Jae Hee park - Academia.edu (original) (raw)

Papers by Jae Hee park

Synthesis of Poly(Sorbitan Methacrylate) Hydrogel by Free-Radical Polymerization

Applied Biochemistry and Biotecnology, 2007

Hydrogels are materials with the ability to swell in water through the retention of significant f... more Hydrogels are materials with the ability to swell in water through the retention of significant fractions of water within their structures. Owing to their relatively high degree of biocompatibility, hydrogels have been utilized in a host of biomedical applications. In an attempt to determine the optimum conditions for hydrogel synthesis by the free-radical polymerization of sorbitan methacrylate (SMA), the hydrogel used in this study was well polymerized under the following conditions: 50% (w/v) SMA as monomer, 1% (w/w) alpha, alpha'-azo-bis(isobutyro-nitrile) as thermal initiator, and 1% (w/w) ethylene glycol dimethacrylate as cross-liking agent. Under these conditions, the moisture content of the polymerized SMA hydrogel was higher than in the other conditions. Moreover, the moisture content of the poly(SMA) hydrogel was also found to be higher than that of the poly(methyl methacrylate [MMA]) hydrogel. When the Fourier transform-infrared spectrum of poly(SMA) hydrogel was compared with that of poly(MMA) hydrogel, we noted a band at 1735-1730/cm, which did not appear in the Fourier transform-infrared spectrum of poly(MMA). The surface of the poly(SMA) hydrogel was visualized through scanning electron microscopy, and was uniform and clear in appearance.

Journal of medicinal chemistry, Jan 14, 2014

The aqueous solution structure of protoxin II (ProTx II) indicated that the toxin comprises a wel... more The aqueous solution structure of protoxin II (ProTx II) indicated that the toxin comprises a well-defined inhibitor cystine knot (ICK) backbone region and a flexible C-terminal tail region, similar to previously described NaSpTx III tarantula toxins. In the present study we sought to explore the structure−activity relationship of the two regions of the ProTx II molecule. As a first step, chimeric toxins of ProTx II and PaTx I were synthesized and their biological activities on Nav1.7 and Nav1.2 channels were investigated. Other tail region modifications to this chimera explored the effects of tail length and tertiary structure on sodium channel activity. In addition, the activity of various C-terminal modifications of the native ProTx II was assayed and resulted in the identification of protoxin II-NHCH 3 , a molecule with greater potency against Nav1.7 channels (IC 50 = 42 pM) than the original ProTx II.

Immunotherapies in CLL

Advances in experimental medicine and biology, 2013

Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed leukemia in the Western world... more Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed leukemia in the Western world, yet remains essentially incurable. Although initial chemotherapy response rates are high, patients invariably relapse and subsequently develop resistance to chemotherapy. For the moment, allogeneic hematopoietic stem cell transplant (allo-HSCT) remains the only potentially curative treatment for patients with CLL, but it is associated with high rates of treatment-related mortality. Immune-based treatment strategies to augment the cytotoxic potential of T cells offer exciting new treatment options for patients with CLL, and provide a unique and powerful spectrum of tools distinct from traditional chemotherapy. Among the most novel and promising of these approaches are chimeric antigen receptor (CAR)-based cell therapies that combine advances in genetic engineering and adoptive immunotherapy.

ATRA plus arsenic gets another "A" in APL

Blood, Jan 23, 2012

In this issue of Blood, Iland et al report that the addition of arsenic trioxide during induction... more In this issue of Blood, Iland et al report that the addition of arsenic trioxide during induction and consolidation can substantially reduce the amount of chemotherapy and the duration of consolidation to achieve excellent outcomes in patients with newly diagnosed acute promyelocytic leukemia (APL; see figure).

