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Biomedical subjects

W Hua

Publications and source records attributed to W Hua.

30 records · Page 2Linked to original sources

Estrogen action in human ovarian cancer.

Evidence is accumulating for a facilitative role for estrogen in ovarian cancer. Although response to antiestrogen therapy has been poor, there is a distinct subset of patients that respond. Strategies for treatment of ovarian cancer would be improved by identification of patients likely to respond to hormonal therapy. Cell culture models that are responsive or resistant to estrogen and antiestrogen may be of value in finding markers that predict responsiveness to hormonal therapy. Several model cell lines have been generated that express ER and proliferate in response to estrogen in vitro. Further studies are needed to better characterize the response of these ER positive cells lines to estrogen in vivo in mouse xenograft models. Expression of many of the same genes are regulated by estrogen in breast and in ovarian cancer cell lines. One exception may be the HER-2/neu oncogene product, which is down-regulated by estrogen in responsive breast carcinoma cells but not in two ovarian carcinoma cell lines. Initial analyses of several estrogen responsive and one resistant cell model suggests the potential value of progesterone receptor presence and low levels of HER-2/neu expression for predicting responsiveness to hormonal therapy. Additional cell models need to be investigated to determine the frequency with which these markers are associated with antiestrogen resistance.

Animals↗

Chronic steroid-eluting lead performance: a comparison of atrial and ventricular pacing.

It is generally believed that atrial pacing leads have higher stimulation thresholds and long-term complication rates than ventricular leads, and this is one of the factors limiting the use of dual chamber pacing. A study was undertaken to compare atrial and ventricular bipolar tined steroid-eluting leads in two designs: the Medtronic CapSure SP and the Telectronics Encor Dec. There were 123 pairs of leads: 81 CapSure SP and 42 Encor Dec. Bipolar atrial and ventricular stimulation thresholds, electrograms, and pacing impedance were measured using the Telectronics META DDDR pulse generator immediately postimplantation, and at 1, 3, and 6 months for all leads and at 12, 18, and 24 months for the CapSure SP. The only major lead complication was a 2% atrial lead dislodgment rate. All leads demonstrated low stimulation thresholds, with the CapSure SP leads having lower values than comparable Encor Dec leads. All leads had a mean range of 0.53-0.89 V at all testing periods with P < 0.05 for atrial leads only. There were no differences in electrogram size between manufacturers and no instances of atrial and ventricular undersensing. Pacing impedance was about 100 omega higher for the Encor Dec leads (P < 0.05, atrial leads only), suggesting that these leads will result in lower pacing energy losses provided the pulse generators are at identical settings. More than 90% of patients could be paced chronically in the atrium and ventricle at 2.5 V, but for chronic 1.6-V pacing, the CapSure SP leads were superior. In conclusion, atrial and ventricular steroid-eluting leads of both manufacturers gave excellent stimulation threshold results allowing low energy dual chamber pacing.

Aged↗

Long-term performance of steroid-eluting lead in dual chamber pacing.

The atrial pacing lead is believed having higher stimulation thresholds and long-term complication rates than ventricular lead, this being one of the factors limiting the use of dual chamber pacing. A prospective study was undertaken to evaluate both atrial and ventricular bipolar tined steroid-eluting leads in long-term dual chamber pacing. There are 81 pairs of leads (Medtronic Capsure SP) used in 81 patients. Bipolar atrial and ventricular stimulation thresholds were measured immediately post implantation and 1, 3, 6, 12, 18 and 24 months. All leads demonstrated low mean stimulation thresholds during the follow-up and more than 94% of leads could be paced chronically in the atrium and ventricle at 2.5 volts. In conclusion, atrial and ventricular steroid-eluting leads gave excellent stimulation thresholds allowing low energy long-term dual chamber pacing.

Aged↗

Radiofrequency ablation of idiopathic ventricular tachycardia.

