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Biomedical subjects

K Wong

Publications and source records attributed to K Wong.

At least 217 records · Page 12Linked to original sources
PubMed1984

In vitro synthesis of IgE by human lymphocytes. III. IgE-potentiating activity of culture supernatants from Epstein-Barr virus (EBV) transformed B cells.

Seven Epstein--Barr virus (EBV)-transformed B cell lines were derived from circulating lymphocytes of two atopic and two non-atopic individuals, two preparations of cord blood lymphocytes and one tonsillar lymphocyte preparation. All the cell lines contained a significant proportion of cells expressing Fc epsilon R as detected by rosette formation with IgE-coated bovine erythrocytes (E-IgE) and by flow cytometry using IgE-linked to fluorescent microspheres. None of the cell lines displayed FcR for IgA, IgM or IgG. The cell-free supernatants (CFS) of EBV-transformed cells contained IgE-binding factors (IgE-BFs) detected by their ability to inhibit the binding to RPMI 8866 cells of either E-IgE or IgE-linked to microspheres. Whereas these CFS enhanced the synthesis of IgE and suppressed the synthesis of IgG by purified B lymphocytes isolated from the blood of allergic donors and cultured in the absence of stimulant, their effect on the synthesis of IgA or IgM was not predictable. CFS significantly enhanced the secretion of IgE by the U266 myeloma cell line without interfering with secretion of IgM, IgG or IgA by EBV-transformed cells. These data are in accord with similar properties of RPMI 8866 cells and suggest that B lymphocytes might play a regulating role in the IgE synthesis.

B-Lymphocytes↗
PubMed1984

In vitro synthesis of IgE by human lymphocytes. II. Enhancement of the spontaneous IgE synthesis by IgE-binding factors secreted by RPMI 8866 lymphoblastoid B cells.

RPMI 8866 lymphoblastoid cells, known to express surface Fc epsilon R, were tested for their ability to regulate the in vitro synthesis of human IgE. Cell-free supernatants (CFS) of RPMI 8866 cells enhanced in a dose-dependent fashion the spontaneous IgE synthesis by B cells of allergic individuals. For maximum activity the CFS had to be added during the first 3 days of culture. CFS did not significantly alter the spontaneous synthesis of IgM or IgG, but they suppressed IgA synthesis both in B cell cultures and in pokeweed mitogen-stimulated peripheral blood mononuclear cells cultures. Cyclosporin A did not suppress either the spontaneous Ig production by B cells nor the IgE-potentiating activity of CFS. The enhancing activity of CFS was related to its content in IgE binding factors (IgE-BFs); these factors were detected by their ability to inhibit the rosetting of RPMI 8866 cells with IgE-coated erythrocytes (E-IgE). Both the IgE-BFs and the IgE-potentiating activity of the supernatants of RPMI 8866 cell cultures could be removed by absorption with IgE-Sepharose, from which they could subsequently be eluted with glycine-HCl buffer. IgE-BFs were identified as glycoproteins on the basis of their sensitivity to trypsin and to neuraminidase. By filtration of the RPMI 8866 cell supernatants through a Sephadex G75 column, IgE-binding activity was found to be associated with two fractions with molecular sizes in the range of 10,000-15,000 and 30,000-40,000. The IgA-suppressing activity of the RPMI 8866 culture filtrates could be absorbed with sIgA-Sepharose from which it was subsequently recovered by elution with glycine-HCl buffer. Most unexpectedly, sIgA-Sepharose also removed IgE-BFs and IgE-potentiating activity from the RPMI 8866 supernatants; both could be recovered by subsequent elution from sIgA-Sepharose with gycline-HCl buffer. These data are provisionally interpreted as indicating that the IgE-BFs secreted by RPMI 8866 cells had affinity for both IgE and sIgA and that they exerted a reciprocal effect on the in vitro synthesis of IgE and IgA.

