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C Hwang

Publications and source records attributed to C Hwang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prospects and limitations of recombinant poxviruses for prostate cancer immunotherapy.

Prostate cancer is a disease that may be amenable to immunotherapy approaches, as evidenced by the ability to induce human cytotoxic immune responses against prostate cancer cells. Recent interest in recombinant poxvirus vaccines coupled with the need for new prostate cancer therapies has led to the development of several recombinant poxvirus agents designed for prostate cancer treatment. Whether these agents will be effective in treating prostate cancer is under investigation in several ongoing and upcoming clinical trials. In the meantime, data from preclinical tumor models have provided information that may aid in improving recombinant poxviruses for clinical use. While animal studies have shown the ability of recombinant poxvirus vaccination to induce an immune response that protects against lethal tumor, these antitumor effects are variable and depend on a number of factors. Co-expression of immunomodulating gene products, such as cytokines and costimulatory molecules, have been shown to influence antitumor immunity; in fact, cytokine delivery alone can be enough to protect against tumor-related death. Patterns and levels of recombinant antigen expression also affect the immune response to that antigen, as seen by studies of various poxvirus promoters and cell compartment-targeting sequences. In addition, vaccine strategies targeting self-antigens have shown that immunological tolerance can negatively impact the induction of antitumor and antigen-specific immunity. Although vaccinia virus has been most intensely studied thus far, other poxviruses, including fowlpox and canarypox, are also promising vaccine candidates. These alternative vectors may circumvent some of the disadvantages associated with vaccinia virus, such as pre-existing vaccinia immunity. A deeper understanding of these factors and others that impact the development of antitumor immunity will be necessary to guide the development of recombinant poxviruses for prostate cancer therapy.

Adenocarcinoma↗
PubMed1998

Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry.

OBJECTIVES: We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF. BACKGROUND: The role of increased fibrosis in reentry formation during human VF is unclear. METHODS: Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF. A plaque electrode array with 477 bipolar electrodes (1.6-mm resolution) was used for epicardial mapping. In heart no. 5, we also used 440 transmural bipolar recordings. Each mapped area was analyzed histologically. RESULTS: Fifteen runs of VF (8 s/run) recorded from the epicardium were analyzed, and 55 episodes of reentry were observed. The life span of reentry was short (one to four cycles), and the mean cycle length was 172 +/- 24 ms. In heart no. 5, transmural scroll waves were demonstrated. The most common mode of initiation of reentry was epicardial breakthrough, followed by a line of conduction block parallel to the epicardial fiber orientation (34 [62%] of 55 episodes). In the areas with lines of block, histologic examination showed significant fibrosis separating the epicardial muscle fibers and bundles along the longitudinal axis of fiber orientation. The mean percent fibrous tissue in these areas (n = 20) was significantly higher than that in the areas without block (n = 28) (24 +/- 7.5% vs. 10 +/- 3.8%, p < 0.0001). CONCLUSIONS: In human hearts with DCM, epicardial reentrant wave fronts and transmural scroll waves were present during VF. Increased fibrosis provides a site for conduction block, leading to the continuous generation of reentry.

Adolescent↗
PubMed1998

US double-blind, controlled trials of omeprazole and amoxycillin for treatment of Helicobacter pylori.

BACKGROUND: Widely variable Helicobacter pylori eradication rates have been reported with omeprazole/amoxycillin dual therapy. We present the first US double-blind, controlled trials of this dual therapy. METHODS: Three separate studies were performed: Studies 1 and 2 included patients with an active duodenal ulcer and Study 3 included patients with a documented history of duodenal ulcer. H. pylori eradication regimens in all studies were omeprazole plus amoxycillin vs. omeprazole vs. amoxycillin for 2 weeks. Doses in Study 1 were omeprazole 40 mg b.d. and amoxycillin 500 mg t.d.s., and in Studies 2 and 3 they were omeprazole 20 mg b.d. and amoxycillin 1 g t.d.s. Endoscopic biopsy tests were used for H. pylori diagnosis, and testing for H. pylori eradication was done at least 4 weeks after the completion of therapy. Amoxycillin sensitivities were performed in Study 2. RESULTS: Intention-to-treat (ITT) and per protocol (PP) analyses showed that eradication rates with omeprazole/amoxycillin [ITT: 39%, 40%, 46% (n = 72, 62, 48); PP: 50%, 46%, 54% (n = 54, 52, 37)] were significantly greater than monotherapy with either omeprazole (ITT: 0-4%); PP: 0-5%) or amoxycillin (ITT: 2-5%; PP: 0-11%). No patients taking the dual therapy discontinued therapy due to adverse events. Amoxycillin resistance was not seen at baseline (n = 76) or after amoxycillin therapy (n = 56). CONCLUSIONS: Omeprazole/amoxycillin dual therapy is well tolerated but the eradication rate which can be expected in the USA is at best about 50%.

