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Biomedical subjects

W Quan

Publications and source records attributed to W Quan.

At least 19 recordsLinked to original sources

Neurogenesis, migration, and apoptosis in the vomeronasal epithelium of adult mice.

The location of neurogenesis and the direction of migration of neurons in the adult mouse vomeronasal organ is controversial. Cell division occurs at the center, and particularly, at the edges of the epithelium. Newly generated cells at the center of the epithelium participate in neurogenesis, however, it is unknown to what extent dividing cells at the edges participate in growth, become apoptotic or mature into neurons. Premitotic cells were labeled with bromodeoxyuridine (BrdU) in adult mice and animals allowed to survive for different postinjection periods. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end-labeling (TUNEL) method was used to show the distribution of apoptotic cells. The vertical and horizontal position of BrdU-labeled cells was analyzed as a function of postinjection survival time. Vertical and horizontal migration of BrdU-labeled cells were detected. Cells in the central portions of the epithelium migrated vertically to become neurons as demonstrated by co-expression of olfactory marker protein. Cells at the edges migrated horizontally very slowly (less than 10% of the distance from the edge to the center of the epithelium per month), thus indicating that these cells participate in cell renewal exclusively in marginal regions. Neural turnover in the mouse vomeronasal epithelium, therefore appears to occur through a process of vertical migration. Data on the distribution of apoptotic cells indicate that a number of dividing cells throughout the epithelium, but particularly at the edges, die before becoming functional neurons. Accordingly, most dividing cells at the edges probably constitute a reservoir of stem cells dying before differentiation.

Animals↗

Fetal mitochondrial heart and skeletal muscle damage in Erythrocebus patas monkeys exposed in utero to 3'-azido-3'-deoxythymidine.

3'-azido-3'-deoxythymidine (AZT) is given to pregnant women positive for the human immunodeficiency virus type 1 (HIV-1) to reduce maternal-fetal viral transmission. To explore fetal mitochondrial consequences of this exposure, pregnant Erythrocebus patas monkeys were given daily doses of 1.5 mg (21% of the human daily dose) and 6.0 mg (86% of the human daily dose) of AZT/kg body weight (bw), for the second half of gestation. At term, electron microscopy of fetal cardiac and skeletal muscle showed abnormal and disrupted sarcomeres with myofibrillar loss. Some abnormally shaped mitochondria with disrupted cristae were observed in skeletal muscle myocytes. Oxidative phosphorylation (OXPHOS) enzyme assays showed dose-dependent alterations. At the human-equivalent dose of AZT (6 mg of AZT/kg bw), there was an approximately 85% decrease in the specific activity of NADH dehydrogenase (complex I) and three- to sixfold increases in specific activities of succinate dehydrogenase (complex II) and cytochrome-c oxidase (complex IV). Furthermore, a dose-dependent depletion of mitochondrial DNA levels was observed in both tissues. The data demonstrate that transplacental AZT exposure causes cardiac and skeletal muscle mitochondrial myopathy in the patas monkey fetus.

Animals↗

An association between anxiety and neurocardiogenic syncope during head-up tilt table testing.

To study the association between anxiety and neurocardiogenic syncope as determined by head-up tilt table testing (HUT) in men and women with presyncope or syncope, patients with unexplained syncope or presyncope undergoing HUT were asked to complete the Burns Anxiety Inventory (BAI), a validated inventory of 33 questions with responses graded from 0 to 3. HUT consisted of a 30-minute tilt to 60 degrees, which if negative, was repeated with an isoproterenol infusion. A positive HUT was defined as symptomatic hypotension and/or bradycardia. Of the 66 patients who completed the BAI and underwent HUT, 33 were men and 33 were women. The mean age was 57 +/- 18 years (17-91 years). Patients with a positive HUT had a higher BAI score than those with a negative HUT (22 +/- 12 vs 14 +/- 13, P = 0.017). This association was stronger in women with a BAI score of 24 +/- 11 in those with a positive HUT versus 13 +/- 8 in those with a negative HUT (P = 0.005). In contrast, the mean BAI score for men with a positive HUT was 19 +/- 13, as compared to 15 +/- 16 for a negative HUT (P = 0.5). In conclusion, the present study demonstrates a statistical association between anxiety (as determined by BAI) and HUT result. Gender-based analysis revealed a more statistically significant relationship between anxiety and HUT outcome for women as compared to men.