B-Lymphocytes↗
PubMed1984

In vitro synthesis of IgE by human lymphocytes. I. The spontaneous secretion of IgE by B lymphocytes from allergic individuals: a model to investigate the regulation of human IgE synthesis.

In view of the controversial data in the literature regarding the in vitro IgE synthesis by human lymphocytes, the conditions for culture of lymphocytes and the methodology for measurement of the IgE produced are described in detail. In the absence of any added mitogen, enriched B cell preparations derived from 70% of allergic donors actively secreted 100 to 3200 pg/ml of IgE after culture for 7 days, at which time the cell viability was higher than 85%. In comparable B cell cultures derived from non-allergic donors, only trace amounts of de novo synthesized IgE were detected in 20% of the cases. All B cell cultures actively secreted IgG, IgA, IgM and there was no apparent relationship between the secretion of IgE and that of the other classes of Ig. By contrast, the synthesis of IgE by unfractionated peripheral blood mononuclear cells of allergic individuals, which were stimulated with pokeweed mitogen (PWM) under several experimental conditions, was not consistently reproducible, i.e. the spontaneous synthesis of IgE in such cultures was either suppressed or enhanced by PWM. The most important finding was that the secretion of IgE was selectively enhanced by supplementing the B cell cultures with cell-free supernatants (CFS) of cultures of neonatal lymphocytes which had been preincubated with 10 micrograms/ml IgE. It is, therefore, concluded that B cell cultures from allergic individuals constitute an appropriate model for investigations of the mechanisms underlying the regulation of human IgE synthesis.

Adult↗
PubMed1984

Characterization of endotoxin-induced C5-derived chemotactic activity in aqueous humor.

Although a cellular exudate characterizes acute anterior uveitis, few studies have sought to identify the chemoattractant(s) contributing to this phenomenon. As a model of acute ocular inflammation, the authors have injected rabbits intravenously with endotoxin (Salmonella typhimurium LPS, 2.5 micrograms/kg). In a Boyden chamber assay, aqueous humor drawn 3 hr after LPS (post-LPS aqueous) exhibited chemotactic activity for purified rabbit granulocytes (PMN). "Checkerboard" analysis indicated that chemotaxis, rather than protein-induced chemokinesis, primarily accounted for PMN migration. Aqueous from normal rabbits demonstrated no chemotactic activity. Chemotactic activity was maximal at 3 hr post-LPS (versus 1 or 5 hr). PMN migration exhibited a direct correlation with the concentration of aqueous tested (0.5-5%). Several observations indicated that this chemotactic activity is complement (C5)-derived. It is inhibited by antibodies to C5 but not affected by antibodies to C3. Similar to rabbit C5a, chemotactic activity in post-LPS aqueous was heat stable at 56 degrees C X 30 min, attracted both human and rabbit PMN at similar concentrations and induced release of beta glucuronidase from PMN. In addition, prior incubation of rabbit PMN with partially purified C5a (densensitization) specifically inhibited chemotactic responses to both C5a and post-LPS aqueous without inhibiting responses to another chemoattractant, n-formyl-methionyl-leucyl-phenylalanine. Finally, chemotactic activity from post-LPS aqueous could be recovered from a Sephadex G75 column and eluted similarly to chemotactic activity in zymosan activated rabbit serum or 13,700 D molecular weight marker. The presence of complement-derived chemotactic activity in this model should not be construed as evidence that this activity contributes to the pathogenesis of endotoxin-induced inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effects of gold compounds on the function of phagocytic cells. II. Inhibition of superoxide radical generation by tripeptide-activated polymorphonuclear leukocytes.