Cellular therapies in acute lymphoblastic leukemia

Hematology/oncology clinics of North America, 2011

ALL remains a difficult disease to treat. In the adult setting, most patients will ultimately die... more ALL remains a difficult disease to treat. In the adult setting, most patients will ultimately die of their disease, whereas in the pediatric setting, relapsed and refractory disease remains a therapeutic challenge. Cellular therapy through allo-HSCT remains an option for these patients, and recent advances in alternative forms of allo-HSCT, including unrelated donor transplants, UCB transplants, and haploidentical transplants, have expanded the numbers of patients eligible for allo-HSCT but have not improved outcomes when compared with HLA-matched related allo-HSCTs. In light of this persistent failure, several novel adoptive cellular approaches are being investigated to treat patients with ALL. The use of enriched WT-1–specific donor T cells to treat patients with ALL is currently under investigation in phase I trials at several centers. Treatment of ALL with genetically modified T cells targeted to the CD19 antigen through the expression of a CD19-specific CAR also have entered phase I clinical trials at several centers. Similarly, a clinical trial treating patients with ALL with genetically modified NK cells targeted to the CD19 antigen has recently opened for accrual. Collectively, these ongoing and anticipated trials provide a promising role for adoptive cellular therapies in the treatment of ALL. What remains to be seen is whether this promise will either translate into improved outcomes for these patients or provide significant insights on which to design second-generation adoptive cell therapeutic clinical trials for ALL in the future.

Are all chimeric antigen receptors created equal?

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 20, 2015

Targeted immunotherapy for hairy cell leukemia

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 20, 2012

Journal of peptide science : an official publication of the European Peptide Society, 2012

Protoxin II is biologically active peptide containing the inhibitory cystine knot motif. A synthe... more Protoxin II is biologically active peptide containing the inhibitory cystine knot motif. A synthetic version of the toxin was generated with standard Fmoc solid phase peptide synthesis. If N-methylmorpholine was used as a base during synthesis of the linear protoxin II, it was found that a significant amount of racemization (approximately 50%) was observed during the process of cysteine residue coupling. This racemization could be suppressed by substituting N-methylmorpholine with 2,4,6-collidine. The crude linear toxin was then air oxidized and purified. Electrophysiological assessment of the synthesized protoxin II confirmed its previously described interactions with voltage-gated sodium channels. Eight other naturally occurring inhibitory knot peptides were also synthesized using this same methodology. The inhibitory potencies of these synthesized toxins on Nav1.7 and Nav1.2 channels are summarized.

Burns : journal of the International Society for Burn Injuries, 2013

Blood, Jan 10, 2011

A 47-year-old man presented to his primary care physician with increasing fatigue and spontaneous... more A 47-year-old man presented to his primary care physician with increasing fatigue and spontaneous bruising. Laboratory evaluation revealed a white blood cell count (WBC) of 80 000/mm 3 , hematocrit of 25.6%, platelet count of 9000/mm 3 , and lactic dehydrogenase of 1075 U/L (reference range 110-210 U/L). He was immediately transferred to a local hospital. The peripheral blood smear showed predominantly myeloblasts with high nuclear:cytoplasm ratio, fine chromatin, prominent nucleoli, and numerous cells with an Auer rod. The platelets were significantly decreased in number and no nucleated red blood cells were identified. The bone marrow aspirate and biopsy revealed sheets of large blasts with fine chromatin and numerous Auer rods without normal hematopoiesis ( ). Immunophenotypic analysis of the blast population showed expression of CD13, CD19, CD33, CD34, CD117, and HLA-DR with partial expression of CD11b and CD33. The cytogenetic analysis demonstrated t(8;21)(q22;q22) in 20 of 20 metaphases examined. Molecular studies did not identify a FLT3 or NPM1 mutation. These findings were consistent with a diagnosis of core binding factor acute myeloid leukemia (CBF AML).

Oncology (Williston Park, N.Y.), 2011

Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia characterized by peculiar ... more Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia characterized by peculiar biologic features and a unique sensitivity to differentiation therapy with all-trans retinoic acid (ATRA). Modern treatment approaches to APL include simultaneous combination of ATRA and anthracycline-based chemotherapy. Gemtuzumab ozogamicin is a calicheamicin-conjugated monoclonal antibody directed against CD33, a cell surface antigen highly expressed on APL cells. Engagement of CD33 by gemtuzumab results in immunoconjugate internalization and hydrolytic release of calicheamicin, which, in turn, causes irreversible DNA damage and cell death. A number of preliminary reports have highlighted the sensitivity of APL to gemtuzumab given alone or in combination with other agents. Several reasons may account for the efficacy of gemtuzumab in APL, including: (1) CD33 is detectable in virtually 100% of APL cases; (2) calicheamicin belongs to the anthracycline family, a group of chemotherapeutic agents known to be highly effective in APL; and (3) the APL blast cells lack the multidrug resistance glycoprotein 170.