Administration, Oral↗
PubMed1998

Current concepts of ventricular defibrillation.

The aim of this article is to review the current concepts of ventricular defibrillation. We studied the interaction between strong electrical stimulus and cardiac responses in both animal models and in humans. We found that a premature stimulus (S2) of appropriate strength results in figure-eight reentry in vitro by inducing propagated graded responses. The same stimulation protocol induces figure-eight reentry and ventricular fibrillation (VF) in vivo. When the S2 strength and the magnitude of graded responses increase beyond a critical level, the increase in refractoriness at the site of the stimulus becomes so long that the unidirectional block becomes bidirectional block, preventing the formation of reentry (upper limit of vulnerability [ULV]). In other studies, we found that the effects of an electrical stimulation on reentry is in part determined by the timing of the stimulus. A protective zone is present after the induction of VF and after an unsuccessful defibrillation shock during which an electrical stimulus can terminate reentry and protect the heart from VF. These results indicate that the effects of a defibrillation shock is dependent on both the strength and the timing of the shock. Timing is not important in areas where the shock field strength is > or = ULV because the shock terminates all reentry but cannot reinitiate new ones. However, in areas where shock field strength is < ULV, the effects of the shock are determined by the timing of the shock relative to local VF activations. This ULV hypothesis of defibrillation explains the probabilistic nature of ventricular defibrillation. It also indicates that, to achieve a high probability of successful defibrillation, a shock must result in a shock field strength of > or = ULV throughout the ventricles.

Animals↗
PubMed1998

The Shc 66 and 46 kD isoforms are differentially downregulated at parturition in the fetal mouse lung.

Many of the signaling pathways regulating fetal lung mesenchymal cell proliferation are mediated by the Shc intracellular signaling proteins. Shc is expressed as three isoforms: 52 kD and 46 kD proteins (Shc 52 and Shc 46, respectively) translated from the same mRNA, and a 66 kD form (Shc 66) translated from a separate mRNA. Shc 52 is an activator of Ras and mitogen-activated protein kinase, whereas Shc 66 antagonizes Ras activation. The function of Shc 46 is unclear. We hypothesized that the Shc isoforms are differentially regulated during fetal mouse lung morphogenesis. Relative Shc 66 and Shc 46 protein expression are high until parturition (term = 18.5 d), when a dramatic decrease begins; by postconceptual d 20, relative Shc 66 and Shc 46 expression have fallen by 75 and 69%, respectively. A similar pattern of decreasing Shc 66 mRNA expression in the peripartum period was detected by reverse transcription and competitive polymerase chain reaction during the same period. By isoform-specific immunohistochemistry, Shc 66 is widely distributed in the embryonic lung but becomes restricted to the bronchial smooth muscle and overlying epithelia, periarterial smooth muscle, and the interlobar pleura late in gestation. After parturition, Shc 66 is virtually absent from the lung. All three Shc isoforms are phosphorylated by epidermal growth factor stimulation in fetal lung mesenchymal cells, indicating that Shc 66 is functional in these cells. These data indicate that Shc isoforms are differentially regulated during lung development.

3T3 Cells↗
PubMed1997

Induction of meandering functional reentrant wave front in isolated human atrial tissues.