The effect of sodium aurothiomalate and triethylphosphine gold on the generation of superoxide radicals by chemotactic tripeptide-activated polymorphonuclear leukocytes has been investigated using a cytochrome C reduction technique. Neither gold compound inhibited the binding of the tripeptide to cells. Sodium aurothiomalate in concentrations ranging from 1 to 100 micrograms/ml produced mild, nonsignificant inhibition of the generation of superoxide radicals. In contrast, triethylphosphine gold at a concentration of 0.25 microgram/ml was associated with a mild enhancement of superoxide radical production, but the enhancement was not statistically significant. At concentrations of 1.25 micrograms/ml and above, there was a profound inhibition of superoxide radical production by these activated cells. Since the products of the respiratory burst, including superoxide, are thought to be inflammatory mediators, it is postulated that the inhibition of superoxide radical generation by gold compounds may be another mechanism by which the compounds modulate their antiinflammatory effects in patients with rheumatoid disease.

Binding Sites↗
PubMed1983

High-pressure liquid chromatographic quantitation of azlocillin.

We describe a rapid, precise, and simple procedure for the quantitation of azlocillin in serum and in aqueous solutions by high-pressure, reverse-phase liquid chromatography. This method uses a single precipitation step, detection by dual-wavelength monitoring (220 and 254 nm), and quantitation by comparison with an internal standard. The 10-micron C18 muBondapak column was eluted with 45% (vol/vol) methanol-65% (vol/vol) phosphate buffer. The precision was 4.2 and 5.6% at 50 and 10 micrograms/ml, respectively. The assay was linear up to concentrations of 100 micrograms/ml, with recoveries of 90.4 to 110.5% from serum. The assay was sensitive to 0.4 micrograms of azlocillin per ml. The short turnover time (14 min) and small serum sample size (20 microliters) make the assay ideal for therapeutic drug monitoring and clinical pharmacokinetic studies.

Azlocillin↗
PubMed1983

The interactive effects of fluoride and N-formyl-L-methionyl-L-leucyl-L-phenylalanine on superoxide production and cAMP levels in human neutrophils.

The kinetics of superoxide (O2-) production and intracellular cAMP levels were monitored in human neutrophils incubated in vitro with sodium fluoride and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). F- activation of both the O2- -generating system, NAD(P)H oxidase, and adenylate cyclase was characterized by a prolonged lag period of 8 to 10 min at 37 degrees C. Adenylate cyclase agonists or cAMP analogues which inhibited FMLP-induced O2- bursts did not affect O2- production of F- -activated cells. Prior treatment of cells with F- suppressed the short rapid burst elicited by FMLP but not the binding of the tripeptide. FMLP reciprocally decreased the lag period of the F- -induced burst by 40 to 50% and, in the case of cells incubated at temperatures below 37 degrees C, increased the rate of O2- production. A similar potentiating effect of FMLP on F- -induced elevation of intracellular cAMP levels was observed.

Adenylyl Cyclases↗
PubMed1983

Superoxide production in neutrophils of patients with rheumatoid arthritis and Felty's syndrome.

The production of superoxide by N-formylmethionyl-leucyl-phenylalanine activated neutrophils was measured prospectively with a ferricytochrome C reduction assay in 33 normals, 33 patients with rheumatoid arthritis and 9 patients with Felty's syndrome. Both the rate and quantity of superoxide production were significantly lower in patients with Felty's syndrome when compared to the other 2 groups. This finding suggests a possible additional factor in the increased propensity of these patients to develop infections.

Arthritis, Rheumatoid↗
PubMed1981

Visual loss as the initial symptom of systemic lupus erythematosus.

A 42-year-old woman had severe, bilateral visual loss and the initial symptom of systemic lupus erythematosus. Fundus photographs and fluorescein angiograms demonstrated an inflammatory process and severe ischemia. Vision in the less severely affected eye markedly improved after systemic and retrobulbar administrations of corticosteroids.

Adrenal Cortex Hormones↗
PubMed1981

Acute effects of acebutolol on cardiovascular function in man.

