis of C20 and C22 homologues of C18:2(9,12). The metabolic conversion of C20 and C22 fatty acids by chain elongation of C20:4(5,8,11,14) does not appear to limit the synthesis of very long chain homologues of linoleic acid in fetal liver or brain.

Animals↗
PubMed1985

Binding and internalization of heparin by vascular smooth muscle cells.

Previous work from our laboratory has demonstrated that heparin specifically inhibits the proliferation of vascular smooth muscle cells in vivo and in vitro. In this paper, we examine the binding and mode of internalization of heparin by smooth muscle cells. For these studies, radiolabeled and fluoresceinated (FITC) heparin probes were synthesized that retained their antiproliferative capacity. Binding of 3H-heparin to these cells occurs via specific, high-affinity binding sites (Kd = 10(-9) M, 100,000 binding sites per cell). Approximately 80% of the heparin bound to the cell surface was shed into the culture medium within 2 hr. The heparin that was left on the cell surface was internalized with biphasic kinetics. Approximately 50% of the bound material was internalized within 2 hr. After this initial rapid uptake, the rate slowed substantially, with the remaining heparin requiring 1-2 days to be internalized. Binding and uptake of FITC heparin was monitored using video image intensification fluorescence microscopy. When smooth muscle cells were exposed to FITC heparin at 4 degrees C, a diffuse surface staining pattern was observed. After warming the cells to 37 degrees C, intensely fluorescent vesicles were seen superimposed over the diffuse surface staining within 2 min. After 15 min at 37 degrees C, numerous large punctate vesicles were seen inside the cell. After 2 hr these vesicles had concentrated in the perinuclear region. This pattern of uptake, when considered along with the presence of specific, high-affinity binding sites and the initial rapid uptake of 3H-heparin, suggests that heparin enters smooth muscle cells by both receptor-mediated and other endocytic pathways.

Animals↗
PubMed1985

Slow exponential decay of rate of superoxide production in phorbol ester-activated human neutrophils.

Proper quantification of the superoxide (O2-) respiratory burst induced in human neutrophils is important for better understanding of the mechanism of action of stimulators and inhibitors. Reexamination of the reaction triggered by phorbol myristate acetate (PMA) indicated that it was a persistent process which lasted over 60 min. Plots of rates versus time show that rates of O2- release decayed logarithmically with a mean half-life (T1/2) of 21 +/- 6 min (SD), N = 12). Calculations of areas under curves indicate an average O2- yield of 217 +/- 99 nmol/10(6) cells. The inclusion of catalase in incubation mixtures did not alter the T1/2 or O2- yield, nor was the latter value affected by the quantitive scavenging of O2- by cytochrome c. Under certain conditions--the presence of excess dimethyl sulfoxide, the substitution of a less potent phorbol ester or activation of cells at high densities--the initial rate was either increased or decreased but a complementary alteration in the T1/2 resulted in little or no change in the total O2- yield. Retinol and retinol acetate decreased the initial rate, but retinoic acid enhanced it. By comparison, total O2- production was markedly reduced by all three agents with the following order of potency: retinoic acid greater than retinol greater than retinol acetate. In contrast, the serine protease inhibitor, TPCK, suppressed both the O2- yield and initial rate to a similar extent. On the basis of present observations, it is proposed that under normal conditions of PMA cellular activation, the logarithmic decay of the rate of O2- release was not due to autoinactivation of the O2--generating system, but rather to another factor, a possibility being the depletion of intracellular NADPH.

Humans↗
PubMed1985

Induction of IgA-specific suppressor activity in human T-lymphocyte cultures.

Cell-free supernatants of human circulating T-lymphocyte cultures incubated with secretory IgA (S-IgA) specifically suppressed both spontaneous IgA synthesis by B lymphocytes isolated from allergic individuals and pokeweek mitogen-induced IgA secretion by peripheral blood mononuclear cells. Cell-free supernatants of T-cell cultures incubated with IgE had no effect on IgA, IgG, or IgM synthesis. Hence, it is concluded that upon incubation with S-IgA, but not with another Ig class, T lymphocytes release IgA-specific suppressor factors.

Antibody Specificity↗
PubMed1985

Synthesis of chain elongated-desaturated fatty acids from palmitic acid by liver and brain microsomes during the development of the pig.

Rates of chain elongation-desaturation of C16:0 were compared for liver and brain microsomes in fetal, neonatal and postnatal piglets. Rates of chain elongation of C16:0 were greatest in liver in the postnatal period. For all developmental periods examined, the amount of chain elongated fatty acid of C20 or greater chain length exceeded the amount of C18 precursors synthesized from C16:0. These observations suggest that chain elongation of fatty acids occurs during the latter part of gestation at rates equivalent to that observed in the early postnatal period.