Emerging new approaches for the treatment of acute promyelocytic leukemia

Therapeutic advances in hematology, 2011

The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-... more The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-based chemotherapy has revolutionized the prognosis of acute promyelocytic leukemia (APL) with more than 90% complete response rates and cure rates of approximately 80%. The subsequent advent of arsenic trioxide (ATO) in 1990s and progress in the treatment of APL have changed its course from a highly fatal to a highly curable disease. Despite the dramatic improvement in clinical outcome of APL, treatment failure still occurs due most often to early death. Relapse has become increasingly less frequent, most commonly occurring in patients with high-risk disease. A major focus of research for the past decade has been to develop risk-adapted and rationally targeted nonchemotherapy treatment strategies to reduce treatment-related morbidity and mortality to low- and intermediate-risk or older patients while targeting more intensive or alternative therapy to those patients at most risk of relapse. In this review, emerging new approaches to APL treatment with special emhasis on strategies to reduce early deaths, risk-adapted therapy during induction, consolidation and maintenance, as well as an overview of current and future clinical trials in APL will be discussed.

Left behind: should minimal residual disease be treated in hairy cell leukemia?

Leukemia & lymphoma, 2014

American journal of hematology, 2007

We report a case of 64-year-old patient with pure red cell aplasia (PRCA) who was intolerant of c... more We report a case of 64-year-old patient with pure red cell aplasia (PRCA) who was intolerant of conventional immunosuppressive therapies but achieved a complete long-term remission following autologous hematologic stem cell transplant (HSCT). The patient was initially treated with high-dose prednisone, cyclophosphamide, cyclosporine, antithymocyte globulin, and then rituximab. With the exception of rituximab, all of the above regimens achieved a transient response. However, because of the persistent requirement for red blood cell transfusions and intolerance to the multiple immunosuppressive therapies, autologous HSCT was eventually performed. The patient remains in complete remission and on no other therapy for 36 months following the autologous HSCT. Am. J. Hematol. 82:812-814, 2007.

PloS one, 2014

Impaired ethanol metabolism can lead to various alcohol-related health problems. Key enzymes in e... more Impaired ethanol metabolism can lead to various alcohol-related health problems. Key enzymes in ethanol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); however, neuroendocrine pathways that regulate the activities of these enzymes are largely unexplored. Here we identified a neuroendocrine system involving Corazonin (Crz) neuropeptide and its receptor (CrzR) as important physiological regulators of ethanol metabolism in Drosophila. Crz-cell deficient (Crz-CD) flies displayed significantly delayed recovery from ethanol-induced sedation that we refer to as hangoverlike phenotype. Newly generated mutant lacking Crz Receptor (CrzR 01 ) and CrzR-knockdown flies showed even more severe hangover-like phenotype, which is causally associated with fast accumulation of acetaldehyde in the CrzR 01 mutant following ethanol exposure. Higher levels of acetaldehyde are likely due to 30% reduced ALDH activity in the mutants. Moreover, increased ADH activity was found in the CrzR 01 mutant, but not in the Crz-CD flies. Quantitative RT-PCR revealed transcriptional upregulation of Adh gene in the CrzR 01 . Transgenic inhibition of cyclic AMP-dependent protein kinase (PKA) also results in significantly increased ADH activity and Adh mRNA levels, indicating PKA-dependent transcriptional regulation of Adh by CrzR. Furthermore, inhibition of PKA or cAMP response element binding protein (CREB) in CrzR cells leads to comparable hangover-like phenotype to the CrzR 01 mutant. These findings suggest that CrzR-associated signaling pathway is critical for ethanol detoxification via Crz-dependent regulation of ALDH activity and Crz-independent transcriptional regulation of ADH. Our study provides new insights into the neuroendocrine-associated ethanol-related behavior and metabolism.