1 The acute cardiovascular effects of acebutolol were measured at constant paced heart rate in thirteen patients investigated for possible coronary artery disease, six of whom showed significant coronary stenosis with regional myocardial dysfunction, seven of whom proved normal. Acebutolol 0.75 mg/kg i.v. was given to three patients with coronary artery disease and three normals, and 1 mg/kg i.v. to the other patients.2 Measurements were made of cardiac output, left ventricular and arterial pressures, and left ventricular angiography. Isovolumic and ejection phase parameters of left ventricular function, and systemic vascular resistance were derived. Plasma levels of acebutolol were measured. 3 The acute effects of acebutolol were a slight fall in cardiac output, LV dp/dt and dP/dt/P. There was no change in LV or arterial pressures, no consistent change in LVEDP or EDV, and no consistent change in ejection fraction or mean VCF. These changes imply a small negative inotropic effect, more marked at the higher dose. 4 The effects of acebutolol differed in patients with ischaemic heart disease compared with normals in that LVEDP and EDV increased, mean VCF decreased and cardiac output was lowered more. 5 These data are consistent with myocardial and vascular effects of beta-adrenoceptor blockade more marked at the higher dose and more marked in patients with ischaemic heart disease.

Acebutolol↗
PubMed1981

The components of synaptic potentials evoked in cat spinal motoneurones by impulses in single group Ia afferents.

1. Excitatory post-synaptic potentials (e.p.s.p.s) were evoked in cat spinal motoneurones by impulses in single group Ia afferent fibres. The probability density of the fluctuations in peak amplitude of each e.p.s.p. was calculated from the recorded peak amplitude and the probability density of the recording noise. 2. Most e.p.s.p.s fluctuated between different components (i.e. individual e.p.s.p.s of a particular discrete amplitude) with peak amplitudes which were integer multiples of the increment between successive components. The average peak amplitude of this incremental e.p.s.p. was about 90 microV for e.p.s.p.s generated at or near the soma. 3. In general, the probability density of the peak amplitude could not be described using Poisson or binomial distributions. 4. For many e.p.s.p.s the complete time course of each component could be calculated. There was no variability in the amplitude of these components nor in their latency of onset. For some e.p.s.p.s there were differences in the latency and time course of the components. 5. The increments between successive components of e.p.s.p. generated proximally were no larger (at the soma) than the corresponding increments for e.p.s.p.s generated at more distal dendritic sites. 6. These results and those from subsequent papers (Jack, Redman & Wong, 1981; Hirst, Redman & Wong, 1981) reinforce earlier suggestions that each bouton behaves in an all-or-nothing manner with respect to post-synaptic effect, and the probability of failure varies at different boutons arising from the same afferent.

Animals↗
PubMed1981

Post-tetanic potentiation and facilitation of synaptic potentials evoked in cat spinal motoneurones.

1. Excitatory post-synaptic potentials (e.p.s.p.s) were evoked in spinal alpha-motoneurones of the cat by impulses in single group Ia nerve fibres. 2. The average peak amplitude of some of these e.p.s.p.s was increased by a conditioning tetanus. The maximum increase observed was 54% of the control amplitude. 3. The average peak amplitude of some e.p.s.p.s was increased by a single conditioning stimulus which preceded the test stimulus by 1 or 2 msec. The maximum increase observed was 28% of the control amplitude. 4. The ability of e.p.s.p.s to potentiate following a tetanus was correlated with their ability to be facilitated by a single conditioning stimulus. 5. If an e.p.s.p. could be facilitated prior to a tetanus, the amount of facilitation was reduced after the tetanus, with all facilitation being abolished when post-tetanic potentiation was maximal. 6. The fluctuations of an e.p.s.p. were analysed before and after a tetanus. The peak amplitudes that an e.p.s.p. fluctuated between while potentiated did not gradually diminish as the effect of the tetanus disappeared. Post-tetanic potentiation, when it occurred, was accompanied by a decrease in the probability of occurrence of components with smaller peak amplitudes and an increase in the probability of occurrence of components with larger peak amplitudes. 7. These results are consistent with the suggestion that the magnitude of the synaptic potential generated at a single bouton does not vary from trial to trial (Jack, Redman & Wong, 1981a). Nor does the amplitude of this potential vary following a single conditioning stimulus or a tetanus. Post-tetanic potentiation and facilitation result from a decrease in the probability of failure to release transmitter following the conditioning stimuli.

