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D Ng

Publications and source records attributed to D Ng.

53 records · Page 3Linked to original sources
PubMed1991

Differential effect of diltiazem and TA-3090 on calcium homeostasis of neutrophils.

The effects of diltiazem and TA-3090, an 8-chloro analog of diltiazem, on cellular responses and calcium homeostasis of human neutrophils were investigated. TA-3090, at 10 to 20 microM, enhanced lysozyme release and superoxide generation induced in neutrophils by n-formyl-methionyl-leucyl-phenylalanine (FMLP). Higher concentrations of TA-3090 inhibited responses at IC50s between 70 and 85 microM. Diltiazem by comparison inhibited responses at an IC50 of about 200 microM. The two drugs had little or no effect on early signaling events: inositol 1,4,5-trisphosphate formation triggered by FMLP was not affected. Moreover, 500 microM TA-3090 or diltiazem did not significantly affect FMLP-triggered Ca2+ transients. (Cytoplasmic free Ca2+ levels ([Ca2+]i) were monitored in fura-2-loaded neutrophils.) Diltiazem alone caused a limited influx of extracellular Ca2+ which increased basal [Ca2+]i by twofold. Internal Ca2+ stores were not released. TA-3090, in contrast, induced a biphasic rise in [Ca2+]i--an initial mobilization of intracellular Ca2+ stores was followed after 10-15 min by a persistent influx of extracellular Ca2+ which increased [Ca2+]i to 1.3 +/- 0.7 (SD) microM. Complementary studies with semipermeabilized neutrophils showed that TA-3090 but not diltiazem directly released Ca2+ from intracellular stores. In TA-3090-treated cells, lactate dehydrogenase release was correlated with delayed influx of extracellular Ca2+. The chelation of extracellular Ca2+ by EGTA prevented LDH release. Present results show that TA-3090 and diltiazem initially blocked cell signaling at steps subsequent to phospholipase C activity. With TA-3090-treated cells, elevated [Ca2+]i ensuing from prolonged incubations likely activated inappropriate reactions leading to cell lysis and death.

Calcium↗
PubMed1991

Analysis of an Escherichia coli dnaB temperature-sensitive insertion mutation and its cold-sensitive extragenic suppressor.

An Escherichia coli mutant, ts121, was isolated following random insertional mutagenesis using phage lambda Mu transposition. The mutant phenotype includes inability to form colonies at temperatures above 38 degrees C and inability to propagate phage lambda at all temperatures. A lambda i434 cI- (ts121)+ transducing phage was isolated on the basis of its ability to form plaques on ts121 mutant bacteria. Using this transducing phage, it was shown through complementation and protein analyses, that the ts121 mutation is located in the dnaB gene. The exact insertion event was identified by polymerase chain reaction amplification of the DNA sequences containing the insertion junction. The mutational insertion event in ts121 was mapped precisely between base pairs 1514 and 1515 of the dnaB gene. This result predicts that the mutant dnaB protein has lost its six terminal amino acids. The reading frame shifts into Mu-specific DNA sequences resulting in an additional 20 amino acid residues. The E. coli wild type dnaB protein participates in host replication and interacts with lambda P protein to initiate phage lambda DNA replication. Our results demonstrate that the extreme carboxyl end of the dnaB protein is required for productive interaction with the lambda P replication protein at all temperatures, and is important for dnaB function at temperatures above 38 degrees C. Cold-sensitive extragenic suppressors of the ts121 mutation were isolated on the basis of their ability to restore colony formation at 42 degrees C. One of these extragenic suppressors was mapped at 54 min on the E. coli genetic map and localized to the suhB gene, whose product may affect the expression of a number of genes at the translational level.

Bacterial Proteins↗
PubMed1991

Work-related burns: a 6-year retrospective study.

During the 6 years from July 1984 to May 1990, 193 patients (30.2 per cent of all patients) were admitted to our regional adult burn centre, for treatment of work-related burn injuries. The median age of patients was 32.5 years (range 18-64 per cent), and 94 per cent were males. Fifty-nine per cent of the patients came from metropolitan Toronto, and 40 per cent from rural Ontario. Most of the patients (97.3 per cent) were referred to the burn centre within 24 h of their injury. The most common aetiology was electrical injury (29.5 per cent), followed by flame (24.4 per cent), contact (10.4 per cent), flash (9.8 per cent), tar and asphalt (9.3 per cent), scald (7.8 per cent), chemical (5.1 per cent), steam (4.7 per cent) and grease (1 per cent). Within the electrical burn group, about one-half were flash burns, one-quarter were clothing fire injuries, and one-quarter were contact injuries. These occupational burns tended to be extensive injuries. The median body surface area (BSA) was 16.5 per cent, with a median full thickness (FT) component of 5.0 per cent. The average length of stay was 20.0 days. Inhalation injury requiring intubation occurred in 14.8 per cent of patients. Sepsis--confirmed by positive blood cultures--developed in 14 per cent of the patients, at an average time of 8.8 days postburn. Staphylococcus aureus was the commonest organism isolated from blood cultures. Pneumonia occurred in 6.3 per cent of patients. A total of 207 surgical procedures was performed on 113 of the 193 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational↗
PubMed1990

Auranofin modulated cytoplasmic free calcium in neutrophils by mobilizing intracellular calcium and inhibiting protein kinase.