Engineering of Reconfigurable Systems and Algorithms, 2002

One property that distinguishes reconfigurable computing from rapid prototyping is the ability to... more One property that distinguishes reconfigurable computing from rapid prototyping is the ability to configure the computational fabric on-line while an application is running. Conventional reconfigurable computing platforms utilize commodity FPGAs, which typically have relatively long configuration times. Shrinking the configuration time down to the nanosecond region opens possibilities for rapid context switching and virtualizing the computational resources. An experimental context switching FPGA, called the CSRC, has been created by BAE Systems, and gives researchers the opportunity to explore context-switching applications. This paper presents results obtained from constructing both control-driven and data-driven context switching applications on the CSRC device, along with unique properties of the run-time and compile-time environment.

A Biomechanical Analysis System to Evaluate Physical Usability of Kimchi Refrigerator

Lecture Notes in Computer Science, 2007

ABSTRACT A biomechanical analysis system, consisting of measurement and analysis subsystems, were... more ABSTRACT A biomechanical analysis system, consisting of measurement and analysis subsystems, were developed and applied in evaluating the physical usability of a kimchi refrigerator. In the system, 3D motion measurement system and force platform system were used in measuring joint positions, ground reaction forces and moments. The systems also includes 3 analysis modules: kinematic, kinetic, and 3DSSPP analyses. Kimchi refrigerator, which is very popular as a specific refrigerator for kimchi, a Korean traditional dish, was evaluated using the system. The refrigerator is designed as a top-cover that makes the users feel uncomfortable in using it, though most people think it is a very useful product. The result showed it is possible to evaluate the physical usability of the refrigerator using the system effectively and reliably.

Performance Analysis of IEEE 802.11b Under Multiple IEEE 802.15.4 Interferences

Lecture Notes in Computer Science, 2007

ABSTRACT This paper presents analysis of the performance on the IEEE 802.11b in the presence of m... more ABSTRACT This paper presents analysis of the performance on the IEEE 802.11b in the presence of multiple IEEE 802.15.4 interferences. To analyze the performance, packet error rate (PER) and throughput are used as performance metrics. The PER is computed by the bit error rate (BER), the collision time and the number of IEEE 802.15.4 interferers in the presence of in-band of the IEEE 802.11b. The throughput of the IEEE 802.11b under multiple IEEE 802.15.4 interferences is obtained from the total IEEE 802.11b packet length received during a specified time. Analytic results of the performance of IEEE 802.11b under multiple IEEE 802.15.4 interferences are verified by simulation results. These results can support coexistence criteria for the IEEE 802.11b and the IEEE 802.15.4.

Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia

Science translational medicine, Jan 28, 2014

Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder characterized by somatic BRAF... more Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder characterized by somatic BRAFV600E mutations. The malignant cell in HCL has immunophenotypic features of a mature B cell, but no normal counterpart along the continuum of developing B lymphocytes has been delineated as the cell of origin. We find that the BRAFV600E mutation is present in hematopoietic stem cells (HSCs) in HCL patients, and that these patients exhibit marked alterations in hematopoietic stem/progenitor cell (HSPC) frequencies. Quantitative sequencing analysis revealed a mean BRAFV600E-mutant allele frequency of 4.97% in HSCs from HCL patients. Moreover, transplantation of BRAFV600E-mutant HSCs from an HCL patient into immunodeficient mice resulted in stable engraftment of BRAFV600E-mutant human hematopoietic cells, revealing the functional self-renewal capacity of HCL HSCs. Consistent with the human genetic data, expression of BRafV600E in murine HSPCs resulted in a lethal hematopoietic disorder characterized by splenomegaly, anemia, thrombocytopenia, increased circulating soluble CD25, and increased clonogenic capacity of B lineage cells-all classic features of human HCL. In contrast, restricting expression of BRafV600E to the mature B cell compartment did not result in disease. Treatment of HCL patients with vemurafenib, an inhibitor of mutated BRAF, resulted in normalization of HSPC frequencies and increased myeloid and erythroid output from HSPCs. These findings link the pathogenesis of HCL to somatic mutations that arise in HSPCs and further suggest that chronic lymphoid malignancies may be initiated by aberrant HSCs.

