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Biomedical subjects

D Wu

Publications and source records attributed to D Wu.

At least 487 records · Page 27Linked to original sources
PubMed1993

Determination of airborne cadmium in environmental tobacco smoke by instrumental neutron activation analysis with a compton suppression system.

Concentrations of cadmium, a toxic trace element, were measured in the indoor air of several public places where environmental tobacco smoke was present. Particulate-phase cadmium concentrations were determined by analyzing air filter samples using epithermal instrumental neutron activation analysis in conjunction with a Compton suppression gamma-ray detection system, in which the detection limit for cadmium was reduced to a few nanograms per filter. A cascade impactor and a personal filter sampler were used to collect the indoor suspended particulate matter for size-fractionated mass as well as total mass, respectively. Results show that where environmental tobacco smoke is present, cadmium concentrations are significantly higher than background and that about 80% of the cadmium found in indoor airborne particulate matter is associated with particles with aerodynamic diameters less than 1.8 microns. In one instance, airborne cadmium concentrations in a music club were found to be 38 ng/m, which is at least 30 times higher than background.

Air Pollutants↗
PubMed1993

Activation of phospholipase C beta 2 by the alpha and beta gamma subunits of trimeric GTP-binding protein.

Cotransfection assays were used to show that the members of the GTP-binding protein Gq class of alpha subunits could activate phospholipase C (PLC) beta 2. Similar experiments also demonstrated that G beta 1 gamma 1, G beta 1 gamma 5, and G beta 2 gamma 5 could activate the beta 2 isoform of PLC but not the beta 1 isoform, while G beta 2 gamma 1 did not activate PLC beta 2. To determine which portions of PLC beta 2 are required for activation by G beta gamma or G alpha, a number of PLC beta 2 deletion mutants and chimeras composed of various portions of PLC beta 1 and PLC beta 2 were prepared. We identified the N-terminal segment of PLC beta 2 with amino acid sequence extending to the end of the Y box as the region required for activation by G beta gamma and the C-terminal region as the segment containing amino acid sequences required for activation by G alpha. Furthermore, we found that coexpression of G alpha 16 and G beta 1 gamma 1 but not G beta 1 gamma 5 in COS-7 cells was able to synergistically activate recombinant PLC beta 2. We suggest that G alpha 16 may act together with free G beta 1 gamma 1 to activate PLC beta 2, while G alpha 16 may form heterotrimeric complexes with G beta 1 gamma 5 and be stabilized in an inactive form. We conclude that the regions of PLC beta 2 required for activation by G beta gamma and G alpha are physically separate and that the nature of the G beta subunit may play a role in determining the relative specificity of the G beta gamma complex for effector activation while the nature of the G gamma subunit isoform may be important for determining the affinity of the G beta gamma complex for specific G alpha proteins.

Amino Acid Sequence↗
PubMed1993

Radiofrequency ablation in multiple accessory pathways and the physiologic implications.

The presence of multiple accessory pathways was noted in 24 of 210 consecutive patients (12 males and 12 females aged 15 to 77 years [mean +/- SD 43 +/- 16]) with the Wolff-Parkinson-White syndrome who underwent electrophysiologic study and radiofrequency ablation. Six had 3 and 18 had 2 accessory pathways. There were 25 manifest and 29 concealed accessory pathways. The location of the accessory pathways was in the left free wall in 22, the right free wall in 17, the left posterior portion of the ventricular septum in 8, the right posterior portion of the ventricular septum in 6, and the midseptum in 1. The success rate of accessory pathway ablation and the fluoroscopic time in these 24 patients with multiple accessory pathways were 89% and 78 +/- 66 minutes, respectively, whereas they were 98% (p < 0.01) and 36 +/- 37 minutes (p = 0.01) in the 186 patients with a single accessory pathway. The mean applications, the power level of the radiofrequency current and the application duration in these 24 patients were 21 +/- 22, 30 +/- 3 W, and 27 +/- 10 seconds, respectively. In the 186 patients with a single accessory pathway, they were 9 +/- 12 applications (p = 0.02), 30 +/- 4 W (p = NS) and 26 +/- 9 seconds (p = NS), respectively. Seventeen of the 24 patients had a follow-up electrophysiologic study 89 +/- 40 days after ablation, and 2 (12%) had resumption of a right and left accessory pathway conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Manipulation of electroosmotic flow in capillary electrophoresis.

