Rapid plasma clearance and metabolism in vivo of a phosphorothioate oligodeoxynucleotide with a single, internal phosphodiester bond.
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Animals↗
Biomedical subjects
D Wu
Publications and source records attributed to D Wu.
Fine matrix mapping of the macular region in normal subjects.
Using a Humphrey field analyzer and fine matrix mapping, we measured photopic and scotopic thresholds for a blue light stimulus at 100 locations on a 9 degrees by 9 degrees matrix of 1 degree spacing centered at the fovea in 14 normal subjects. Additionally, trial lenses were used to investigate the effect of refractive error. Under photopic conditions the mean sensitivity varied by less than 1 dB over this region. Under scotopic conditions the central values were reduced in sensitivity by 15 dB compared with those at 4 degrees eccentricity. Defocus showed less than 1.2 dB loss with 1.00D of refractive error under photopic condition. The results reflect the properties of rod and cone photoreceptors and the effects of the rod mosaic near the fovea. This technique is a sensitive test of macular visual function.
Adult↗
Ethanol increases content and activity of human cytochrome P4502E1 in a transduced HepG2 cell line.
Using recombinant retroviral expression, a HepG2 cell line which stably and constitutively expresses the coding sequences of the human cytochrome P4502E1 was previously established. Addition of ethanol (2 to 100 mM) to the culture medium of this cell line for two days resulted in an increase in the content of P4502E1 as determined by immunoblotting and an increase in HepG2 microsomal oxidation of p-nitrophenol, aniline, and N,N-dimethylnitrosamine. The ethanol-induced increase in microsomal oxidation of these substrates was prevented by ligands and inhibitors of P4502E1 as well as anti-human P4502E1 IgG and corresponded to the increase in P4502E1 content. Several other agents including pyrazole, 4-methylpyrazole, isoniazid, pyridine, and DMSO also increased the content of P4502E1 in this cell line but not oxidation of substrates, presumably a reflection of remaining tightly bound to the active site of P4502E1. Slot blot analysis indicated that ethanol addition did not increase P4502E1 mRNA levels. These results indicate that ethanol can increase the content of P4502E1 as well as catalytic oxidation of substrates dependent on P4502E1 in this experimental model, perhaps by stabilization of the protein against degradation.
Blotting, Western↗
Effects of adenosine on paroxysmal atrial tachycardia.
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Adenosine Triphosphate↗
Ionic currents evoked by acetylcholine in isolated acinar cells of the guinea pig nasal gland.
The patch-clamp whole cell recording was used to demonstrate activation of membrane conductance to K+, Cl- and cations induced by acetylcholine (ACh) in the isolated acinar cells of the guinea pig nasal gland. A small outward K+ current at 0 mV and a large transient and sustained inward current at -90 mV were evoked by ACh and ACh-evoked reversal potential was about -3 mV nearly to Cl- equilibrium potential in 140 mM KCl in the pipette and physiological saline in the bath. The ionic substitutional experiments indicated that ACh-evoked inward currents were carried by both Cl- and cations. Both outward and inward currents evoked by ACh were almost completely abolished by removal of external Ca2+ and mimicked those evoked by a calcium ionophore A23187. These findings indicate that ACh-evoked membrane conductances are mediated by an increase in intracellular Ca2+.
Acetylcholine↗
The effects of adenosine on idiopathic ventricular tachycardia.
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Adenosine Triphosphate↗
Electrophoretically mediated micro-assay of alkaline phosphatase using electrochemical and spectrophotometric detection in capillary electrophoresis.
Electrophoretically mediated micro-assays of alkaline phosphatase (ALP) are demonstrated in capillary electrophoretic systems using both electrochemical (ED) and spectrophotometric (UV) detection. In the ED mode, p-aminophenylphosphate was used as the substrate and p-aminophenol (pAP) was monitored at a carbon fiber electrode held at +180 mV vs. Ag/AgCl. Spectrophotometric detection was achieved using the substrate p-nitrophenylphosphate, and monitoring the product p-nitrophenol (pNP) at 405 nm. The detection limit for pAP by ED was determined to be 100-fold lower than for pNP using UV detection. In the determination of ALP, both methods were found to be linear. The detection limit for ALP using zero potential assays with UV detection was determined to be 1.8.10(-6) mg/ml compared to 1.8.10(-7) mg/ml using ED.
Alkaline Phosphatase↗
Ceramide regulates oxidant release in adherent human neutrophils.