The effect of the lipophilic gold compound, auranofin (AUR) on the calcium homeostasis of human neutrophils treated with or without n-formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated. In agreement with previous reports, FMLP induced a rapid release of intracellular Ca2+ stores followed by a smaller influx of extracellular Ca2+. AUR and staurosporine enhanced while phorbol 12-myristate 13-acetate suppressed the secondary influx of Ca2+. Mn2(+)-quenching-of-fluorescence studies indicate that phorbol 12-myristate 13-acetate incubation blocked cation entry. AUR or staurosporine potentiation of FMLP effects on cytoplasmic free Ca2+ [( Ca2+]i) was attributed to suppression of negative feedback effects of protein kinase C. AUR (5-45 microM) per se induced a slow release of internal Ca2+ stores followed by a delayed influx of extracellular Ca2+. Control studies showed that AUR did not induce the formation of inositol 1,4,5-trisphosphate, lyse cells, or promote dye leakage. Dithiothreitol suppressed the AUR effect. AUR triggered biphasic but smaller increases in [Ca2+]i of neutrophil cytoplasts. Studies with permeabilized neutrophils showed that AUR directly released Ca2+ from internal stores. By comparison, gold sodium thiomalate, which had no effect on intact cells, also released Ca2+ from permeabilized cells. Present results indicate that AUR modulated [Ca2+]i directly by mobilized Ca2+ from multiple storage sites and indirectly by inhibiting protein kinase C.

Auranofin↗
PubMed1990

Cobalt as a gastric juice volume marker: comparison of two methods of estimation.

We investigated the use of cobalt-EDTA, a novel, nonabsorbable liquid phase marker, in the estimation of secretory volumes during topical misoprostol (synthetic PGE, analog) administration in the canine chambered gastric segment. We compared atomic absorption spectrophotometry (AAS) and instrumental neutron activation analysis (INAA) in the estimation of [Co]. Mucosal bathing solutions containing cobalt-EDTA were instilled into and recovered from the chamber by gravity every 15-min period as follows: (i) basal--60 min; (ii) misoprostol periods--150 min (plus 0.1-, 1-, 10-, 100-, and 1000-micrograms doses of misoprostol for two periods per dose). The recovered solutions were analyzed for [Co] by AAS and INAA. Total cobalt recovery by AAS after chamber washout was 102.97 +/- 0.98%. Mean +/- SE volumes (12.14 +/- 0.33 and 13.24 +/- 0.60 ml/15 min) obtained respectively from AAS and INAA were significantly higher (P less than 0.001) than the recovered mean volumes (10.51 +/- 0.17 ml/15 min). The percentage error in volume collection increased (range: 9.3-52.7%) with the volume of secretion. Values of [Co] obtained by the two techniques were comparable and not significantly different from each other (P greater than 0.05). INAA-estimated mean +/- SE [Co] showed consistently higher coefficients of variation. Spectra obtained for all samples during INAA measurements showed significant Compton background activity from 24Na and 38Cl. Cobalt-EDTA did not grossly or histologically damage the gastric mucosa. We conclude that cobalt is not adsorbed, absorbed, or metabolized, and is a suitable and reliable volume marker in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation Analysis↗
PubMed1989

Serum vitamins A and E, beta-carotene, and selenium in patients with breast cancer.

A total of 89 subjects including 30 breast cancer patients with distal metastases, 29 patients with benign breast disease, and 30 healthy subjects were studied. Serum samples from these subjects were obtained from the National Cancer Institute (NCI) Breast Cancer Serum Bank, Bethesda. Serum concentrations of vitamin A and its transport proteins (prealbumin and retinol-binding protein [RBP]), beta-carotene, vitamin E, and selenium were determined. For each of these parameters the mean for the breast cancer patients was lower than that of the healthy subjects. The differences between healthy subjects and patients with either breast cancer or benign breast disease were, however, statistically significant only in the case of RBP (p less than 0.05). In the case of vitamin A and its transport proteins these differences were reduced by comparing the cancer patients with the benign breast disease patients rather than with the healthy controls. This indicates that the low serum levels for those three parameters may be merely a consequence of disease in general rather than a feature of cancer per se.