This paper reports the use of surfactant and polymer-C18 coated capillaries that allow manipulation of electroosmotic flow (EOF). Although this approach to the control of EOF involves the preparation and use of multiple capillaries, all the coatings were prepared by a single procedure. It is shown that the ability to control EOF allows optimization of both separation time and resolution. In the case of proteins, low EOF maximizes resolution whereas high flow gives the shortest analysis time. It should be noted that proteins are a special case and this conclusion may not be true with other molecular species. Through selection of a specific coating, it is possible to complete a separation in the shortest time while maintaining sufficient resolution to give baseline resolution of proteins. The various coated capillaries were examined in capillary zone electrophoresis (CZE) and capillary isoelectric focusing (cIEF) separations of native protein standards and hemoglobin variants. Separation of glycosylated hemoglobin A1 variants was achieved by cIEF within 10 min, including the focusing time. Good run-to-run reproducibility was obtained by flushing the capillary with the coating solution between analyses.

Electrophoresis↗
PubMed1993

Identification of critical regions on phospholipase C-beta 1 required for activation by G-proteins.

In order to determine which portion of phosphoinositide-specific phospholipase C (PLC)-beta 1 is required for activation by G alpha q, a series of specific deletions and truncations of PLC-beta 1 cDNA were prepared. After transfection of COS-7 cells with these cDNA clones, the activity and localization of the expressed proteins were determined. Specific deletions in the C-terminal end of the protein did not lead to loss of intrinsic enzymatic activity but did result in loss of the ability to be activated by G alpha q. The region required for activation was localized to the amino acid sequence corresponding to residues 903-1142 of PLC-beta 1. This region was further subdivided into two sequences; one extending from residues Thr-903 to Gln-1030 that was required for particulate fraction association as well as for activation by G alpha q and the other extending from residues Gln-1030 to Leu-1142 that was required for interaction with G alpha subunits. These results were confirmed by the observation that the C-terminal portion of PLC-beta 1, when co-expressed with the muscarinic acetylcholine receptor type 1 or the alpha 1C-adrenergic receptor in COS-7 cells, markedly inhibited ligand-induced release of inositol phosphates. In an in vitro system, two peptides derived from the G-protein interaction region at the C terminus were found to inhibit the guanosine 5'-3-O-(thio)triphosphate-dependent activation of PLC-beta 1 by G alpha q. This further localized the sites on PLC-beta 1 which are involved in interaction with G-protein alpha subunits.

Amino Acid Sequence↗
PubMed1993

Opioid-induced stimulation of fetal respiratory activity by [D-Ala2]deltorphin I.

[D-Ala2]deltorphin I effects on fetal respiratory activity was characterized to determine the role delta-opioid receptors play in modulating fetal respiratory activity. [D-Ala2]deltorphin I, infused at 0.3 or 100 micrograms/h, intracerebroventricularly (i.c.v.), stimulated fetal respiratory activity without changing blood pH, PCO2 or PO2. Stimulation by 0.3 micrograms/h, but not 100 micrograms/h, was blocked by i.c.v. infusion of the delta-opioid receptor antagonist, naltrindole. Stimulation by 100 micrograms/h was blocked by the mu 1-opioid receptor antagonist naloxonazine. These data suggest stimulation of fetal respiratory activity by 0.3 micrograms/h [D-Ala2]deltorphin I are mediated specifically through delta-opioid receptors; while [D-Ala2]deltorphin I at 100 micrograms/h is no longer selective for the delta-opioid receptor, and the stimulation may be mediated through the mu 1-opioid receptor.

Animals↗
PubMed1993

Combined effects of streptozotocin-induced diabetes plus 4-methylpyrazole treatment on rat liver cytochrome P4502E1.

The content and activity of cytochrome P4502E1 is increased in the diabetic state, primarily due to stabilization of the P4502E1 mRNA. Chemical inducers such as 4-methylpyrazole (4MP) increase P4502E1 content by stabilization of the protein. Experiments were carried out to evaluate the combined effects of 4MP and streptozotocin-induced diabetes on P4502E1 protein, catalytic activity and mRNA levels. Immunoblots showed an elevated content of P4502E1 after treatment with 4MP or streptozotocin, which was further increased when the two treatments were combined. Similarly, catalytic activity with effective substrates for P4502E1 was increased by the two separate treatments, and further increased by combined treatment. In all treatment groups, catalytic activity was strongly inhibited by antibody against P4502E1. The content of P4502E1 and catalytic activity in the 4MP plus streptozotocin group appeared to be additive of the values for the separate treatments. P4502E1 mRNA levels were elevated by the streptozotocin treatment but not by 4MP treatment; combined treatment with both inducers did not elevate P4502E1 mRNA levels beyond the increase produced in the diabetic state. CCl4 decreased cellular viability in hepatocytes from streptozotocin- or 4MP-treated rats, and increased toxicity was found after treatment with both inducers. These results contrast the mechanisms of induction of P4502E1 by streptozotocin and 4MP, and suggest that each individual mechanism is maintained when the two inducers are administered such that effects on P4502E1 protein and catalytic activity, but not mRNA, are additive of values found for each inducer alone. The diabetic state may be associated with increased sensitivity to toxins which are activated by P4502E1, especially if chemical inducers similar to 4MP, e.g., ethanol, isoniazid are also present.