We investigated the role of sphingolipids in regulating oxidant release in adherent human neutrophils. Stimulation of adherent neutrophils with formyl-Met-Leu-Phe (fMLP) resulted in the accumulation of ceramide at a time when H2O2 release is terminated. H2O2 release in fMLP-stimulated neutrophils was suppressed in a concentration-dependent manner by the exogenous addition of several free sphingoid amines and short chain ceramides. Sphingosine, dihydrosphingosine, phytosphingosine, N-acetylsphingosine, and N-acetylphytosphingosine, but not N-acetyldihydrosphingosine, inhibited formyl peptide-stimulated oxidant release. The half-maximal inhibitory concentrations of N-acetylsphingosine and N-acetylphytosphingosine were 0.51 and 0.38 microM, respectively. Sphingosine, dihydrosphingosine, and phytosphingosine were less potent inhibitors with half-maximal inhibitory concentrations of 1.78, 15.4, and 1.48 microM, respectively. The 4 beta-phorbol 12 beta-myristate 13 alpha-acetate-induced respiratory burst was inhibited by 5 microM of sphingosine but not by 5 microM of N-acetylsphingosine. The effects of N-acetyl-conjugated sphingols (C2 ceramides) on phosphatidylcholine-specific phospholipase D and phosphatidic acid phosphohydrolase were markedly different from the effects of the related sphingoid bases. Both C2 ceramides and sphingoid bases partially inhibited the diradylglycerol formation by the phosphatidylcholine-specific phospholipase D pathway. Under the same conditions, however, N-acetyldihydrosphingosine and dihydrosphingosine failed to suppress H2O2 release in fMLP-stimulated neutrophils. These findings demonstrate that C2 ceramides inhibit H2O2 generation in fMLP-stimulated neutrophils via protein kinase C- or sphingoid base-independent mechanisms. The effect of ceramide in inhibiting the respiratory burst is structurally specific, because either a 4,5-trans double bond or 4-hydroxyl group is required for the inhibition. Therefore, ceramides may regulate oxidant release in adherent neutrophils.
Cell Adhesion↗
Activation of phospholipase C beta 4 by heterotrimeric GTP-binding proteins.
Transient transfection assays were used to determine how the activity of phospholipase C beta 4, which is preferentially expressed in retina, was regulated. An expression vector carrying the full-length cDNA corresponding to phospholipase C beta 4 was constructed and co-transfected into COS-7 cells together with cDNA encoding the alpha subunits of the Gq class and various beta and gamma subunits corresponding to the heterotrimeric GTP-binding proteins. We found that all the alpha subunits of the Gq class, including G alpha q, G alpha 11, G alpha 14, G alpha 15, and G alpha 16 could activate PLC beta 4 and that none of the G beta gamma subunits that we tested including G beta 1 gamma 1, G beta 1 gamma 2, G beta 1 gamma 3, or G beta 2 gamma 2 activated phospholipase C beta 4. In control experiments, cotransfection with cDNA encoding the alpha subunit of transducin or Gi2 gave no activation of PLC beta 4. These results indicate that phospholipase C beta 4 is activated by G alpha subunits that are members of the Gq class, and, like the phospholipase C beta 1 isoform, it is refractory to activation in the transfection assay by many of the combinations of beta and gamma subunits found in the heterotrimeric G-proteins.
Amino Acid Sequence↗
Characteristics and radiofrequency ablation therapy of intermediate septal accessory pathway.
Fourteen patients (5%) with an intermediate septal accessory pathway were identified among 283 consecutive patients with the Wolff-Parkinson-White syndrome who had electrophysiologic study and radiofrequency ablation therapy. Nine were women and 5 were men (mean age 33 +/- 13 years). The resting electrocardiogram showed ventricular preexcitation in 8 patients and normal PR interval in 6. Anterograde and retrograde mapping studies revealed that the accessory pathway was para-Hisian in 11 patients and paranodal in 3. The accessory pathway was successfully ablated in 10 patients (9 para-Hisian and 1 paranodal) and damaged in 1 (para-Hisian). Treatment of 3 patients was complicated by transient atrioventricular (AV) block, of 1 by intermittent second-degree AV block, and of another by permanent complete AV block requiring implantation of a permanent pacemaker. Six patients underwent a follow-up electrophysiologic study 84 +/- 55 days after ablation; none had induction of tachycardia even after isoproterenol infusion. It is concluded that radiofrequency ablation therapy for intermediate septal accessory pathway is feasible. However, the success rate is only modest (71%), whereas complications with heart block (36%) or complete right bundle branch block (29%) are high. Thus, the procedure should be reserved for patients with life-threatening or troublesome symptomatic tachyarrhythmias.
Adolescent↗
Estimation of pulmonary artery pressure from pulmonary vein wedge pressure.
