Search PubMed⌕ Search

Biomedical subjects

H Chan

Publications and source records attributed to H Chan.

At least 127 records · Page 7Linked to original sources

Activation of distinct protein kinase C isozymes by phorbol esters: correlation with induction of interleukin 1 beta gene expression.

Treatment of human promyelocytic leukemia cells U937 with phorbol 12-myristate 13-acetate (TPA) induces them to differentiate into monocytic cells [Harris, P., & Ralph, P. (1985) J. Leukocyte Biol. 37, 407-422]. Here we investigated the effects of TPA on interleukin 1 gene expression and the possible role of protein kinase C (PKC) in this process. Addition of TPA to serum-starved U937 cells induced the expression of the interleukin 1 beta (IL-1 beta) gene. This effect was apparent as early as 2 h and peaked at 24 h in the presence of 5 X 10(-8) M TPA. Higher concentrations of TPA, which partially or totally depleted protein kinase C levels in the cells (10(-9)-2 X 10(-5) M), had an inhibitory effect on IL-1 beta mRNA expression. Cell-permeable 1,2-dioctanoyl-sn-glycerol (diC8), a diacylglycerol that activates PKC in intact cells and cell-free systems, did not mimic the effect of TPA on the IL-1 beta mRNA induction. To determine the protein kinase C isozymes present in the control and TPA- (5 X 10(-8) M) treated U937 cells, we prepared antipeptide antibodies that specifically recognize the alpha, beta, and gamma isoforms of protein kinase C in rat brain cytosol and U937 cell extracts. In "control" U937 cells, 30% of PKC alpha was particulate, and PKC beta was cytosolic, while there was no detectable PKC gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

[Serial determination of anthracycline poisoning in children].

Dose-related cardiotoxicity limits enthracycline administration in patients with solid tumours or leukaemia. Many patients (70%) would probably benefit by receiving more than a total accumulative dose of 500 mg/m2. As a measure of myocardial function the left ventricular ejection fractions (EF) were determined from serial radionuclide angiograms in 62 children who had at least 3 studies (mean age 8.4 +/- 5.4 years). Seven patients who had clinical evidence of cardiac involvement and/or a marked decline in their EF underwent endmyocardial biopsy (9 x). The EF declined progressively from 63 +/- 7% prior to chemotherapy to 60 +/- 5%, 58 +/- 7% and 54 +/- 7% after low, medium and high-dose anthracycline, respectively in the non-biopsied children vs 58 +/- 4%, 54 +/- 7% and 48 +/- 4% in the biopsied patients. Anthracycline dosage was 129 +/- 42, 307 +/- 68 and 471 +/- 61 mg/m2 and 103 +/- 64, 303 +/- 73 and 536 +/- 93 mg/m2, respectively. The biopsies were obtained at a mean anthracycline dose of 408 mg/m2 when the EF was 46 +/- 5%, and graded according to the modified Billingham score; grade 1 (6 x), 1.5 (2 x) and 2.5 (1 x). A decline in the EF was seen in 89% of our patients throughout their chemotherapy course, with a statistical significance of p less than 0.02 in the biopsied patients after medium dose therapy which was not seen in the non-biopsied children until they were receiving anthracyclines.

Biopsy↗

Histamine and leukotrienes release in bronchoalveolar fluid during plicatic acid-induced bronchoconstriction.

Bronchoalveolar lavage (BAL) was performed before and 10 minutes after inhalation challenge with plicatic acid in five patients with red cedar asthma. There was a significant release of histamine and leukotriene E4 into the BAL fluid in all the patients after challenge. Inhalation challenge with methacholine in six patients with nonoccupational asthma and inhalation challenge with plicatic acid in two subjects without asthma did not result in the release of mediators in the BAL fluid. These studies provide direct evidence that plicatic acid-induced bronchoconstriction was accompanied by increased levels of histamine and leukotriene E4 release, whereas a nonimmunologic induction of bronchoconstriction did not induce such local mediator release. BAL may provide a useful means of studying the pathogenesis of occupational asthma caused by exposure to low-molecular-weight compounds.

Adolescent↗

The rhesus rotavirus outer capsid protein VP4 functions as a hemagglutinin and is antigenically conserved when expressed by a baculovirus recombinant.

Rhesus rotavirus (RRV) gene 4 was cloned into lambda bacteriophage, inserted into a polyhedrin promoter shuttle plasmid, and expressed in Sf9 cells by a recombinant baculovirus. The baculovirus-expressed VP4 protein made up approximately 5% of the Spodoptera frugiperda-infected cell protein. Monoclonal antibodies that neutralize the virus bound to the expressed VP4 polypeptide, indicating that the expressed VP4 protein was antigenically indistinguishable from viral VP4. In addition, we have determined that the baculovirus-expressed VP4 protein bound to erythrocytes and functions as the RRV hemagglutinin. The endogenous hemagglutinating activity of the VP4 protein, like the virus, was inhibited by guinea pig antirotavirus hyperimmune serum and by VP4-specific neutralizing monoclonal antibodies. The human erythrocyte protein, glycophorin, also inhibited hemagglutination by RRV or the expressed VP4 protein and appears to be the rotavirus erythrocyte receptor. The baculovirus-expressed VP4 protein was conserved functionally and antigenically in the absence of other outer or inner capsid rotavirus components and represents a logical candidate for future immunological studies.