Breast Diseases↗
PubMed1989

Ionic fluxes induced by topical misoprostol in canine gastric mucosa.

We studied the dose response of ionic fluxes in canine chambered gastric segment mucosa to increasing doses of topical misoprostol (0.1, 1, 10, 100, and 1000 micrograms). The fluxes were also correlated with the simultaneous changes in focal gastric mucosal blood flow measured by laser-Doppler flowmetry. After misoprostol administration, there was a dose-dependent increase in focal gastric mucosal blood flow (Emax = 8.23 +/- 3.25 V at 10 micrograms; ED50 = 1.05 micrograms), pH, and the outputs of ions (Na+, K+, Cl-, and HCO3-) and fluid (Emax for pH and fluxes greater than or equal to 1000 micrograms). ED50 values for these outputs ranged from 215.40 to 340 micrograms (mean +/- SE = 279.08 +/- 24.27 micrograms). H+ output showed a dose-dependent decrease to zero at the 10-micrograms dose, the dose at and after which net HCO3- secretion became obvious. The slopes of the dose-response curves for the fluxes of fluid, Na+, K+, Cl-, and HCO3- were significantly different (p less than 0.01) from the slope of the curve for mucosal blood flow changes. There were no correlations between the changes in these fluxes and blood flow changes. Na+ and Cl- were the predominant cation (98.84%) and anion (98.19%), respectively, in the misoprostol-induced secretion. Misoprostol stimulates a composite alkaline gastric nonparietal secretion, predominantly Na+ and Cl-, but also containing K+ and HCO3-. Our results suggest different mechanisms for the effects on nonparietal secretion and focal gastric mucosal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1982

Novel calcium channels used for lanthanide ion-induced adrenal catecholamine release.

Catecholamine release by La3+, Ce3+, Pr3+, or Nd3+ from isolated bovine adrenals requires the presence of calcium in the perfusing medium. Calcium dependent, La3+-induced adrenal catecholamine release is enhanced at low pH and only slightly inhibited by pretreatment with the calcium channel blocker, verapamil. Since calcium channels in adrenal medulla used by lanthanides are not effectively blocked by hydrogen ions or by verapamil, they must be different from the calcium channels normally opened by the physiological neuromediator, acetylcholine.

Adrenal Glands↗
PubMedDate not supplied

Is there a link between breast cancer and abortion: a review of the literature.

The hormonal changes that take place in pregnancy cause breast tissue to proliferate and differentiate. Abortion interrupts this process and may leave the proliferated, undifferentiated breast tissue at higher risk of carcinogenesis. This review explains the supposed difference in effects of induced and spontaneous abortion upon the breast tissue and examines the literature for a link with breast cancer. Additional subcategories examined include parity, number of abortions, gestation, and maternal age at abortion. A comparison of retrospective and prospective studies is made and possible sources of bias are identified. There is no evidence to support a link between spontaneous abortion and breast cancer. Absence of a link with induced abortion is less clear, and further research should concentrate on investigating any relationship. We suggest that prospective research is used, with point of entry at first termination.

Abortion, Induced↗
PubMedDate not supplied

Coupling efficiencies of amino acids in the solid phase synthesis of peptides.

The "classical" Merrifield method was used to synthesize over 500 peptides using Boc-benzyl strategy. The peptides were prepared either manually or on a Beckman 990B synthesizer or an Applied Biosystems 430A synthesizer. Each coupling of Boc amino acid to the growing peptide on the resin was monitored with the ninhydrin reaction. Couplings were considered "incomplete" if there was 99% or less coupling and "high incomplete" if there was 98% or less coupling. The efficiency of coupling was evaluated in regard to the specific amino acids involved in the coupling reaction and to the length of the peptide at the time of the coupling. The most difficult carboxyl-reacting amino acids were histidine, threonine, arginine, valine, isoleucine and glutamine; the most difficult amine reacting residues were glutamine, leucine, alanine, arginine and isoleucine. The number of "incomplete" and "high incomplete" couplings and the total number of monitored couplings of each of the 20 carboxyl-reacting amino acids when reacting with each of the 20 amine-reacting residues were tabulated. Coupling efficiencies decreased with the length of the peptide. The conclusion of this study is that, with the chemistries and methods used in this group of peptides, no amino acid coupling can be predicted to be complete with a single coupling reaction. The study points to the need for on-line determination of coupling efficiency during the synthesis in which a recoupling step is initiated when the first coupling is incomplete.

Amino Acids↗