Correlations between pulmonary artery and pulmonary vein wedge pressures were investigated in 13 patients with atrial septal defect and 1 patient with Tetralogy of Fallot. Pulmonary vein wedge pressure wave form resembled that of pulmonary artery pressure, and the former lagged behind the latter by 70 to 110 msec (mean 88 +/- 14) as observed by the fluid-filled catheter system. Diastolic pulmonary artery and diastolic pulmonary vein wedge pressures were nearly identical. Although systolic and mean pulmonary artery pressures correlated well with respective pulmonary vein wedge pressures, there were discrepancies when systolic and mean pulmonary artery pressure exceeded 35 and 20 mm Hg, respectively. However, systolic and mean pulmonary artery pressures could be estimated by adding the difference between the diastolic pulmonary vein wedge pressure and the mean left atrial pressure to corresponding systolic or mean pulmonary artery pressure. In conclusion, pulmonary artery pressures can be estimated by measuring pulmonary vein wedge pressures and the mean left atrial pressure.
Adult↗
Ciliary neurotrophic factor combined with soluble receptor inhibits synthesis of proinflammatory cytokines and prostaglandin-E2 in vitro.
In human peripheral blood mononuclear cells, ciliary neurotrophic factor (CNTF) weakly suppressed endotoxin-induced interleukin (IL)-1 and prostaglandin E2(PGE2). Suppression of PGE2 and IL-8 synthesis was significantly greater (up to 42.6%, P < 0.05) by adding a 10-fold molar excess of soluble CNTF receptor (sCNTFR alpha). In cultured human fibroblasts, CNTF at 12 micrograms/ml did not suppress IL-1 alpha-induced IL-8. However, in the presence of a 10-fold excess of sCNTFR alpha, 300 ng/ml of CNTF suppressed IL-1 alpha-induced IL-8 by 44%. Therefore, sCNTFR alpha can confer to CNTF anti-inflammatory properties in vitro. IL-6 which, like CNTF, utilizes the gp130 signal transducer, possesses similar inhibitory effects. That CNTF and IL-6 share gp130 as a receptor component suggests that gp130 mediates these anti-inflammatory responses.
Cells, Cultured↗
Effects of estrogen replacement on the relative levels of choline acetyltransferase, trkA, and nerve growth factor messenger RNAs in the basal forebrain and hippocampal formation of adult rats.
Previous studies have shown that estrogen replacement can significantly affect the expression of choline acetyltransferase immunoreactivity (ChAT-IR) and low-affinity (p75NGFR) nerve growth factor receptors within cholinergic neurons located in specific regions of the basal forebrain. To extend this work, we have examined the effects of estrogen replacement on relative levels of choline acetyltransferase (ChAT), trkA, and nerve growth factor (NGF) mRNAs within different regions of the basal forebrain and hippocampal formation using quantitative in situ hybridization techniques. Ovariectomized Sprague-Dawley rats received continuous estrogen replacement for 2 days, 1 week, or 2 weeks. The data show that estrogen replacement results in significant increases in relative cellular levels of ChAT mRNA in the medial septum (MS) and nucleus basalis magnocellularis (nBM), but not in the horizontal limb of the diagonal band of Broca (HDB) or the striatum. In contrast, estrogen replacement resulted in significant decreases in relative levels of NGF mRNA in the hippocampus and of trkA mRNA in the MS and nBM (but not in the HDB or the striatum). The time-course of these effects is consistent with estrogen having a direct effect on ChAT expression which is followed by indirect effects on trkA. The data are also consistent with previous findings in which estrogen replacement resulted in significant increases in ChAT-IR which were followed by significant decreases in p75NGFR mRNA and protein and then a reduction in ChAT-IR back to control levels. Together, these data indicate that estrogen replacement can have significant effects on basal forebrain cholinergic function, and that some of these effects may be mediated by effects of estrogen replacement on the expression of NGF and NGF receptors.
Animals↗
Successful radiofrequency ablation in reentrant tachycardia incorporating a nodoventricular tract.
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Adolescent↗
Radiofrequency ablation therapy in atypical or multiple atrioventricular node reentry tachycardias.