Three-dimensional blood vessel imaging using integral imaging

Biomedical Optics and 3-D Imaging, 2012

ABSTRACT Three-dimensional imaging of blood vessel using integral imaging technique is proposed. ... more ABSTRACT Three-dimensional imaging of blood vessel using integral imaging technique is proposed. With a near infrared illumination, a finger is imaged through a lens array and three-dimensional structure of the blood vessel in the finger is visualized.

Synthesis of Poly(Sorbitan Methacrylate) Hydrogel by Free-Radical Polymerization

Applied Biochemistry and Biotecnology, 2007

Hydrogels are materials with the ability to swell in water through the retention of significant f... more Hydrogels are materials with the ability to swell in water through the retention of significant fractions of water within their structures. Owing to their relatively high degree of biocompatibility, hydrogels have been utilized in a host of biomedical applications. In an attempt to determine the optimum conditions for hydrogel synthesis by the free-radical polymerization of sorbitan methacrylate (SMA), the hydrogel used in this study was well polymerized under the following conditions: 50% (w/v) SMA as monomer, 1% (w/w) alpha, alpha'-azo-bis(isobutyro-nitrile) as thermal initiator, and 1% (w/w) ethylene glycol dimethacrylate as cross-liking agent. Under these conditions, the moisture content of the polymerized SMA hydrogel was higher than in the other conditions. Moreover, the moisture content of the poly(SMA) hydrogel was also found to be higher than that of the poly(methyl methacrylate [MMA]) hydrogel. When the Fourier transform-infrared spectrum of poly(SMA) hydrogel was compared with that of poly(MMA) hydrogel, we noted a band at 1735-1730/cm, which did not appear in the Fourier transform-infrared spectrum of poly(MMA). The surface of the poly(SMA) hydrogel was visualized through scanning electron microscopy, and was uniform and clear in appearance.

Journal of medicinal chemistry, Jan 14, 2014

The aqueous solution structure of protoxin II (ProTx II) indicated that the toxin comprises a wel... more The aqueous solution structure of protoxin II (ProTx II) indicated that the toxin comprises a well-defined inhibitor cystine knot (ICK) backbone region and a flexible C-terminal tail region, similar to previously described NaSpTx III tarantula toxins. In the present study we sought to explore the structure−activity relationship of the two regions of the ProTx II molecule. As a first step, chimeric toxins of ProTx II and PaTx I were synthesized and their biological activities on Nav1.7 and Nav1.2 channels were investigated. Other tail region modifications to this chimera explored the effects of tail length and tertiary structure on sodium channel activity. In addition, the activity of various C-terminal modifications of the native ProTx II was assayed and resulted in the identification of protoxin II-NHCH 3 , a molecule with greater potency against Nav1.7 channels (IC 50 = 42 pM) than the original ProTx II.

Immunotherapies in CLL

Advances in experimental medicine and biology, 2013

Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed leukemia in the Western world... more Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed leukemia in the Western world, yet remains essentially incurable. Although initial chemotherapy response rates are high, patients invariably relapse and subsequently develop resistance to chemotherapy. For the moment, allogeneic hematopoietic stem cell transplant (allo-HSCT) remains the only potentially curative treatment for patients with CLL, but it is associated with high rates of treatment-related mortality. Immune-based treatment strategies to augment the cytotoxic potential of T cells offer exciting new treatment options for patients with CLL, and provide a unique and powerful spectrum of tools distinct from traditional chemotherapy. Among the most novel and promising of these approaches are chimeric antigen receptor (CAR)-based cell therapies that combine advances in genetic engineering and adoptive immunotherapy.

ATRA plus arsenic gets another "A" in APL

Blood, Jan 23, 2012

In this issue of Blood, Iland et al report that the addition of arsenic trioxide during induction... more In this issue of Blood, Iland et al report that the addition of arsenic trioxide during induction and consolidation can substantially reduce the amount of chemotherapy and the duration of consolidation to achieve excellent outcomes in patients with newly diagnosed acute promyelocytic leukemia (APL; see figure).

