We study exocytosis in the planar isolated cortex of the egg of the sea urchinLytechinus pictus. ... more We study exocytosis in the planar isolated cortex of the egg of the sea urchinLytechinus pictus. Solutins bathing the exocytotic apparatus need not contain appreciable amounts of ions: fusion follows addition of submicromolar calcium to solutions containing only nonelectrolyte. We examine the effects of altering the granule membrane permeability to small molecules with ionophores and digitonin. Introducing holes in the secretory granule membrane to the extent of allowing free passage of small molecules does not cause seretion in vitro. We add the amphipathic compound digitonin at 12 to 15 μM concentrations and demonstrate that the granule membrane can become permeable to lucifer yellow, yet that granules remain intact. Granules still undergo exocytosis after digitonin treatment at such concentrations upon subsequent addition of calcium. Higher concentrations of digitonin lead to granule content swelling and vesicle bursting. We conclude that cortical granule hydration during exocytosis is not mediated by small ionic channels.
Chronic hepatitis B (CHB) may lead to cirrhosis and hepatocellular carcinoma. Treatment with mono... more Chronic hepatitis B (CHB) may lead to cirrhosis and hepatocellular carcinoma. Treatment with monotherapy, using either a nucleoside or nucleotide analogues, has been recommended, though phenotypic and genotypic resistance is not uncommon while on treatment. Combination with a nucleoside and a nucleotide analogue can lead to a more rapid viral suppression, and prevention of resistance to treatment. Aim: To investigate the swiftness of combination treatment in the viral load decline and seroconversion using adefovir 10 mg and lamivudine 100 -300 mg daily. Methods: This is a retrospective chart review study of patients with chronic hepatitis B undergoing combination treatment. A total of 25 patients (15 men and 10 women) median age of 45 years old, were studied. Twenty patients were naïve, five patients underwent treatment in the past, zero developed resistance and four were non-adherent. Eighty percent of the patients were found to be e antigen negative. Liver biopsy was performed on 76% of patients, and 20% were identified with cirrhosis. At initiation of therapy, 10 of 25 patients had elevated AST (median 71) and 11 of 25 had elevated ALT (median 58). The median viral load at initiation was 23,100 IU/ml (viral load was measured by HBV QuantaSure, LabCorp). The viral load was checked between every 3 weeks to 3 months. No virologic breakthrough was noted for those patients who remained on treatment. Fifteen of eighteen patients had either precore or BCP mutations (13 e Antigen negative, 2 e Antigen positive). Genotyping was done for 74% of the patients. The distribution was: 41 % type A, 35% type B, 18 % type C, and 6 % type D. Results: By week 21, all 25 patients had achieved an undetectable viral load (<100 IU/mL) and continued undetectable if they stayed on medication. Four patients stopped treatment and experienced a rise in the viral load. The mean time on therapy was 82 weeks (range 34 to 198 weeks). No virologic breakthrough occurred in patients who continued treatment. For the e antigen population, complete e antigen seroconversion was achieved in 67% of the patients at a median time of 54 weeks. The liver enzymes were normalized in 24 of 25 patients. Two of the patients underwent orthotopic liver transplantation shortly after initiation of treatment, and though the viral load was detectable at the time of the procedure, it became undetectable shortly after. Conclusion: Effective and rapid viral suppression may be achieved by using the combination of a nucleotide agent with a nucleoside analogue. Combination therapy may avoid the development of resistance. Sustainability is something that has to be further evaluated.