BACKGROUND: The purpose of this study was to test the hypothesis that a single meandering functional reentrant wave front can result in rapid and irregular electrogram activity in human atrial tissues. METHODS AND RESULTS: The study used the explanted hearts of five human cardiac transplant recipients. Three right and two left atrial tissue samples, 3.4+/-0.3 mm thick, were excised and trimmed to 3.5x3.0 cm. The isolated atrium was placed endocardial surface down in a chamber with a 477 bipolar recording electrode array built into the bottom of the tissue bath. The interelectrode distance was 1.6 mm. The tissue was constantly superfused with 36.5 degrees C oxygenated Tyrode's solution at a rate of 10 mL/min. After eight baseline stimuli (S1) delivered at 400- or 600-ms cycle length from the edge of the tissue, a single premature stimulus (S2) was given at the center of the tissue to induce reentry. A total of nine episodes of reentry were induced with S1-S2 coupling intervals of 232+/-29 ms (range, 190 to 290 ms) and an S2 strength of 10+/-3 mA (range, 5 to 15 mA). In all samples, a single meandering reentrant wave front was induced, causing irregular and rapid bipolar electrogram activity. These wave fronts had a mean cycle length of 229+/-45 ms (160 to 290 ms) and persisted for 1.1+/-0.3 seconds (0.6 seconds to 2.5 seconds), or 5.2+/-1.4 (3 to 9) cycles, before spontaneous termination. CONCLUSIONS: A single meandering functional reentrant wave front can be induced in human atrial tissues and produce rapid and irregular electrical activity.

Adult↗
PubMed1997

Programming of implantable cardioverter-defibrillators on the basis of the upper limit of vulnerability.

BACKGROUND: A patient-specific measure of defibrillation efficacy that requires a minimum number of ventricular fibrillation (VF) episodes would be valuable for programming implantable cardioverter-defibrillators (ICDs). The upper limit of vulnerability (ULV) is the weakest shock strength at or above which VF is not induced when a stimulus is delivered during the vulnerable phase of the cardiac cycle. It correlates with the defibrillation threshold (DFT) and can be determined with a single episode of VF. The objective of this study was to test the hypothesis that ICDs programmed on the basis of the ULV convert spontaneous ICD-detected VF reliably. METHODS AND RESULTS: We studied 100 consecutive patients at ICD implantation and during follow-up of 20 +/- 7 months. At implantation, the ULV and DFT were determined, and the ICD system was tested at a shock strength equal to the ULV + 3 J. During follow-up, the strength of the first shock was programmed to the ULV + 5 J for arrhythmias detected in the VF zone (cycle length < 292 +/- 17 ms). We reviewed stored detection intervals and electrograms from spontaneous episodes of ICD-detected VF to determine the success rate for appropriate first shocks. The programmed first-shock strength was 17.5 +/- 5.2 J. During follow-up, there were 120 appropriate first shocks in 37 patients. The arrhythmia was rapid monomorphic ventricular tachycardia (VT) in 70% of episodes (31 patients), VF in 11% (13 patients), polymorphic VT in 1%, and unclassified in 17% (15 patients). The first shock was successful in 119 of 120 episodes (99%; 95% CI, 93% to 100%). One unclassified episode required two shocks. No patient had syncope associated with an ICD shock or arrhythmic death. CONCLUSIONS: ICD shocks can be programmed on the basis of the ULV, a measurement made in regular rhythm, without a direct measure of defibrillation efficacy.

Aged↗
PubMed1997

Quasiperiodicity and chaos in cardiac fibrillation.

In cardiac fibrillation, disorganized waves of electrical activity meander through the heart, and coherent contractile function is lost. We studied fibrillation in three stationary forms: in human chronic atrial fibrillation, in a stabilized form of canine ventricular fibrillation, and in fibrillation-like activity in thin sheets of canine and human ventricular tissue in vitro. We also created a computer model of fibrillation. In all four studies, evidence indicated that fibrillation arose through a quasiperiodic stage of period and amplitude modulation, thus exemplifying the "quasiperiodic transition to chaos" first suggested by Ruelle and Takens. This suggests that fibrillation is a form of spatio-temporal chaos, a finding that implies new therapeutic approaches.

Action Potentials↗
PubMed1997

Regulation of thyroid hormones in the secretion of insulin and gastric inhibitory polypeptide in male rats.