Animals↗
PubMed1993

Effect of potassium deficiency and gossypol on urinary N-acetyl-beta-glucosaminidase excretion in the rat.

Some men receiving gossypol in China developed elevated urinary N-acetyl-beta-glucosaminidase (NAG) levels and hypokalemia. Since idiopathic hypokalemia occurs in China, hypokalemic nephropathy may have caused the elevated NAG levels. To learn if gossypol is directly nephrotoxic, we treated rats with a normal or low potassium diet with or without gossypol. The low potassium diet produced high NAG levels rather than the gossypol. This indicates the importance of differentiating hypokalemic nephropathy from drug nephrotoxicity in regions where idiopathic hypokalemia occurs.

Acetylglucosaminidase↗
PubMed1993

Eicosanoids derived from arachidonic and eicosapentaenoic acids inhibit T cell proliferative response.

Eicosanoids derived from arachidonic acid (PGE2 and LTB4) have been shown to be involved in the control of mitogen-induced proliferation of lymphocytes but the effects of (n-3) polyunsaturated fatty acids (PUFA)-derived eicosanoids (PGE3 and LTB5) on mitogenic response have not been well described. Supplementation with (n-3) PUFA decreases lymphocyte proliferation in human and animal models. The present study was designed to compare the effect of (n-3)- and (n-6)-derived eicosanoids on mitogenic response. Mouse splenocytes and human peripheral blood mononuclear cells (PBMC) were cultured in the presence or absence of the T cell mitogen Concanavalin A (CON A) with and without the addition of PGE2, LTB4, PGE3 and LTB5 at several concentrations. Lymphocyte proliferation was determined by measuring incorporation of [3H]thymidine into newly synthesized DNA. Both (n-3) and (n-6)-derived eicosanoids inhibited T cell mitogen-induced lymphocyte proliferation in human PBMC and murine splenocytes. The addition of PGE3 and LTB5 decreased Con A-induced mitogenic response in human PBMC more than the same concentration of PGE2 and LTB4 (e.g. -28.7 +/- 4.2% with 10(-9) M PGE3 vs -9.4 +/- 6.3% with 10(-9) M PGE2, P = 0.05 and -95.5 +/- 1.6% with 10(-11) M LTB5 vs -49.2 +/- 3.8% with 10(-11) M LTB4, p < 0.001). A similar trend was observed in murine splenocytes. It is concluded that PGE3 and LTB5 are as potent and at some doses more potent than PGE2 and LTB4 in inhibiting lymphocyte proliferation when added in vitro. These data suggest that eicosanoids derived from (n-3) PUFA may contribute to the (n-3) PUFA-induced suppression of lymphocyte proliferation.

Alprostadil↗
PubMed1993

Prognosis after a first Q-wave myocardial infarction in ethnic Chinese people: a prospective study.

The prognosis after a first Q-wave myocardial infarction was investigated in 206 Chinese patients of 65 years or younger who had a predischarge cardiac catheterization and coronary angiography. Three patients studied were lost to follow-up. In the remaining 203 patients with ages of between 28 and 65 years, 101 (49.8%) had 0- or 1-vessel disease, 56 (27.6%) had 2-, and 38 (18.7%) had 3-vessel disease. Significant left main coronary artery stenosis was noted in 8 (3.9%). During a mean follow-up of 33 months, 33 (16.3%) patients had 36 episodes of cardiac events, and 16 (7.9%) died of cardiac causes. Stepwise logistic regression analysis revealed that the left ventricular ejection fraction and left main coronary artery disease were predictors of cardiac mortality, while age and the extent of coronary artery disease were predictors of total cardiac events. There was no variable that could predict recurrence of myocardial infarction.

Aged↗
PubMed1993

A simple technique for selective radiofrequency ablation of the slow pathway in atrioventricular node reentrant tachycardia.