Purpose Entecavir demonstrated superior virologic and biochemical benefits over lamivudine at 48 ... more Purpose Entecavir demonstrated superior virologic and biochemical benefits over lamivudine at 48 weeks in nucleoside-naïve Chinese patients with chronic hepatitis B (CHB). We evaluated the effect of continued entecavir and lamivudine treatment in patients who continued treatment in year 2 and the off-treatment durability of patients who achieved a protocol-defined consolidated response at week 48. Methods Chinese adults (n = 519) with CHB were randomized to a minimum of 52 weeks of treatment with entecavir 0.5 mg/day or lamivudine 100 mg/day. Patients with a consolidated response at week 48 (HBV DNA <0.7 MEq/ml for ≥24 weeks, ALT <1.25 times ULN, and, if HBeAg(+) at baseline, loss of HBeAg for at least 24 weeks) stopped treatment at week 52 and were followed off-treatment. Patients with a partial response at week 48 (HBV DNA <0.7 MEq/ml in the absence of other criteria for a consolidated response) could continue blinded treatment for up to 96 weeks. Patients were assessed for HBV DNA, ALT normalization, safety, and, if HBeAg(+) at baseline, for HBe seroconversion. Cumulative proportions of all treated patients who ever achieved these responses were also analyzed. Results Among patients treated during year 2 (entecavir: n = 193; lamivudine: n = 145), 74% of entecavir-treated and 41% of lamivudine-treated patients had HBV DNA <300 copies/ml by PCR at end of dosing and 96% of entecavir-treated and 82% of lamivudine-treated patients normalized ALT. Eleven percent of entecavir-treated versus 19% of lamivudine-treated patients underwent HBe seroconversion during year 2. Cumulative confirmed analysis for all treated patients through 96 weeks showed that 79% of entecavir-treated versus 46% of lamivudine-treated patients (p < 0.0001) achieved HBV DNA <300 copies/ml by PCR. Similar proportions of entecavir- and lamivudine-treated patients achieved confirmed ALT normalization and HBe seroconversion. Safety profile was comparable for both treatment groups. Conclusions Through 96 weeks of treatment, entecavir resulted in continued clinical benefit in nucleoside-naïve Chinese patients with CHB, with a safety profile comparable with lamivudine.
Purpose This randomized, double-blind, placebo-controlled study was undertaken to evaluate the ef... more Purpose This randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and safety of entecavir in Chinese patients with lamivudine-refractory chronic hepatitis B. Methods One hundred forty-five lamivudine-refractory patients with chronic hepatitis B were randomized to double-blind treatment with oral entecavir 1 mg (n = 116) or placebo (n = 29) daily for 12 weeks, followed by 36 weeks of open-label entecavir treatment. The primary efficacy endpoint was the mean change from baseline in serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR) assay at week 12. Results At week 12, the mean change from baseline in serum HBV DNA by PCR assay was –4.30 log10 copies/ml for patients on entecavir compared to –0.15 log10 copies/ml for patients on placebo (P < .0001). Among patients with baseline serum alanine aminotransferase (ALT) >1 × upper limit of normal (ULN), a higher proportion of entecavir than placebo patients (68% vs. 6%, respectively) achieved ALT normalization by week 12 (P < .0001). After 48 weeks of entecavir treatment, the mean change in HBV DNA by PCR assay was –5.08 log10 copies/ml, and 85% of patients with baseline ALT >1 × ULN had achieved ALT normalization. The safety profile of entecavir was similar to that of placebo during the first 12 weeks of blinded dosing. Entecavir was also well tolerated during 36 weeks of open-label treatment. Conclusions Lamivudine-refractory chronic hepatitis B patients treated with entecavir demonstrated marked HBV DNA reduction and normalization of ALT in most cases. Entecavir treatment for 48 weeks was well tolerated.
Background/Aims Chronic hepatitis B has a high prevalence (>8%) in China. We compared the safety ... more Background/Aims Chronic hepatitis B has a high prevalence (>8%) in China. We compared the safety and efficacy of entecavir with that of lamivudine for the treatment of patients with chronic hepatitis B in China. Methods A total of 519 nucleoside-naive Chinese patients with chronic hepatitis B were randomized (1:1) and treated with entecavir 0.5 mg/d or lamivudine 100 mg/d. The primary endpoint was serum HBV DNA <0.7 MEq/ml by bDNA assay and alanine aminotransferase <1.25 × upper limit of normal (ULN) at week 48. Patients with missing week 48 measurements were considered non-responders. Results About 90% (231/258) of entecavir-treated versus 67% (174/261) of lamivudine-treated patients achieved the primary endpoint (P < 0.0001). The mean reduction from baseline in HBV DNA was greater with entecavir than lamivudine (5.90 vs. 4.33 log10 copies/ml, P < 0.0001). Greater proportions of entecavir-treated patients achieved undetectable HBV DNA (<300 copies/ml) by polymerase chain reaction assay (76% vs. 43%, P < 0.0001) and alanine aminotransferase normalization (≤1 × ULN, 90% vs. 78%, P = 0.0003). Entecavir and lamivudine achieved comparable rates of HBeAg seroconversion (15% and 18%, respectively). Safety was comparable between the two treatments. Conclusions For nucleoside-naïve Chinese patients with chronic hepatitis B, entecavir achieves superior virological and biochemical benefit over lamivudine, with a comparable safety profile.