The effect of thyroid hormones on glucose-induced secretion of gastric inhibitory polypeptide (GIP) and insulin was studied. Male rats were thyroidectomized (Tx) or sham Tx. Sham Tx rats were injected with either propylthiouracil ([PTU] 20 mg/kg intraperitoneally) or saline for 2 weeks. In addition, thyroid-intact rats were injected intravenously with triiodothyronine ([T3]5 microg/kg) or saline 10 minutes before an oral glucose load (3.2 g/kg). Blood samples were collected from each animal via a jugular catheter at 0, 10, 20, 30,45, 60, and 90 minutes following glucose ingestion. Plasma levels of GIP and insulin were measured by specific radioimmunoassays (RIAs). Thyroidectomy-induced hypothyroidism increased the basal level of plasma GIP, but decreased that of insulin. Insulin levels at 10, 20, and 30 minutes following oral glucose were lower in hypothyroid rats than in euthyroid rats. Conversely, GIP levels at 60 and 90 minutes following glucose ingestion in PTU-induced hypothyroid rats were higher than those in euthyroid rats. Furthermore, glucose-stimulated insulin secretion was unaltered by pretreatment with T3, whereas the glucose-induced increase in plasma GIP was completely abolished by preinjection of T3 in thyroid-intact rats. These results suggest that thyroid functions are involved in the regulation of insulin and GIP secretion in rats.

Animals↗
PubMed1997

Atypical atrioventricular node reciprocating tachycardia masquerading as tachycardia using a left-sided accessory pathway.

OBJECTIVES: The study was performed to document that atrioventricular node reciprocating tachycardia (AVNRT) can be associated with eccentric retrograde left-sided activation, masquerading as tachycardia using a left accessory pathway. BACKGROUND: The eccentric retrograde left-sided activation during tachycardia is thought to be diagnostic of the presence of a left free wall accessory pathway. However, it is not known whether AVNRT can occur with eccentric retrograde left-sided activation. METHODS: We studied 356 patients with AVNRT who underwent catheter ablation. Retrograde atrial activation during tachycardia and ventricular pacing were determined by intracardiac recordings, including the use of a decapolar coronary sinus catheter. RESULTS: The retrograde atrial activation was eccentric in 20 patients (6%). Eight of these patients had the earliest retrograde atrial activation recorded in the lateral coronary sinus leads, and 12 had the earliest retrograde atrial activation recorded in the posterior coronary sinus leads, with the most proximal coronary sinus electrode pair straddling the coronary sinus orifice. These tachycardias were either the fast-slow or the slow-slow form of AVNRT. The slow-fast form of AVNRT was also inducible in 17 of the 20 patients. Successful ablation of the slow pathway in the right atrial septum near the coronary sinus ostium prevented the induction and clinical recurrence of reciprocating tachycardia in all patients. CONCLUSIONS: Atypical AVNRT with eccentric retrograde left-sided activation was demonstrated in 6% of all patients with AVNRT masquerading as tachycardia using a left-sided accessory pathway. Ablation of the slow pathway at the posterior aspects of the right atrial septum resulted in a cure in these patients.

Adult↗
PubMed1997

Upper limit of vulnerability predicts chronic defibrillation threshold for transvenous implantable defibrillators.

INTRODUCTION: The upper limit of vulnerability (ULV) is the shock strength at or above which ventricular fibrillation cannot be induced when delivered in the vulnerable period. It correlates acutely with the acute defibrillation threshold (DFT) and can be determined with a single episode of fibrillation. The goal of this prospective study was to determine the relationship between the ULV and the chronic DFT. METHODS AND RESULTS: We studied 40 patients at, and 3 months after, implantation of transvenous cardioverter defibrillators. The ULV was defined as the weakest biphasic shock that failed to induce fibrillation when delivered 0, 20, and 40 msec before the peak of the T wave. patients were classified as clinically stable or unstable based on prospectively defined criteria. There were no significant differences between the group means for the acute and chronic determinations of ULV (13.5 +/- 5.3 J vs 12.4 +/- 6.8 J, P = 0.25) and DFT (10.1 +/- 5.0 J vs 9.9 +/- 5.7 J, P = 0.74). Five patients (15%) were classified as unstable. The strength of the correlation between acute ULV and acute DFT (r = 0.74, P < 0.001) was similar to that between the chronic ULV and chronic DFT (r = 0.82, P < 0.001). There was a correlation between the change in ULV from acute to chronic and the corresponding change in DFT (r = 0.67, P < 0.001). The chronic DFT was less than the acute ULV +3 J in all 35 stable patients, but it was greater in 2 of 5 unstable patients (P = 0.04). CONCLUSIONS: The strength of the correlation between the chronic ULV and the chronic DFT is comparable to that between the acute ULV and the acute DFT. Temporal changes in the ULV predict temporal changes in the DFT. In clinically stable patients, a defibrillation safety margin of 3 J above the acute ULV proved an adequate chronic safety margin.