Animals↗

Oral lecithin improves ultrafiltration in patients on peritoneal dialysis.

Three patients on peritoneal dialysis (two on continuous ambulatory and one on intermittent) with severe ultrafiltration failure were treated with 2 capsules of Lecithin three times a day (containing of 1.08 g of phosphatidylcholine). Their ultrafiltration improved significantly to the point that their edema improved and were able to continue on peritoneal dialysis with fewer daily hypertonic exchange.

Administration, Oral↗

Release of leukotrienes in patients with bronchial asthma.

To investigate whether leukotrienes (LTs) are released into the bronchial fluid of patients with symptomatic asthma, bronchial lavage was carried out in 17 patients with mild to severe asthma and nine healthy subjects without asthma. LTE4 was detected in 15 of the 17 patients with asthma with reverse-phase high-performance liquid chromatography. The identify of LTE4 was confirmed by ultraviolet spectrometry and by positive ion fast atom-bombardment mass spectrometry. LTD4 was found in two patients and 20-OH-LTB4 in 12 patients. No LTs were detectable in the lavage fluid from any of the healthy subjects without asthma. The finding of LTs in bronchial lavage fluid from the patients with asthma despite bronchodilator and/or corticosteroid therapy suggests that these compounds may be important in asthma. However, the presence of significant quantities of LTE4 in patients with mild asthma requiring only intermittent bronchodilator therapy for control and the lack of correlation between LTE4 and pulmonary function also suggests that other factors may be important in determining the net end organ response. The present study points to the importance of studying the whole spectrum of mediators that are released. Analysis of bronchial lavage fluid may be useful in determining the relative role of these mediators and the effect of pharmacologic intervention.

Adult↗

Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA.

Transcription of the interleukin 1 beta (IL-1 beta) gene was studied by mRNA hybridization with a cDNA probe in the human promonocytic cell line U-937. Phorbol ester and lipopolysaccharide increased the steady-state level of IL-1 beta mRNA. Glucocorticoids markedly decreased IL-1 beta mRNA levels by two mechanisms. Transcription of the IL-1 gene was inhibited, as shown by in vitro transcription assays with nuclei isolated from glucocorticoid-treated cells. Moreover, kinetic analyses and pulse-labeling of mRNAs showed that glucocorticoids selectively decrease the stability of IL-1 beta mRNA, without affecting the stability of beta-actin and FOS mRNAs. Inhibition of the formation and effects IL-1 is a mechanism by which glucocorticoids can exert antiinflammatory and immunosuppressive effects.

Cycloheximide↗

Comparison of aqueous grain dusts, cotton dusts, and mold extracts by crossed immunoelectrophoretic techniques.

To evaluate the possibility that an immune response is involved in the pathogenesis of grain dust or cotton dust induced respiratory disease, 1 grain dust extract (A) was compared with 4 similar grain dust extracts, a cotton dust extract, and a mixture of fungal preparations, using crossed immunoelectrophoretic techniques and rabbit anti-A sera. All extracts demonstrated a significant number of shared antigenic determinants. These data suggest that grain and cotton dust may induce disease via a common pathogenic mechanism and putative agent(s).

Allergens↗

Pyruvate carboxylase, phosphate-dependent glutaminase and glutamate dehydrogenase in the developing rat small intestinal mucosa.

The activities of glutaminase and glutamate dehydrogenase in the small intestinal mucosa of infant rats were found to increase at the time of weaning. Pyruvate carboxylase activity, on the other hand, was very high during the suckling period and decreased to negligible values at weaning. It is suggested that gluconeogenesis in the infant mucosa occurs primarily via oxaloacetate and not via alpha-ketoglutarate.

Aging↗

A longitudinal study of the occurrence of bronchial hyperresponsiveness in western red cedar workers.

Two hundred twenty-seven workers in a western red cedar sawmill underwent methacholine bronchoprovocation testing at least 2 times during 3 surveys over a 2-yr period. At the first survey, workers completed a respiratory and occupational questionnaire, performed spirometry, gave serum for measurement of plicatic acid-specific IgE antibodies by radioallergosorbent testing, and had skin prick tests to detect atopy. Bronchial hyperresponsiveness was present initially in 18% of the workers. Approximately 15% of those with initially no hyperresponsiveness developed hyperresponsiveness during the follow-up period; 15% of those with initial hyperresponsiveness also lost it during follow-up. Development of hyperresponsiveness tended to coincide with a decrease in level of pulmonary function, whereas loss of hyperresponsiveness was associated with improvement in pulmonary function. Workers with either persistent bronchial hyperresponsiveness or with varying responsiveness had a higher prevalence of plicatic acid IgE antibodies and lower levels of initial pulmonary function than did workers with persistent nonresponsiveness. Workers with persistent hyperresponsiveness had higher initial estimated total airborne dust exposure than did other workers. Age, duration of sawmill employment, atopy, race, and cigarette smoking did not influence the occurrence of hyperresponsiveness. Levels of plicatic-acid-specific IgE antibodies did not change substantially over the 2 yr. These results indicate that immunologic sensitivity to plicatic acid and change in airway caliber are associated with the occurrence of bronchial hyperresponsiveness in cedar workers.