Therapeutic ultrasound guided by magnetic resonance imaging (MRI) is a noninvasive treatment that... more Therapeutic ultrasound guided by magnetic resonance imaging (MRI) is a noninvasive treatment that potentially reduces mortality, lowers medical costs, and widens accessibility of treatments for patients. Recent developments in the design and fabrication of capacitive micromachined ultrasonic transducers (CMUTs) have made them competitive with piezoelectric transducers for use in therapeutic ultrasound applications. In this paper, we present the first designs and prototypes of an 8element, concentric-ring, CMUT array to treat upper abdominal cancers. This array was simulated and designed to focus 30-50 mm into tissue and ablate a 2-3 cm diameter tumor within 1 hour. Assuming a surface acoustic output pressure of 1 MPa peak to peak (8.5 W/cm2) at 2.5 MHz, we simulated an array that produced a focal intensity of 680 W/cm 2 when focusing to 35 mm. CMUT cells were then designed to meet these frequency and surface acoustic intensity specifications. These cell designs were fabricated as 2.5 mm by 2.5 mm test transducers and used to verify our models. The test transducers were shown to operate at 2.5 MHz with an output pressure of 1.4 MPa peak to peak (16.3 W/cm 2 ). With this CMUT cell design, we fabricated a full 8-element array. Due to yield issues, we only developed electronics to focus the four center elements of the array. The beam profile of the measured array deviated from the simulated because of crosstalk effects; the beamwidth matched within 10% and sidelobes increased by 2 times, which caused the measured gain to be 16.6 compared to 27.4.
We study exocytosis in the planar isolated cortex of the egg of the sea urchinLytechinus pictus. ... more We study exocytosis in the planar isolated cortex of the egg of the sea urchinLytechinus pictus. Solutins bathing the exocytotic apparatus need not contain appreciable amounts of ions: fusion follows addition of submicromolar calcium to solutions containing only nonelectrolyte. We examine the effects of altering the granule membrane permeability to small molecules with ionophores and digitonin. Introducing holes in the secretory granule membrane to the extent of allowing free passage of small molecules does not cause seretion in vitro. We add the amphipathic compound digitonin at 12 to 15 μM concentrations and demonstrate that the granule membrane can become permeable to lucifer yellow, yet that granules remain intact. Granules still undergo exocytosis after digitonin treatment at such concentrations upon subsequent addition of calcium. Higher concentrations of digitonin lead to granule content swelling and vesicle bursting. We conclude that cortical granule hydration during exocytosis is not mediated by small ionic channels.