Adult↗

The effects of intrinsic sympathomimetic activity on beta-blocker efficacy for treatment of neurocardiogenic syncope.

To compare the efficacy and side effects of beta-blockers with intrinsic sympathomimetic activity (ISA) to those without ISA, we retrospectively reviewed patients diagnosed with neurocardiogenic syncope (NCS) as determined by head-up tilt table testing. Four hundred and thirty-one patients (mean age of 57 +/- 25 years) underwent head-up tilt table testing for syncope of unknown etiology, of which 120 patients were diagnosed with NCS; 87 of these patients were treated with beta-blocker therapy. Only 56 patients could be contacted during follow-up. Twenty-eight patients were treated with beta-blockers with ISA (acebutolol or pindolol) and 28 received beta-blockers without ISA (atenolol or metoprolol) based on physician preference and followed for up to 2 years. During the follow-up period, beta-blockers with or without ISA had comparable clinical efficacy in suppressing recurrent syncope in patients with NCS. However, beta-blockers with ISA were better tolerated and caused less fatigue (32% side effects) as compared to those without ISA (50% side effects; p = 0.23). The benefits of beta-blockers with ISA were more pronounced in patients less than 60 years old (19% side effects with beta-blocker with ISA as compared to 85% side effects with beta-blocker without ISA; p = 0.0004). Beta-blockers without ISA appear to be better tolerated and caused less fatigue in patients 65 years old or greater (20%) than in patients less than 65 years old (85%; p = 0.0002).

Acebutolol↗

[Digital subtraction angiography of cerebrum for diagnosis of cavernous sinus fistula and its intravascular treatment].

OBJECTIVE: To evaluate the diagnosis of digital subtraction angiography (DSA) of cerebral arteries and the intravascular treatment for carotid artery-cavernous sinus fistula (CCF) mainly manifesting as pulsating exophthalmos. METHODS: Digital subtraction angiography (DSA) of cerebral arteries was carried out for 15 patients with pulsating exophthalmos. Of them, detectable balloon and tungsten filament microcoil were used for intravascular embolism treatment in 12 cases, and the 3 cases with CCF of the branch of external carotid artery were not treated. RESULTS: Of the 15 cases, 12 were fallen in the CCF of high flow type of unilateral internal carotid artery, and 3 in the CCF of low flow type of unilateral external carotid artery. The symptoms and signs of intravascular embolism disappeared after treatment in 11 cases. CONCLUSION: Cerebral artery DSA and intravascular therapy are the ideal methods for the diagnosis and treatment of CCF mainly manifesting as pulsating exophthalmos.

Adult↗

Efficient integration of a realistic two-dimensional cardiac tissue model by domain decomposition.

The size of realistic cardiac tissue models has been limited by their high computational demands. In particular, the Luo-Rudy phase II membrane model, used to simulate a thin sheet of ventricular tissue with arrays of coupled ventricular myocytes, is usually limited to 100 x 100 arrays. We introduce a new numerical method based on domain decomposition and a priority queue integration scheme which reduces the computational cost by a factor of 3-17. In the standard algorithm all the nodes advance with the same time step delta t, whose size is limited by the time scale of activation. However, at any given time, many regions may be inactive and do not require the same small delta t and consequent extensive computations. Hence, adjusting delta t locally is a key factor in improving computational efficiency, since most of the computing time is spent calculating ionic currents. This paper proposes an efficient adaptive numerical scheme for integrating a two-dimensional (2-D) propagation model, by incorporating local adjustments of delta t. In this method, alternating direction Cooley-Dodge and Rush-Larsen methods were used for numerical integration. Between consecutive integrations over the whole domain using an implicit method, the model was spatially decomposed into many subdomains, and delta t adjusted locally. The Euler method was used for numerical integration in the subdomains. Local boundary values were determined from the boundary mesh elements of the neighboring subdomains using linear interpolation. Because delta t was defined locally, a priority queue was used to store and order next update times for each subdomain. The subdomain with the earliest update time was given the highest priority and advanced first. This new method yielded stable solutions with relative errors less than 1% and reduced computation time by a factor of 3-17 and will allow much larger (e.g., 500 x 500) models based on realistic membrane kinetics and realistic dimensions to simulate reentry, triggered activity, and their interactions.