Cellular therapies in acute lymphoblastic leukemia

Hematology/oncology clinics of North America, 2011

ALL remains a difficult disease to treat. In the adult setting, most patients will ultimately die... more ALL remains a difficult disease to treat. In the adult setting, most patients will ultimately die of their disease, whereas in the pediatric setting, relapsed and refractory disease remains a therapeutic challenge. Cellular therapy through allo-HSCT remains an option for these patients, and recent advances in alternative forms of allo-HSCT, including unrelated donor transplants, UCB transplants, and haploidentical transplants, have expanded the numbers of patients eligible for allo-HSCT but have not improved outcomes when compared with HLA-matched related allo-HSCTs. In light of this persistent failure, several novel adoptive cellular approaches are being investigated to treat patients with ALL. The use of enriched WT-1–specific donor T cells to treat patients with ALL is currently under investigation in phase I trials at several centers. Treatment of ALL with genetically modified T cells targeted to the CD19 antigen through the expression of a CD19-specific CAR also have entered phase I clinical trials at several centers. Similarly, a clinical trial treating patients with ALL with genetically modified NK cells targeted to the CD19 antigen has recently opened for accrual. Collectively, these ongoing and anticipated trials provide a promising role for adoptive cellular therapies in the treatment of ALL. What remains to be seen is whether this promise will either translate into improved outcomes for these patients or provide significant insights on which to design second-generation adoptive cell therapeutic clinical trials for ALL in the future.

Are all chimeric antigen receptors created equal?

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 20, 2015

Targeted immunotherapy for hairy cell leukemia

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 20, 2012

Journal of peptide science : an official publication of the European Peptide Society, 2012

Protoxin II is biologically active peptide containing the inhibitory cystine knot motif. A synthe... more Protoxin II is biologically active peptide containing the inhibitory cystine knot motif. A synthetic version of the toxin was generated with standard Fmoc solid phase peptide synthesis. If N-methylmorpholine was used as a base during synthesis of the linear protoxin II, it was found that a significant amount of racemization (approximately 50%) was observed during the process of cysteine residue coupling. This racemization could be suppressed by substituting N-methylmorpholine with 2,4,6-collidine. The crude linear toxin was then air oxidized and purified. Electrophysiological assessment of the synthesized protoxin II confirmed its previously described interactions with voltage-gated sodium channels. Eight other naturally occurring inhibitory knot peptides were also synthesized using this same methodology. The inhibitory potencies of these synthesized toxins on Nav1.7 and Nav1.2 channels are summarized.

Burns : journal of the International Society for Burn Injuries, 2013

Blood, Jan 10, 2011

A 47-year-old man presented to his primary care physician with increasing fatigue and spontaneous... more A 47-year-old man presented to his primary care physician with increasing fatigue and spontaneous bruising. Laboratory evaluation revealed a white blood cell count (WBC) of 80 000/mm 3 , hematocrit of 25.6%, platelet count of 9000/mm 3 , and lactic dehydrogenase of 1075 U/L (reference range 110-210 U/L). He was immediately transferred to a local hospital. The peripheral blood smear showed predominantly myeloblasts with high nuclear:cytoplasm ratio, fine chromatin, prominent nucleoli, and numerous cells with an Auer rod. The platelets were significantly decreased in number and no nucleated red blood cells were identified. The bone marrow aspirate and biopsy revealed sheets of large blasts with fine chromatin and numerous Auer rods without normal hematopoiesis ( ). Immunophenotypic analysis of the blast population showed expression of CD13, CD19, CD33, CD34, CD117, and HLA-DR with partial expression of CD11b and CD33. The cytogenetic analysis demonstrated t(8;21)(q22;q22) in 20 of 20 metaphases examined. Molecular studies did not identify a FLT3 or NPM1 mutation. These findings were consistent with a diagnosis of core binding factor acute myeloid leukemia (CBF AML).

Oncology (Williston Park, N.Y.), 2011

Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia characterized by peculiar ... more Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia characterized by peculiar biologic features and a unique sensitivity to differentiation therapy with all-trans retinoic acid (ATRA). Modern treatment approaches to APL include simultaneous combination of ATRA and anthracycline-based chemotherapy. Gemtuzumab ozogamicin is a calicheamicin-conjugated monoclonal antibody directed against CD33, a cell surface antigen highly expressed on APL cells. Engagement of CD33 by gemtuzumab results in immunoconjugate internalization and hydrolytic release of calicheamicin, which, in turn, causes irreversible DNA damage and cell death. A number of preliminary reports have highlighted the sensitivity of APL to gemtuzumab given alone or in combination with other agents. Several reasons may account for the efficacy of gemtuzumab in APL, including: (1) CD33 is detectable in virtually 100% of APL cases; (2) calicheamicin belongs to the anthracycline family, a group of chemotherapeutic agents known to be highly effective in APL; and (3) the APL blast cells lack the multidrug resistance glycoprotein 170.