Chronic hepatitis B (CHB) may lead to cirrhosis and hepatocellular carcinoma. Treatment with mono... more Chronic hepatitis B (CHB) may lead to cirrhosis and hepatocellular carcinoma. Treatment with monotherapy, using either a nucleoside or nucleotide analogues, has been recommended, though phenotypic and genotypic resistance is not uncommon while on treatment. Combination with a nucleoside and a nucleotide analogue can lead to a more rapid viral suppression, and prevention of resistance to treatment. Aim: To investigate the swiftness of combination treatment in the viral load decline and seroconversion using adefovir 10 mg and lamivudine 100 -300 mg daily. Methods: This is a retrospective chart review study of patients with chronic hepatitis B undergoing combination treatment. A total of 25 patients (15 men and 10 women) median age of 45 years old, were studied. Twenty patients were naïve, five patients underwent treatment in the past, zero developed resistance and four were non-adherent. Eighty percent of the patients were found to be e antigen negative. Liver biopsy was performed on 76% of patients, and 20% were identified with cirrhosis. At initiation of therapy, 10 of 25 patients had elevated AST (median 71) and 11 of 25 had elevated ALT (median 58). The median viral load at initiation was 23,100 IU/ml (viral load was measured by HBV QuantaSure, LabCorp). The viral load was checked between every 3 weeks to 3 months. No virologic breakthrough was noted for those patients who remained on treatment. Fifteen of eighteen patients had either precore or BCP mutations (13 e Antigen negative, 2 e Antigen positive). Genotyping was done for 74% of the patients. The distribution was: 41 % type A, 35% type B, 18 % type C, and 6 % type D. Results: By week 21, all 25 patients had achieved an undetectable viral load (<100 IU/mL) and continued undetectable if they stayed on medication. Four patients stopped treatment and experienced a rise in the viral load. The mean time on therapy was 82 weeks (range 34 to 198 weeks). No virologic breakthrough occurred in patients who continued treatment. For the e antigen population, complete e antigen seroconversion was achieved in 67% of the patients at a median time of 54 weeks. The liver enzymes were normalized in 24 of 25 patients. Two of the patients underwent orthotopic liver transplantation shortly after initiation of treatment, and though the viral load was detectable at the time of the procedure, it became undetectable shortly after. Conclusion: Effective and rapid viral suppression may be achieved by using the combination of a nucleotide agent with a nucleoside analogue. Combination therapy may avoid the development of resistance. Sustainability is something that has to be further evaluated.
Purpose Entecavir demonstrated superior virologic and biochemical benefits over lamivudine at 48 ... more Purpose Entecavir demonstrated superior virologic and biochemical benefits over lamivudine at 48 weeks in nucleoside-naïve Chinese patients with chronic hepatitis B (CHB). We evaluated the effect of continued entecavir and lamivudine treatment in patients who continued treatment in year 2 and the off-treatment durability of patients who achieved a protocol-defined consolidated response at week 48. Methods Chinese adults (n = 519) with CHB were randomized to a minimum of 52 weeks of treatment with entecavir 0.5 mg/day or lamivudine 100 mg/day. Patients with a consolidated response at week 48 (HBV DNA <0.7 MEq/ml for ≥24 weeks, ALT <1.25 times ULN, and, if HBeAg(+) at baseline, loss of HBeAg for at least 24 weeks) stopped treatment at week 52 and were followed off-treatment. Patients with a partial response at week 48 (HBV DNA <0.7 MEq/ml in the absence of other criteria for a consolidated response) could continue blinded treatment for up to 96 weeks. Patients were assessed for HBV DNA, ALT normalization, safety, and, if HBeAg(+) at baseline, for HBe seroconversion. Cumulative proportions of all treated patients who ever achieved these responses were also analyzed. Results Among patients treated during year 2 (entecavir: n = 193; lamivudine: n = 145), 74% of entecavir-treated and 41% of lamivudine-treated patients had HBV DNA <300 copies/ml by PCR at end of dosing and 96% of entecavir-treated and 82% of lamivudine-treated patients normalized ALT. Eleven percent of entecavir-treated versus 19% of lamivudine-treated patients underwent HBe seroconversion during year 2. Cumulative confirmed analysis for all treated patients through 96 weeks showed that 79% of entecavir-treated versus 46% of lamivudine-treated patients (p < 0.0001) achieved HBV DNA <300 copies/ml by PCR. Similar proportions of entecavir- and lamivudine-treated patients achieved confirmed ALT normalization and HBe seroconversion. Safety profile was comparable for both treatment groups. Conclusions Through 96 weeks of treatment, entecavir resulted in continued clinical benefit in nucleoside-naïve Chinese patients with CHB, with a safety profile comparable with lamivudine.