OBJECTIVES: A simple technique was designed for radiofrequency ablation therapy of atrioventricular (AV) node reentrant tachycardia. BACKGROUND: This technique was based on the hypothesis that slow pathway conduction reflects conduction through the compact node and its posterior atrial input. METHODS: A total of 100 consecutive patients were studied; there were 37 men and 63 women, with a mean age of 48 +/- 15 years. All 100 patients had induction of sustained tachycardia with (51 patients) or without (49 patients) administration of isoproterenol or atropine, or both. The ablation catheter was initially manipulated to record the largest His bundle deflection from the apex of Koch's triangle. It was then curved downward and clockwise to the area of the compact node when His deflection was no longer visible and the ratio of atrial to ventricular electrogram was < 1. The radiofrequency current was delivered from the 4-mm tip electrode a mean of 5 +/- 7 times at a power of 25 +/- 4 W for a duration of 21 +/- 4 s. The total fluoroscopic time was 19 +/- 11 min. RESULTS: Selective ablation (56 patients) or modification (26 patients) of the slow pathway without affecting anterograde and retrograde fast pathway conduction was achieved in 82 patients. Ablation or modification of both the retrograde fast pathway and the slow pathway but with preservation of anterograde fast pathway conduction was noted in 12 patients. Ablation or modification of the retrograde fast pathway alone or both anterograde and retrograde fast pathway conduction was noted in three patients. Complete AV node block occurred in three patients. Seventy-three patients had no induction of echo beats or tachycardia and 24 patients had induction of a single echo beat after ablation. Follow-up study was performed in 62 patients 76 +/- 18 days after ablation. Thirty-nine patients had no induction of echo beats or tachycardia, 22 had induction of echo beats alone and 1 patient had induction of sustained tachycardia. CONCLUSION: Selective ablation of the slow AV node pathway can be achieved by a simple procedure with a high success rate and few complications.

Adolescent↗
PubMed1993

Inhibition by fluoxetine of cytochrome P450 2D6 activity.

Potent inhibition of cytochrome P450 2D6 (CYP2D6) in human liver microsomes by fluoxetine and its major metabolite norfluoxetine was confirmed (apparent inhibition constant values, 0.2 mumol/L). Several other serotonergic agents were also found to be competitive inhibitors of this genetically polymorphic enzyme. The O-demethylation ratio of dextromethorphan that expressed CYP2D6 activity in 19 patients receiving fluoxetine fell in the region of the antimode separating the O-demethylation ratio values observed in 208 extensive metabolizers from 15 poor metabolizers of a control group of healthy subjects. Inhibition of CYP2D6 activity in patients undergoing treatment with fluoxetine or other serotonin uptake inhibitors could contribute to toxicity or attenuated response from concurrent medications that are substrates of this enzyme. Other in vitro studies indicated that CYP2D6 catalyzes the O-demethylation of oxycodone to form oxymorphone. This reaction was inhibited by fluoxetine and its normetabolite in liver microsomes from both extensive and poor metabolizer individuals, indicating that these compounds are not selective inhibitors of CYP2D6 activity.

Adult↗
PubMed1993

Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone.

1. In microsomes prepared from three human livers, methadone competitively inhibited the O-demethylation of dextromethorphan, a marker substrate for CYP2D6. The apparent Ki value of methadone ranged from 2.5 to 5 microM. 2. Two hundred and fifty-two (252) white Caucasians, including 210 unrelated healthy volunteers and 42 opiate abusers undergoing treatment with methadone were phenotyped using dextromethorphan as the marker drug. Although the frequency of poor metabolizers was similar in both groups, the extensive metabolizers among the opiate abusers tended to have higher O-demethylation metabolic ratios and to excrete less of the dose as dextromethorphan metabolites than control extensive metabolizer subjects. These data suggest inhibition of CYP2D6 by methadone in vivo as well. 3. Because methadone is widely used in the treatment of opiate abuse, inhibition of CYP2D6 activity in these patients might contribute to exaggerated response or unexpected toxicity from drugs that are substrates of this enzyme.

Adolescent↗
PubMed1993

Expression, purification, and characterization of recombinant Drosophila choline acetyltransferase.

A cDNA for Drosophila choline acetyltransferase (EC 2.3.1.6; ChAT) was fused with a polyhistidine sequence and expressed in Escherichia coli. The recombinant enzyme was purified to a specific activity of 500 mumol/min/mg of protein using metal affinity chromatography and ion exchange chromatography. Kinetic properties of the recombinant enzyme did not differ significantly from those previously determined. Circular dichroism (CD) spectra revealed that the secondary structure of the enzyme is largely alpha-helical. Intrinsic fluorescence spectra of the enzyme indicate that its tryptophan residues are buried. Neither CD nor fluorescence spectra changed significantly in the presence of substrates. The cysteine content of the recombinant Drosophila ChAT was determined to be 16 in the absence and 22 in the presence of 6 M guanidine hydrochloride. Finally, crystallization of recombinant Drosophila ChAT was achieved.