Aged↗
PubMed1997

TGF-beta isoforms differentially attenuate EGF mitogenicity and receptor activity in fetal lung mesenchymal cells.

To evaluate signaling interactions, combinations of epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) isoforms were applied to primary fetal mouse lung mesenchymal cells isolated at 16 days of gestation. The three isoforms of TGF-beta had similar mitogenic potentials, as assessed by thymidine incorporation (half-maximal effective concentration approximately 2 ng/ml). However, combined exposure to EGF and TGF-beta yielded an isoform-dependent attenuation of EGF-induced mitogenesis. Combinations of 20 ng/ml EGF and 2 ng TGF-beta 1, TGF-beta 2, or TGF-beta 3 resulted in thymidine incorporation values 0.76, 0.74, and 0.86 times that of EGF alone, respectively; attenuation of EGF mitogenicity, interactions between EGF and TGF-beta isoforms, and differences between isoforms were all statistically significant by analysis of variance. Treatment with TGF-beta isoforms significantly reduced EGF-induced receptor angiotensin II substrate phosphorylation. TGF-beta isoform-specific signaling also significantly attenuated EGF-induced phosphorylation of the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 2. These results suggest that isoform-specific TGF-beta signaling modulates the EGF signal transduction pathway upstream of MAP kinase.

Animals↗
PubMed1996

Diffuse Extreme-Ultraviolet Emission from the Coma Cluster: Evidence for Rapidly Cooling Gases at Submegakelvin Temperatures

The central region of the Coma cluster of galaxies was observed in the energy band from 0.065 to 0.245 kiloelectron volts by the Deep Survey telescope aboard the Extreme Ultraviolet Explorer. A diffuse emission halo of angular diameter approximately 30 arc minutes was detected. The extreme-ultraviolet (EUV) emission level exceeds that expected from the x-ray temperature gas in Coma. This halo suggests the presence of two more phases in the emitting gas, one at a temperature of approximately 2 x 10(6) kelvin and the other at approximately 8 x 10(5) kelvin. The latter phase cools rapidly and, in steady state, would have produced cold matter with a mass of approximately 10(14) solar masses within the EUV halo. Although a similar EUV enhancement was discovered in the Virgo cluster, this detection in Coma applies to a noncooling flow system.

Journal Article↗
PubMed1996

Co-ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression.

During infection of their hosts, salmonellae enter intestinal epithelial cells. It has been proposed that when Salmonella typhimurium is present in the intestinal lumen, several environmental and regulatory conditions modulate the expression of invasion factors required for bacterial entry into host cells. We report here that the expression of six different S. typhimurium invasion genes encoded on SPI1 (Salmonella pathogenicity island 1) is co-ordinately regulated by oxygen, osmolarity, pH, PhoPQ, and HilA. HilA is a transcriptional activator of the OmpR/ToxR family that is also encoded on SPI1. We have found that HilA plays a central role in the co-ordinated regulation of invasion genes by environmental and regulatory conditions. HilA can activate the expression of two invasion gene-lacZY fusions on reporter plasmids in Escherichia coll, suggesting that HilA acts directly at invasion-gene promoters in S. typhimurium. We have found that the regulation of invasion genes by oxygen, osmolarity, pH, and PhoPQ is indirect and is mediated by regulation of hilA expression by these environmental and regulatory factors. We hypothesize that the complex and co-ordinate regulation of Invasion genes by HilA is an important feature of salmonella pathogenesis and allows salmonellae to enter intestinal epithelial cells.