Electrophysiologic study and radiofrequency ablation therapy were performed in 23 patients with atypical (8 patients) or multiple (15) atrioventricular node reentry tachycardias. Dual pathways with anterograde fast and slow pathway conductions were demonstrated in 16 patients. Studies on retrograde conduction revealed the presence of three different pathways, including fast (15 patients), intermediate (17), and slow (16). The radiofrequency current was applied to the inferior aspect, one-third anterior two-thirds posterior between the His bundle and the ostium of the coronary sinus, of Koch's triangle along the tricuspid annulus in all patients. Application of the current resulted in selective ablation or modification of both retrograde intermediate and slow pathway conductions in 20 patients. In two patients retrograde fast pathway conduction was also modified. Complete atrioventricular block occurred in the remaining patient. Sixteen patients had no induction of tachycardia or echo, 4 had induction of a single echo, and 2 had induction of the slow-fast form tachycardia; one of those 2 patients underwent a second trial and was successful. A median application of 2 was delivered at a power of 25 +/- 5 W and a duration of 18 +/- 4 sec. The total fluoroscopic time was 25 +/- 21 minutes. The anterograde fast pathway conduction was unaffected; the shortest atrial paced cycle length that sustained 1:1 fast pathway conduction was 329 +/- 65 msec and 330 +/- 68 msec before and after ablation, respectively. A follow-up electrophysiologic study was performed in 16 patients 60 +/- 15 days after ablation. Eleven had no induction of tachycardia or echo, and five had induction of < 3 echoes. This study demonstrated that radiofrequency ablation with the inferior approach is effective and safe in atypical or multiple atrioventricular node reentry tachycardias. It resulted in ablation of the slow pathway and retrograde intermediate pathway conduction with preserved atrioventricular conduction.
Adult↗
Late clinical and electrophysiologic outcome of radiofrequency ablation therapy by the inferior approach in atrioventricular node reentry tachycardia.
A late electrophysiologic study was conducted in 182 of 289 patients with slow-fast atrioventricular node reentry tachycardia 81 +/- 36 days after radiofrequency ablation therapy by the inferior approach. Of these 182 patients, electrophysiologic study immediately after ablation revealed a selective modification of the slow pathway in 159, a modification of both the slow and fast pathways in 15, a modification of the fast pathway alone in 3, and failure of ablation in 5. One hundred two patients had no induction of echoes; 75 had induction of fewer than four echoes; and 5 had induction of sustained tachycardia with or without isoproterenol infusion. The late electrophysiologic study in these 182 patients revealed a persistent effect without changes in conduction properties in 161 (88%) patients. A change in conduction properties was noted in 21 patients, including 5 with resumption of slow- or fast-pathway conduction with induction of sustained tachycardia, 8 with improved fast- or slow-pathway conduction, and 8 with an additional depression of fast- or slow-pathway conduction. Of the 102 patients with no induction of echoes and the 75 patients with induction of fewer than four echoes during the immediate postablation electrophysiologic study, 5 (3 and 2, respectively) patients had induction of tachycardia. Of the 5 patients with induction of sustained tachycardia in the immediate postablation electrophysiologic study, 3 continued to have induction of sustained tachycardia; 1 had induction of echoes only; and 1 had no induction of echoes.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Double loop figure-of-8 reentry as the mechanism of multiple atrioventricular node reentry tachycardias.
Seven patients with multiple atrioventricular node reentry tachycardia were analyzed to unravel the mechanism of these tachycardias. Six of the seven patients showed anterograde dual atrioventricular node pathways and one showed anterograde conduction through the fast pathway. Three types of retrograde pathways were noted among these seven patients: (1) the fast pathway with the earliest atrial activation at the His bundle area; (2) the intermediate pathway with the earliest atrial activation at the ostium of the coronary sinus; and (3) the slow pathway with the earliest atrial activation at the ostium of the coronary sinus. All seven patients used the intermediate pathway for retrograde conduction. However, one patient showed evidence of retrograde slow pathway conduction with demonstrable retrograde dual pathways, and another showed evidence of retrograde fast pathway conduction with a shift of atrial activation sequence when conduction switched to the intermediate pathway. Four different types of reentry circuits using either the fast or the slow pathway as the anterograde limb and one of the three retrograde pathways as the retrograde limb were demonstrated in these seven patients, resulting in two types of tachycardias in four patients and three types of tachycardias in three patients. A change in tachycardia type could be induced with atrial or ventricular stimulation. A radiofrequency current delivered to the inferior aspect of Koch's triangle along the tricuspid anulus in five patients resulted in selective ablation or modification of the intermediate pathway or the slow pathway, with preservation of anterograde atrioventricular conduction and abolition of tachycardias. The findings suggest that a double loop figure-of-8 reentry circuit including a fast pathway, a slow pathway, and an intermediate pathway is responsible for multiple atrioventricular node reentry tachycardias.
Adult↗
A simulation study of external counterpulsation.
To study the haemodynamic effect of external counterpulsation, a computer model has been extended based on our previous work. Using this model, computer simulations have been performed on following aspects: the relationship between blood flow distributions and the control scheme; counterpulsation with and without buttock balloons; effects of duration and time intervals for sequential pulsing; and the potential to use a performance index for the optimal control of this assist device to the failing heart. The results indicate that effective assistance can be achieved by a proper setting of the control scheme. The results also show that this device is effective to improve the circulation status of other organs in addition to the heart. Simulation results agree well with the clinical data.
Abdomen↗