Emerging new approaches for the treatment of acute promyelocytic leukemia

Therapeutic advances in hematology, 2011

The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-... more The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-based chemotherapy has revolutionized the prognosis of acute promyelocytic leukemia (APL) with more than 90% complete response rates and cure rates of approximately 80%. The subsequent advent of arsenic trioxide (ATO) in 1990s and progress in the treatment of APL have changed its course from a highly fatal to a highly curable disease. Despite the dramatic improvement in clinical outcome of APL, treatment failure still occurs due most often to early death. Relapse has become increasingly less frequent, most commonly occurring in patients with high-risk disease. A major focus of research for the past decade has been to develop risk-adapted and rationally targeted nonchemotherapy treatment strategies to reduce treatment-related morbidity and mortality to low- and intermediate-risk or older patients while targeting more intensive or alternative therapy to those patients at most risk of relapse. In this review, emerging new approaches to APL treatment with special emhasis on strategies to reduce early deaths, risk-adapted therapy during induction, consolidation and maintenance, as well as an overview of current and future clinical trials in APL will be discussed.

Left behind: should minimal residual disease be treated in hairy cell leukemia?

Leukemia & lymphoma, 2014

American journal of hematology, 2007

We report a case of 64-year-old patient with pure red cell aplasia (PRCA) who was intolerant of c... more We report a case of 64-year-old patient with pure red cell aplasia (PRCA) who was intolerant of conventional immunosuppressive therapies but achieved a complete long-term remission following autologous hematologic stem cell transplant (HSCT). The patient was initially treated with high-dose prednisone, cyclophosphamide, cyclosporine, antithymocyte globulin, and then rituximab. With the exception of rituximab, all of the above regimens achieved a transient response. However, because of the persistent requirement for red blood cell transfusions and intolerance to the multiple immunosuppressive therapies, autologous HSCT was eventually performed. The patient remains in complete remission and on no other therapy for 36 months following the autologous HSCT. Am. J. Hematol. 82:812-814, 2007.

PloS one, 2014

Impaired ethanol metabolism can lead to various alcohol-related health problems. Key enzymes in e... more Impaired ethanol metabolism can lead to various alcohol-related health problems. Key enzymes in ethanol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); however, neuroendocrine pathways that regulate the activities of these enzymes are largely unexplored. Here we identified a neuroendocrine system involving Corazonin (Crz) neuropeptide and its receptor (CrzR) as important physiological regulators of ethanol metabolism in Drosophila. Crz-cell deficient (Crz-CD) flies displayed significantly delayed recovery from ethanol-induced sedation that we refer to as hangoverlike phenotype. Newly generated mutant lacking Crz Receptor (CrzR 01 ) and CrzR-knockdown flies showed even more severe hangover-like phenotype, which is causally associated with fast accumulation of acetaldehyde in the CrzR 01 mutant following ethanol exposure. Higher levels of acetaldehyde are likely due to 30% reduced ALDH activity in the mutants. Moreover, increased ADH activity was found in the CrzR 01 mutant, but not in the Crz-CD flies. Quantitative RT-PCR revealed transcriptional upregulation of Adh gene in the CrzR 01 . Transgenic inhibition of cyclic AMP-dependent protein kinase (PKA) also results in significantly increased ADH activity and Adh mRNA levels, indicating PKA-dependent transcriptional regulation of Adh by CrzR. Furthermore, inhibition of PKA or cAMP response element binding protein (CREB) in CrzR cells leads to comparable hangover-like phenotype to the CrzR 01 mutant. These findings suggest that CrzR-associated signaling pathway is critical for ethanol detoxification via Crz-dependent regulation of ALDH activity and Crz-independent transcriptional regulation of ADH. Our study provides new insights into the neuroendocrine-associated ethanol-related behavior and metabolism.