Bacterial Proteins↗
PubMed1996

Short biphasic pulses from 90 microfarad capacitors lower defibrillation threshold.

For defibrillation between right ventricular and retropectoral patch electrodes using truncated exponential pulses, the stored energy defibrillation threshold (DFT) is lower for short pulses from small 60-microF capacitors than for conventional pulses from 120-microF capacitors, but 60-microF pulses frequently require higher voltages than are currently used. The goal of this study was to determine if DFT could be reduced by intermediate size 90-microF capacitors. This study compared biphasic waveform DFTs for 120 microF-65% tilt pulses, 90 microF-65% tilt pulses, and 90 microF-50% tilt pulses in 20 patients at defibrillator implantation. The 90 microF-50% tilt pulses were selected because their duration is half that of 120 microF-65% tilt pulses. The stored energy DFT for 90 microF-50% tilt pulses (9.1 +/- 4.3 J) was less than both the DFT for 120 microF-65% tilt pulses (12.0 +/- 5.5 J, P < 0.005) and the DFT for 90 microF-65% tilt pulses (11.6 +/- 5.8 J, P < 0.005). There was no significant difference between the latter two values. The voltage DFTs for 90 microF-50% pulses (436 +/- 113 V) and 120 microF-65% tilt pulses (436 +/- 104 V) were not statistically different; the voltage DFT for 90 microF-65% tilt pulses was higher than for either of the other two pulses (490 +/- 131, P < 0.005). The DFT was 20 J or greater in three patients for both 120 microF-65% tilt pulses and 90 microF-65% tilt pulses, but it was 16 J or less in all patients for 90 microF-50% tilt pulses. When pathways were dichotomized by the median resistance of 71 omega, 90 microF-50% tilt pulses significantly reduced DFTs compared to 120 microF-65% tilt pulses for higher resistance pathways (9.2 +/- 4.0 J vs 13.0 +/- 6.2 J, P = 0.002), but not lower resistance pathways (9.0 +/- 4.8 J vs 10.9 +/- 4.6 J, P = NS). For the electrode configuration tested, biphasic 90 microF-50% tilt pulses reduce stored energy DFT in comparison with 120 microF-65% tilt pulses without increasing voltage DFT. However, 90 microF-65% tilt pulses provide no benefit.

Defibrillators, Implantable↗
PubMed1996

Recurrent appearance of protective zones after an unsuccessful defibrillation shock.

This study was designed to test the hypothesis that protective zones appear recurrently at the initiation of ventricular fibrillation (VF) and that when shocks are delivered during protective zones, there can be a decrease in the defibrillation energy requirement. A total of 12 open-chest dogs were studied. Six dogs were included in protocol 1. After eight baseline pacing stimuli (S1) with cycle lengths of 300 ms, a strong premature stimulus (S2) (73 +/- 10 mA) was given to induce VF. In subsequent episodes, a second strong premature stimulus (S3) was given at progressively longer S2-S3 intervals in 20-ms increments. In protocol 2, we delivered unsuccessful defibrillation shocks via a transvenous defibrillation electrode placed in the right ventricular apex of six dogs. A second shock was then delivered to patch electrodes on the right ventricular outflow tract and the posterior wall of the left ventricle. The results of protocol 1 showed that the S3 terminated reentry and prevented VF only when it occurred at specific time intervals after the S2 (the protective zones). These protective zones appear recurrently up to 375 ms after the onset of VF. The results of protocol 2 showed that the total energy required for successful defibrillation was dependent on the interval between the first and second shocks. Intervals favoring effective defibrillation (protective zones) appeared recurrently for up to 280 ms after the first shock. When the second shock was delivered during a protective zone, the defibrillation energy requirement was decreased by up to 23% (from 13.1 +/- 2.0 to 10.1 +/- 1.8 J, P < 0.003). However, when the shock was delivered outside the protective zone, a significant increase in the defibrillation energy requirement was observed. We conclude that protective zones appear recurrently at the onset of VF and after unsuccessful defibrillation shocks.

Animals↗