Action Potentials↗

Implantable Cardioverter-Defibrillator Implantation in the Electrophysiology Laboratory by Electrophysiologists.

Recent developments in implantable cardioverter-defibrillator (ICD) technology have helped simplify the surgical implantation technique of these devices. There has been a marked reduction in the size of these devices making them easier to implant pectorally. In addition ICDs have enhanced longevity and a more facile transvenous lead system. Surgical implantation is almost identical to the procedure used for permanent pacemaker implantation in conjunction with the performance of a short electrophysiologic/arrhythmia induction protocol. In general, the average implant time is approximately one hour and in our series minimal morbidity and no mortality was identified. In conclusion, ICDs can be safely and effectively implanted in the electrophysiology laboratory by electrophysiologists in a timely and cost-effective manner. These implant procedures can help to shorten the length of stay and improve the operating room utilization for more critical procedures.

Journal Article↗

Nonlinear dynamics in ventricular fibrillation.

Electrogram recordings of ventricular fibrillation appear complex and possibly chaotic. However, sequences of beat-to-beat intervals obtained from these recordings are generally short, making it difficult to explicitly demonstrate nonlinear dynamics. Motivated by the work of Sugihara on atmospheric dynamics and the Durbin-Watson test for nonlinearity, we introduce a new statistical test that recovers significant dynamical patterns from smoothed lag plots. This test is used to show highly significant nonlinear dynamics in a stable canine model of ventricular fibrillation.

Algorithms↗

Transforming growth factor beta 1 suppresses genomic instability independent of a G1 arrest, p53, and Rb.

Alterations in expression of or responsiveness to transforming growth factor beta (TGF-beta) are frequently found in human and animal epithelial cancers and are though to be important for loss of growth control in the neoplastic cell. We show here that keratinocyte cell lines from mice with a targeted deletion of the TGF-beta 1 gene have significantly increased frequencies of gene amplification in response to the drug N-phosphonoacetyl-L-aspartate (PALA) compared to TGF-beta 1-expressing control keratinocyte cell lines. In contrast to the control lines, the PALA-mediated G1 arrest did not occur in the TGF-beta 1 null keratinocytes despite the presence of wild-type p53 in both genotypes. Exogenous TGF-beta 1 suppresses gene amplification in the null keratinocytes at concentrations that do not cause a G1 growth arrest and in human tumor cell lines that are insensitive to TGF-beta 1-mediated growth inhibition. The pathway of TGF-beta 1 suppression is independent of the p53 and Rb genes, but requires an intact TGF-beta type II receptor. These studies reveal a novel TGF-beta-mediated pathway regulating genomic stability and suggest that defects in TGF-beta signaling may have profound effects on tumor progression independent of cell proliferation.

Animals↗

Development of an interactive computer-guided method for radiofrequency catheter ablation of ventricular tachycardia.