BACKGROUND: Radiofrequency ablation (RFA) has been shown to be very effective in the treatment of supraventricular tachycardias and has replaced surgical ablation. Only a few reports of RFA for idiopathic ventricular tachycardia (VT) have appeared in the literature during the last two years. AIM: This paper presents our experience with RFA for idiopathic VT in 19 patients. MATERIAL: The age range of patients was 22-60, with a mean of 37.9 years. Twelve out of 19 were females, two patients had cardiac failure due to almost incessant VT while the rest had normal left ventricular function. Twelve patients had VT arising from the right ventricle (RV); of these, nine were from the outflow tract, two from the RV apex, and one from the mid-anterior RV. Seven patients had VT arising from the left ventricle (LV); of these, five were from the inferobasal portion of the septum and two were from the anterolateral area. METHODS: In all patients the diagnostic study and therapeutic RFA were combined in a single procedure. Pacemapping was used to guide the site of RFA in patients with VT arising from the RV. Local activation time (LAT), Purkinje potentials (PP) and pacemapping were used to guide RFA in those patients with LV septal tachycardias. RESULTS: A total of 21 RF procedures were performed in 19 patients and 15 out of 19 patients had successful VT ablation. Ten of the 12 patients with RV tachycardias and all five patients with LV septal (left axis, right bundle branch block) tachycardias were successfully ablated. One patient with mid anterior RV VT required two attempts for successful ablation. One patient with RV outflow tract (RVOT) VT could not be ablated despite two attempts. Two patients with LV tachycardias arising from the antero-lateral LV could also not be ablated. During a follow up period of two to 16 months none of the successful patients had recurrence of VT. The number of RF applications was one to 27, mean 10; fluoroscopy times were four to 75, mean 26.9 minutes. CONCLUSION: Idiopathic VT frequently arises from the RVOT and inferobasal portion of the LV septum. These tachycardias can be diagnosed on clinical and ECG grounds. RFA for idiopathic VT arising from these areas has a high success rate and this mode of treatment should be considered as a nonpharmacological curative treatment for symptomatic patients.

Adolescent↗

Developmentally expressed Ca(2+)-sensitive adenylyl cyclase activity is disrupted in the brains of type I adenylyl cyclase mutant mice.

The type I Ca(2+)-sensitive adenylyl cyclase has been implicated in several forms of synaptic plasticity in vertebrates. Mutant mice in which this enzyme was inactivated by targeted mutagenesis show deficient spatial memory and altered long term potentiation (Wu, Z. L., Thomas, S. A., Villacres, E. C., Xia, Z., Simmons, M. L., Chavkin, C., Palmiter, R. D., and Storm, D. R. (1995) Proc. Natl Acad Sci. U. S. A. 92, 220-224). Long term potentiation in the CA1 region of the rat hippocampus develops during the first 2 weeks after birth and reaches maximal expression at postnatal day 15 with a gradual decline at later stages of development. Here we report that Ca(2+)-stimulated adenylyl cyclase activity in rat hippocampus, cerebellum, and cortex increases significantly between postnatal days 1-16. This increase appears to be due to enhanced expression of type I adenylyl cyclase rather than type VIII adenylyl cyclase, the other adenylyl cyclase that is directly stimulated by Ca2+ and calmodulin. Type I adenylyl cyclase mRNA in the hippocampus increased 7-fold during this developmental period. The developmental expression of Ca(2+)-stimulated adenylyl cyclase activity in mouse brain was attenuated in mutant mice lacking type I adenylyl cyclase. Changes in expression of the type I adenylyl cyclase during the period of long term potentiation development are consistent with the hypothesis that this enzyme is important for neuroplasticity and spatial memory in vertebrates.

Adenylyl Cyclases↗

SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth-resistant to estrogen and antiestrogens.

Estrogen receptor positive ovarian cancer is often refractile to antiestrogen therapy. Here we describe the SKOV3 human ovarian carcinoma cell line as an in vitro model for estrogen and antiestrogen resistant ovarian cancer. While SKOV3 cells expressed estrogen receptor (ER) mRNA and protein at a similar level as the estrogen responsive T47D breast carcinoma cell line, their growth was not responsive to estradiol (E2) and was not inhibited by the antiestrogens OH-tamoxifen and ICI 164,384. The ER in SKOV3 cells was normal with respect to apparent Kd for binding with E2, E2 regulation of a transiently transfected ERE driven reporter gene, and E2 stimulation of expression of the early growth response genes c-myc and c-fos. However, the SKOV3 cells exhibited no expression of the progesterone receptor gene (PR) even after addition of E2, and the protein products of the estrogen responsive genes HER-2/neu and cathepsin D were expressed at constitutive levels that were not regulated by E2. Therefore, estrogen resistance in these cells may be a result of constitutive expression and loss of E2 regulation of selected growth regulatory gene products rather than a defect in estrogen activation of ER as a transcriptional regulator.

Blotting, Northern↗

Atrial pacing leads: the clinical contribution of steroid elution.