Purpose This randomized, double-blind, placebo-controlled study was undertaken to evaluate the ef... more Purpose This randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and safety of entecavir in Chinese patients with lamivudine-refractory chronic hepatitis B. Methods One hundred forty-five lamivudine-refractory patients with chronic hepatitis B were randomized to double-blind treatment with oral entecavir 1 mg (n = 116) or placebo (n = 29) daily for 12 weeks, followed by 36 weeks of open-label entecavir treatment. The primary efficacy endpoint was the mean change from baseline in serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR) assay at week 12. Results At week 12, the mean change from baseline in serum HBV DNA by PCR assay was –4.30 log10 copies/ml for patients on entecavir compared to –0.15 log10 copies/ml for patients on placebo (P < .0001). Among patients with baseline serum alanine aminotransferase (ALT) >1 × upper limit of normal (ULN), a higher proportion of entecavir than placebo patients (68% vs. 6%, respectively) achieved ALT normalization by week 12 (P < .0001). After 48 weeks of entecavir treatment, the mean change in HBV DNA by PCR assay was –5.08 log10 copies/ml, and 85% of patients with baseline ALT >1 × ULN had achieved ALT normalization. The safety profile of entecavir was similar to that of placebo during the first 12 weeks of blinded dosing. Entecavir was also well tolerated during 36 weeks of open-label treatment. Conclusions Lamivudine-refractory chronic hepatitis B patients treated with entecavir demonstrated marked HBV DNA reduction and normalization of ALT in most cases. Entecavir treatment for 48 weeks was well tolerated.
Background/Aims Chronic hepatitis B has a high prevalence (>8%) in China. We compared the safety ... more Background/Aims Chronic hepatitis B has a high prevalence (>8%) in China. We compared the safety and efficacy of entecavir with that of lamivudine for the treatment of patients with chronic hepatitis B in China. Methods A total of 519 nucleoside-naive Chinese patients with chronic hepatitis B were randomized (1:1) and treated with entecavir 0.5 mg/d or lamivudine 100 mg/d. The primary endpoint was serum HBV DNA <0.7 MEq/ml by bDNA assay and alanine aminotransferase <1.25 × upper limit of normal (ULN) at week 48. Patients with missing week 48 measurements were considered non-responders. Results About 90% (231/258) of entecavir-treated versus 67% (174/261) of lamivudine-treated patients achieved the primary endpoint (P < 0.0001). The mean reduction from baseline in HBV DNA was greater with entecavir than lamivudine (5.90 vs. 4.33 log10 copies/ml, P < 0.0001). Greater proportions of entecavir-treated patients achieved undetectable HBV DNA (<300 copies/ml) by polymerase chain reaction assay (76% vs. 43%, P < 0.0001) and alanine aminotransferase normalization (≤1 × ULN, 90% vs. 78%, P = 0.0003). Entecavir and lamivudine achieved comparable rates of HBeAg seroconversion (15% and 18%, respectively). Safety was comparable between the two treatments. Conclusions For nucleoside-naïve Chinese patients with chronic hepatitis B, entecavir achieves superior virological and biochemical benefit over lamivudine, with a comparable safety profile.
Therapeutic ultrasound guided by magnetic resonance imaging (MRI) is a noninvasive treatment that... more Therapeutic ultrasound guided by magnetic resonance imaging (MRI) is a noninvasive treatment that potentially reduces mortality, lowers medical costs, and widens accessibility of treatments for patients. Recent developments in the design and fabrication of capacitive micromachined ultrasonic transducers (CMUTs) have made them competitive with piezoelectric transducers for use in therapeutic ultrasound applications. In this paper, we present the first designs and prototypes of an 8element, concentric-ring, CMUT array to treat upper abdominal cancers. This array was simulated and designed to focus 30-50 mm into tissue and ablate a 2-3 cm diameter tumor within 1 hour. Assuming a surface acoustic output pressure of 1 MPa peak to peak (8.5 W/cm2) at 2.5 MHz, we simulated an array that produced a focal intensity of 680 W/cm 2 when focusing to 35 mm. CMUT cells were then designed to meet these frequency and surface acoustic intensity specifications. These cell designs were fabricated as 2.5 mm by 2.5 mm test transducers and used to verify our models. The test transducers were shown to operate at 2.5 MHz with an output pressure of 1.4 MPa peak to peak (16.3 W/cm 2 ). With this CMUT cell design, we fabricated a full 8-element array. Due to yield issues, we only developed electronics to focus the four center elements of the array. The beam profile of the measured array deviated from the simulated because of crosstalk effects; the beamwidth matched within 10% and sidelobes increased by 2 times, which caused the measured gain to be 16.6 compared to 27.4.
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Papers by Jessica Liu