Allergens↗

Binding of peanut agglutinin to neuroblastomas and ganglioneuromas: a marker for differentiation of neuroblasts into ganglion cells.

Binding of peanut agglutinin (PNA), concanavalin A, Ricinus communis agglutinin, wheat germ agglutinin, soybean agglutinin, Ulex europaeus agglutinin 1, and Dolichos biflorus agglutinin was assessed in tissue sections of 4 cases of neuroblastoma (NB) to determine whether there were any differences in lectin binding among immature neuroblasts, maturing neuroblasts, and ganglion cells. Only PNA binding proved to be useful. This was assessed more fully in 17 cases of NB and 7 ganglioneuromas. PNA bound to immature neuroblasts in only 4 of 12 stroma-poor NB but to maturing neuroblasts and ganglion cells in 5 of 5 stroma-rich NB. PNA bound to ganglion cells in all 7 ganglioneuromas. The NB were categorized as favorable (7 cases) and unfavorable (10 cases), using the patients' ages and the histologic appearance and mitotic-karyorrhetic index of the resected tumor, and this was correlated with PNA binding. PNA bound to 6 of 7 NB with a favorable, and 3 of 10 with an unfavorable histologic type of NB (p less than 0.05). These studies suggest that neuroblasts acquire the capacity to bind to PNA as they differentiate into ganglion cells and that PNA binding is indicative of a favorable histologic type of NB.

Age Factors↗

Grain-dust extract induced direct release of mediators from human lung tissue.

To explore the mechanisms of grain dust-induced acute bronchoconstriction, extracts of grain dust were incubated with chopped human lung fragments. The supernatants of the incubation media were examined for the presence of leukotrienes and histamine with high-performance liquid chromatographic techniques. Human lung fragments responded to the extract of grain dust by releasing histamine in a dose-dependent manner. Moreover, leukotrienes (B4, D4, and E4 were also found to be released. The action of grain dust appeared to be independent of the complement pathway or cell cytotoxicity since the lung tissue released the chemical mediators in the absence of plasma and responded to further reaction with compound 48/80 after interaction with grain dust. These data demonstrate that grain-dust extract may induce the release of mediators of anaphylaxis by a nonimmunologic process. This may explain the occurrence of acute bronchoconstriction in some of the grain workers.

Allergens↗

A rabbit model of hypersensitivity to plicatic acid, the agent responsible for red cedar asthma.

We describe a rabbit model for the study of the immunogenicity and allergenicity of plicatic acid (PA), the small molecular weight compound in western red cedar responsible for occupational asthma in exposed workers. Specific anti-PA IgE as well as IgG antibodies could be raised, depending on the method of immunization. The sensitized rabbits reacted to antigenic challenge with PA-protein conjugates intravenously, with increases in respiratory frequency and pulmonary resistance. This animal model may be used for the further elucidation of the mechanism of occupational asthma induced by small molecular weight chemical compounds.

Animals↗

Plasma histamine after methacholine, allergen, and aspirin challenges.

Plasma histamine levels were measured by radio-enzymatic technique in seven patients following 10 challenges: five methacholine challenge tests, four antigen inhalation challenge tests, and one oral aspirin challenge test. Baseline plasma histamine was the same in all patients except in the aspirin-challenged patient, who had a higher baseline histamine level. There was no statistical change in the level of histamine throughout the test in either the methacholine-challenged or the antigen-challenged patients, whereas there was a marked increase in histamine levels in the aspirin challenged patient. A possible explanation is that methacholine and antigen are inhaled and therefore have primarily local effects on the lung, whereas oral aspirin has a systemic effect with consequently systemic changes in histamine which are detectable as changes in plasma level.

Adult↗

Acuity estimated by visually evoked potentials is affected by scaling.

Seven subjects whose corrected Snellen acuities were normal had their monocular acuities (14 eyes) tested by visually evoked potentials (VEPs) elicited by eight checkerboard patterns which reversed 15 times per second. Check size ranged from 20 to 3.4 min. arc. Monocular VEP acuities were determined by least squares regression with linear or logarithmic scales of amplitude and pattern size. Pattern size was measured as arc minutes (horizontal size) or fundamental spatial frequency of the checkerboard. The extrapolated VEP acuities were obtained by analyses of variance and post hoc tests. The presence of statistically significant differences in VEP acuity which result from varying combinations of stimulus and response scales indicates a need for caution in selecting scales for VEP estimates of visual acuity.

Analysis of Variance↗