Although the original atrial pacing leads were passive fixation and J shaped for right atrial appendage placement, the subsequent development of the active fixation screw-in lead found favor because of a perceived low incidence of lead dislodgment and a wider selection of atrial pacing sites. A bipolar atrial lead study was undertaken to compare the long-term atrial implant data in 215 patients. Study leads comprised one passive fixation, steroid-eluting lead (Medtronic CapSure SP, 119 patients) and three nonsteroid-eluting leads; two active fixation (Medtronic BISPING model 4058, 30 patients; and Telectronics ACCUFIX model 330-801, 44 patients) and one passive fixation (Telectronics ENCOR model 330-854, 22 patients). Bipolar atrial voltage stimulation thresholds and electrograms were measured using the Telectronics META DDDR immediately postimplantation, and at 1-, 3-, 6-, 12-, and 18-month follow-up. There were 135 males and the mean age 68 years. The incidence of lead dislodgment was 4% for active fixation and 2% for passive fixation. All nonsteroid leads showed a typical rise in stimulation threshold with the highest being the ACCUFIX followed by the BISPING and ENCOR. The steroid-eluting CapSure SP, however, demonstrated a flat response with 98% of leads at 18 months having a value < or = 1.3 volts allowing voltage programming to 2.5 volts (2:1 safety ratio). Telemeted electrograms showed no differences for all leads at all visits. For low voltage atrial pacing with a low incidence of dislodgment and satisfactory atrial sensing, the steroid-eluting passive fixation lead is superior to all nonsteroid-eluting leads.

Aged↗

[The pathologic myocardial change caused by intracoronary ethyl alcohol injection and its mechanism].

Intracoronary chemical injection to ablate ventricular tachycardia is a new method. Through experiments in 22 dogs, we studied the pathologic change of the myocardium and its mechanism following intracoronary injection of 96% ethyl alcohol. All dogs receiving ethyl alcohol injection displayed myocardial necrosis, and most of them presented thrombus in the coronary branch. The pathologic change in the acute period may have resulted from direct ethyl alcohol damage, and that in the late period may have resulted from both direct damage and thrombus caused by arterial damage.

Animals↗

Electrophysiologic follow-up in dogs receiving intracoronary ethyl alcohol injection.

96% ethyl alcohol was injected into a diagonal branch of the left anterior descending coronary artery of 10 out of 12 anesthetized dogs, and saline solution was injected in the remaining 2. After chest closure, the dogs were subjected to ambulatory monitoring (H) during days 1, 2, 3 and 7. The electrophysiologic study (EPS) and signal-averaged electrocardiography. (SA-ECG) were performed before the injection and again at day 7 after injection. H failed in one dog which died of ventricular fibrillation. In the other 9 dogs that received alcohol injection, H showed frequent ventricular premature and ventricular tachycardia (VT) after injection; six of the 9 dogs sustained VT, which was not inducible by EPS. VT was not found in 2 control dogs receiving saline solution injection. The SA-ECG showed no ventricular late potentials in dogs receiving alcohol injection. Post-ablation ventricular arrhythmia (including VT) occurred after intracoronary ethyl alcohol injection in all dogs. Arrhythmogenicity markedly declined during the first 3 days and almost completely disappeared on day 7 after ablation. There was no evidence in favor of reentry as the mechanism of these arrhythmias. Enhanced automaticity was considered as the mechanism for ventricular arrhythmia.

Animals↗

[The experimental ablation of ventricular tachycardia in dogs with intracoronary ethyl alcohol injection].

In 15 anesthetized dogs, a diagonal branch of the left anterior descending coronary artery was cannulated. Localized ventricular tachycardia (VT) was induced by injecting aconitine solution into the left ventricular wall perfused by the cannulated diagonal branch. In 6 untreated control dogs, VT lasted 17.6 +/- 8.3 minutes, 3 of them degenerated into ventricular fibrillation. The VTs were eliminated in 8 of the 9 dogs (88.9%) 1.2 +/- 1.4 minutes after injection of 96% ethyl alcohol. The pathologic examination revealed that transmural myocardial necrosis was present in 7 of 9 dogs receiving alcohol injection. Fibrin or thrombus was present in the diagonal coronary branch in 5 dogs. The conclusion was that the intracoronary injection of 96% ethyl alcohol ablated aconitine-induced ventricular tachycardia effectively. This approach may become a promising new method to treat ventricular tachycardia or other arrhythmia.

Aconitine↗