Animals↗
PubMed1993

Radiofrequency ablation therapy in three patients with paroxysmal atrial tachycardia.

Radiofrequency ablation therapy was performed in three patients with paroxysmal atrial tachycardia. There were two females and one male, aged 80, 63, and 75 years, respectively. All three patients had induction of sustained atrial tachycardia. The tachycardia could be terminated by overdrive atrial pacing or atrial premature stimulation; it could also be terminated by intravenous bolus of adenosine triphosphate. In all three patients, there was no fragmented atrial electrograms recorded within the right atrium, and there was no ventriculo-atrial conduction during ventricular pacing. The earliest atrial activation during tachycardia in these three patients was registered, respectively, at a site slightly posterior and inferior to the His-bundle recording site, at the anterior-superior border of Koch's triangle slightly posterior to the His-bundle recording site, and at the mid-lateral aspect of the right atrium over the crista terminalis at the junction of right atrial appendage and sinus venarum. Radiofrequency current was delivered to the site of the earliest atrial activation during tachycardia through a 4-mm tip electrode catheter. It resulted in termination of tachycardia and ablation of the tachycardia focus. Follow-up observation over a period of 16, 15, and 4 months, respectively, in these three patients showed no recurrence of tachycardia. A repeat electrophysiological study was performed 52 and 63 days after ablation in two patients and revealed no induction of atrial tachycardia.

Aged↗
PubMed1993

A 20-kilodalton protein preserves cell viability and promotes CytA crystal formation during sporulation in Bacillus thuringiensis.

The effect of a 20-kDa protein on cell viability and CytA crystal production in its natural host, Bacillus thuringiensis, was studied by expressing the cytA gene in the absence or presence of this protein. In the absence of the 20-kDa protein, B. thuringiensis cells either were killed during sporulation (strain cryB) or produced very small CytA crystals (strain 4Q7). Expression of cytA in the presence of the 20-kDa protein, however, preserved cell viability, especially in strain cryB, and in both strains yielded bipyramidal crystals of the CytA protein that were larger than those of wild-type B. thuringiensis. These results suggest that the 20-kDa protein promotes crystal formation, perhaps by chaperoning CytA molecules during synthesis and crystallization, concomitantly preventing the CytA protein from interacting lethally with the bacterial host cell.

Bacillus thuringiensis↗
PubMed1993

Pharmacological characterization of muscarinic receptors in neonatal rat cardiomyocytes.

[N-methyl-3H]scopolamine methylchloride ([3H]NMS) was used to characterize the muscarinic receptors (mAChRs) in the intact cardiomyocytes. The specific binding of [3H]NMS was proportional to cell concentration, saturable with respect to [3H]NMS concentration, and time dependent. Scatchard analysis of binding isotherms showed that [3H]NMS bound to the freshly isolated and cultured cardiomyocytes with dissociation constants of 275 +/- 64 and 207 +/- 20 pM as well as maximum receptor densities of 0.13 +/- 0.09 and 5.36 +/- 0.20 fmol/10(5) cells, respectively. Heterogeneity of mAChRs was demonstrated by competitive binding experiments against [3H]NMS with M2 and M3 antagonists. These receptors (80%) exhibited high affinities for 11-([2-[(diethylamino)methyl]-1-piperidinyl]-acetyl)-5,11-dihydro- 6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX-116) and methoctramine similar to those of M2 subtype. The low-affinity M2 antagonist binding constants were close to those reported for M3 receptors and possessed high affinity for 4-diphenylacetoxyl-N-methylpiperidine (4-DAMP) and hexahydrosiladifenidol. On the basis of biochemical studies, AF-DX-116 blocked adenosine 3',5'-cyclic monophosphate (cAMP) inhibition with high affinity (pKB 7.4), while it antagonized inositol phosphate formation with low affinity (pKB 6.5). 4-DAMP possessed high affinity in blocking inositol phosphate formation (pKB 9.0) and low affinity for antagonism of cAMP inhibition (pKB 7.7). Although no other muscarinic receptor mRNA has been detected in these cells, these data suggest the presence of a second population of mAChRs, which may not be identical to the classical cardiac "M2" receptors.

Animals↗