Animals↗
PubMed1981

Modifications to synaptic transmission at group Ia synapses on cat spinal motoneurones by 4-aminopyridine.

1. The average amplitude of e.p.s.p.s evoked in cat spinal motoneurones by impulses in single group Ia afferents usually increased following the intravenous injection of 4-aminopyridine (4-AP). Most of this increase occurred over the first 30 min following injection of 4-AP. 2. The increase in the average amplitude following 4-AP occurred by a reduction in the probability of occurrence of component e.p.s.p.s with smaller peak amplitudes, and an increase in the probability of occurrence of component e.p.s.p.s with larger peak amplitudes. There was no evidence that the discrete amplitudes of components after 4-AP were a result of graded increases of the discrete amplitudes before 4-AP. 3. The interpretation suggested for these results is that each component e.p.s.p. is generated by transmission at a different combination of boutons. At each of these boutons sufficient transmitter is released to saturate all available receptors. The effect of 4-AP is to decrease the probability of failure to release transmitter at each bouton, including some boutons which, before 4-AP, did not release transmitter.

4-Aminopyridine↗
PubMed1981

Inhibition of the n-formylmethionyl-leucyl-phenylalanine induced respiratory burst in human neutrophils by adrenergic agonists and prostaglandins of the E series.

Exogenous prostaglandins E1 and E2 and L-isoproterenol potently inhibited the production of superoxide anions by human neutrophils activated in vitro by n-formylmethionyl-leucyl-phenylalanine (FMLP). An estimated ID50 of 50 nM was found for all three agents while L-epinephrine and prostaglandin F2 alpha were 10 and 100 fold, respectively, less active. Inhibition occurred whether these agents were added before, together with, or after the addition of the tripeptide to cell suspensions. Cells treated with dibutyryl adenosine 3',5'-monophosphate also expressed reduced rates of superoxide synthesis thus suggesting that the hormonal inhibitors acted indirectly by stimulating membrane bound adenylate cyclase.

Humans↗
PubMed1981

Sperm shape abnormalities in carbaryl-exposed employees.

Semen was collected from 50 men occupationally exposed to carbaryl (1-naphthyl methyl carbamate) in a produciton plant for durations of 1 to 18 years and compared to semen from a control group of 34 unexposed, newly-hired workers. Employment, fertility, health, personal data, and blood samples were collected for each individual. Semen samples were analyzed for changes in sperm count, morphology, and frequency of sperm carrying double flourescent bodies (YFF). As a group, the exposed workers showed a significantly higher proportion of sperm with abnormal head shapes than did the control group (p < 0.005). Age, smoking habits, and medical problems did not appear to affect this result. This finding appears to be limited to men working in the carbaryl production area at the time of sampling. Sperm count and YFF did not show similar differences, which may be because they are known to be statistically less sensitive to small changes. Formerly exposed workers (away from carbaryl for an average of 6.3 years) showed a marginally significant elevation in sperm abnormalities compared to controls (p < .05, one-tailed statistical analyses) suggesting that the increase in abnormal morphology may not be reversible. However, the question of reversibility is sensitive to confounding factors and small sample sizes and, therefore, requires further study. With these data a definitive link between carbaryl exposure and human seminal defects cannot be established. Although a distinct effect on sperm morphology was seen in the exposed group, the increases in sperm shape abnormalities were not related to exposure dose (estimated by number of years on the job or job classification during the year prior to semen collection). Inexplicably, the increases in sperm abnormalities were seen primarily in currently exposed men who had worked with carbaryl for less than approximately 6 years. These findings suggest the need for further study since other workplace-related factor(s) may be responsible for the elevated sperm abnormalities seen in this study.

Adult↗