Aging↗
PubMed1985

Effect of the calcium ionophore A23187 on superoxide generation in phorbol ester stimulated human neutrophils.

The calcium ionophore, A23187, and the tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), interacted synergistically to elicit an accelerated superoxide production response in human neutrophils. The lag period preceding PMA-induced superoxide generation was decreased in a dose-dependent manner by A23187 at a concentration range from 1.0 X 10(-8) to 1.0 X 10(-5) M. Superoxide production rate, however, was subject to biphasic effects. While the rate was potentiated in a dose-dependent manner at A23187 concentrations below 1.0 X 10(-6) M, inhibitory influences became manifest at higher concentrations. Total superoxide production was subject to inhibitory effects, characterized by a mean inhibitory dose of 1.3 X 10(-6) M. The synergistic interaction of A23187 with PMA is consistent with a role for protein kinase C in neutrophil activation. Inhibition at high A23187 concentrations appeared to result from the effects of elevated intracellular Ca2+ levels on either NADPH oxidase itself, or some step in the transduction process linking protein kinase C to the oxidase complex.

Calcimycin↗
PubMed1984

The respiratory burst of human neutrophils treated with various stimulators in vitro is dampened by exogenous unsaturated fatty acids.

Cis-unsaturated free fatty acids (FFA) at concentrations between 10 and 30 microM suppressed the superoxide respiratory burst induced in human neutrophils by the chemotactic peptide, N-formylmethionyl-leucyl-phenylalanine (FMLP). Corresponding trans-isomers had a reduced efficacy while saturated FFA were inert. The effects of unsaturated FFA were maximally achieved after several min of preincubation with cells and reversed upon washing. Increased concentrations of Ca2+ in the medium also relieved the inhibition. Unsaturated FFA were equally effective in dampening the respiratory burst induced by fluoride ions but less so with bursts elicited by 9 nM phorbol myristate acetate (PMA). Moreover reactions triggered by higher concentrations (e.g., 100 nM) of PMA were resistant to the effects of FFA. Radioimmunoassays showed that unsaturated FFA directly elevated intracellular cyclic adenosine monophosphate (cAMP) by severalfold above basal levels. It is suggested that inhibition is brought about by unsaturated FFA perturbation of the neutrophil membrane structure, perhaps with an independent contribution from a cAMP-dependent mechanism.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1984

Immunocytochemical localization of urotensin I neurons in the caudal neurosecretory system of the white sucker (Catostomus commersoni).

The localization of urotensin I has been investigated in the caudal neurosecretory system of the white sucker (Catostomus commersoni). The peptide is present in all the cells of the system both large and small, in the large axons passing to the urophysis, and in fine beaded fibres not only within the urophysis but also in a fine plexus lateral to the large cells in the spinal cord proper. The possibility that the caudal neurosecretory system is not a functionally uniform system but rather a collection of dissimilar cells of different synaptic inputs with a common entity, urotensin I, is discussed. Moreover, the feasibility of a urotensin-I feedback loop is described.

Animals↗
PubMed1984

Selective media for the quantitation of bacteria in cystic fibrosis sputum.

We used selective media together with aerobic and anaerobic incubation for the quantitation of common pathogens in liquefied sputum from children with cystic fibrosis. The accuracy of the technique was verified by reconstruction studies in which laboratory strains with antibiotic-resistance markers were added to sputum from cystic fibrosis patients. Comparison of the numbers of bacteria found on quantitative culture of clinical specimens with the "predominant" organism found on routine culture yielded a poor correlation. When Pseudomonas aeruginosa was the most prevalent on routine culture, it was present in the highest numbers on quantitative culture (mean count = 10(8) cfu/g). However, large numbers of Haemophilus influenzae (mean count = 10(7) cfu/g), Staphylococcus aureus (mean count = 2 X 10(6) cfu/g), and streptococci (mean count = 2 X 10(6) cfu/g) were also present in these cultures. When S. aureus was the predominant organism, H. influenzae and P. aeruginosa were also present in similar numbers (c. 10(7) cfu/g). When H. influenzae was the predominant species on routine culture, the mean count was 7 X 10(6) cfu/g and P. aeruginosa was often completely absent. We conclude that the selective technique permits reliable enumeration of sputum bacteria, and offers a more accurate assessment of the microbial flora of sputum in cystic fibrosis than does simple plating of unhomogenised sputum.

Agar↗