The purpose of this study was to develop a simple computer-guided approach to localizing ventricular tachycardias during ventricular mapping. Six patients with sustained monomorphic ventricular tachycardia were connected to a 32-lead computer body surface mapping system. Isoarea maps of induced ventricular tachycardia were recorded. Then a pacing probe was placed in either the right or left ventricle, and maps were generated from a variety of sites. Differences between ventricular tachycardia and pace map maxima X, Y coordinates were utilized to guide catheter manipulation and localization. In 6 of 6 patients (100%) this method appeared to provide a systematic approach to ventricular tachycardia localization. Computer-generated correlations as well as the X, Y coordinates of the QRS isoarea maxima were used to determine proximity to the ventricular tachycardia foci and direct catheter manipulation. In the next three patients this method was applied prospectively to help guide catheter manipulation during ventricular tachycardia (two right ventricular outflow tract tachycardias, and one left ventricular tachycardia). After a mean of 4.0 +/- 1.7 radiofrequency applications, ventricular tachycardia was no longer inducible, and at 7 +/- 0 months follow-up there have been no arrhythmia recurrences. We conclude that online computerized body surface mapping can assist in localizing ventricular tachycardia. Differences in maxima during pace maps and in-situ ventricular tachycardias can help with catheter manipulation as well as with more precise identification of focal tachycardias. This technique appears to hold the promise of a simple computer-guided method that may facilitate radiofrequency catheter ablation.

Adult↗

Antiemetic therapy in managed care oncology: roundtable discussion.

Few diagnoses are feared more by patients than cancer. In addition to the life-threatening nature of many cancers, the spectre of very difficult the treatment provides patients with little or no level of comfort. However, recent advances in the treatment of the side effects of cancer chemotherapy are helping to change these attitudes. On April 4, 1996, a panel of experts was convened to discuss these issues and how they affect MCOs.

Antiemetics↗

Implantable cardioverter-defibrillator patch shunting effect manifestations on the body surface map.

The purpose of this study was to demonstrate the known shunting effect of implantable cardioverter-defibrillator patches using the body surface map. Using a 32-lead body surface mapping computer system (Corazonix Predictor, Oklahoma City, OK) we recorded body surface potential maps both prior to and 7 days after implantable cardioverter-defibrillator patch placement in a patient during right ventricular pacing at 60 beats/minute. This study demonstrated a marked shunting effect from the patches to the body surface during electrical depolarization as well as repolarization. In addition, patch orientation and configuration were evaluated by this method. Specifically, the waveforms were affected by the presence of insulator patches. This may be an important explanation, which may prevent appropriate transthoracic defibrillation using standard configurations. Further research is necessary to elucidate the true effect of the depolarization and repolarization waveform and defibrillator patches.

Aged↗

Characterization of a strain of cerebral endothelial cells derived from goat brain which retain their differentiated traits after long-term passage.

A strain of cerebral endothelial cells was established from isolated cortical microvessels of caprine brain. These cells, which are referred to as EC1 cells, can be routinely subcultured to 32 passages without the loss of differentiated morphologic and immunologic traits. The ability to routinely subculture EC1 cells is an important asset, given that isolated cerebral endothelial cells in mammals generally lose their differentiated traits after only 2 to 3 passages. EC1 cells were shown to contain Factor VIII-related antigen, which is a specific marker for cells of endothelial origin. EC1 cells morphologically demonstrated a scarcity of pinocytotic vesicles on their apical surfaces, a lack of trans-cytoplasmic vesicles, and the ability to form in culture confluent monolayers with tight junctional complexes. Therefore, EC1 cells possess specific antigenic and ultrastructural features which classify them as being small vessel endothelial cells of the blood-brain barrier type. Cytogenetic evaluation of EC1 cells demonstrated a normal female goat 60,XX karyotype and confirmed the apparent non-transformed nature of EC1 cells due to the lack of chromosome abnormalities or rearrangements. Using scanning electron microscopy, EC1 cells were also shown to form confluent monolayers on mixed nitrocellulose filters, a feature that will enable the development of an in vitro system to study trans-endothelial transport. Given that EC1 cells are readily subcultured and grow well on nitrocellulose filters, and that they resemble cerebral endothelium in vivo, it seems evident that EC1 cells can be used as a versatile model for the study of blood-brain barrier function, regulation, and pathology.

Animals↗