Engineering of Reconfigurable Systems and Algorithms, 2002

One property that distinguishes reconfigurable computing from rapid prototyping is the ability to... more One property that distinguishes reconfigurable computing from rapid prototyping is the ability to configure the computational fabric on-line while an application is running. Conventional reconfigurable computing platforms utilize commodity FPGAs, which typically have relatively long configuration times. Shrinking the configuration time down to the nanosecond region opens possibilities for rapid context switching and virtualizing the computational resources. An experimental context switching FPGA, called the CSRC, has been created by BAE Systems, and gives researchers the opportunity to explore context-switching applications. This paper presents results obtained from constructing both control-driven and data-driven context switching applications on the CSRC device, along with unique properties of the run-time and compile-time environment.

A Biomechanical Analysis System to Evaluate Physical Usability of Kimchi Refrigerator

Lecture Notes in Computer Science, 2007

ABSTRACT A biomechanical analysis system, consisting of measurement and analysis subsystems, were... more ABSTRACT A biomechanical analysis system, consisting of measurement and analysis subsystems, were developed and applied in evaluating the physical usability of a kimchi refrigerator. In the system, 3D motion measurement system and force platform system were used in measuring joint positions, ground reaction forces and moments. The systems also includes 3 analysis modules: kinematic, kinetic, and 3DSSPP analyses. Kimchi refrigerator, which is very popular as a specific refrigerator for kimchi, a Korean traditional dish, was evaluated using the system. The refrigerator is designed as a top-cover that makes the users feel uncomfortable in using it, though most people think it is a very useful product. The result showed it is possible to evaluate the physical usability of the refrigerator using the system effectively and reliably.

Performance Analysis of IEEE 802.11b Under Multiple IEEE 802.15.4 Interferences

Lecture Notes in Computer Science, 2007

ABSTRACT This paper presents analysis of the performance on the IEEE 802.11b in the presence of m... more ABSTRACT This paper presents analysis of the performance on the IEEE 802.11b in the presence of multiple IEEE 802.15.4 interferences. To analyze the performance, packet error rate (PER) and throughput are used as performance metrics. The PER is computed by the bit error rate (BER), the collision time and the number of IEEE 802.15.4 interferers in the presence of in-band of the IEEE 802.11b. The throughput of the IEEE 802.11b under multiple IEEE 802.15.4 interferences is obtained from the total IEEE 802.11b packet length received during a specified time. Analytic results of the performance of IEEE 802.11b under multiple IEEE 802.15.4 interferences are verified by simulation results. These results can support coexistence criteria for the IEEE 802.11b and the IEEE 802.15.4.

Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia

Science translational medicine, Jan 28, 2014

Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder characterized by somatic BRAF... more Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder characterized by somatic BRAFV600E mutations. The malignant cell in HCL has immunophenotypic features of a mature B cell, but no normal counterpart along the continuum of developing B lymphocytes has been delineated as the cell of origin. We find that the BRAFV600E mutation is present in hematopoietic stem cells (HSCs) in HCL patients, and that these patients exhibit marked alterations in hematopoietic stem/progenitor cell (HSPC) frequencies. Quantitative sequencing analysis revealed a mean BRAFV600E-mutant allele frequency of 4.97% in HSCs from HCL patients. Moreover, transplantation of BRAFV600E-mutant HSCs from an HCL patient into immunodeficient mice resulted in stable engraftment of BRAFV600E-mutant human hematopoietic cells, revealing the functional self-renewal capacity of HCL HSCs. Consistent with the human genetic data, expression of BRafV600E in murine HSPCs resulted in a lethal hematopoietic disorder characterized by splenomegaly, anemia, thrombocytopenia, increased circulating soluble CD25, and increased clonogenic capacity of B lineage cells-all classic features of human HCL. In contrast, restricting expression of BRafV600E to the mature B cell compartment did not result in disease. Treatment of HCL patients with vemurafenib, an inhibitor of mutated BRAF, resulted in normalization of HSPC frequencies and increased myeloid and erythroid output from HSPCs. These findings link the pathogenesis of HCL to somatic mutations that arise in HSPCs and further suggest that chronic lymphoid malignancies may be initiated by aberrant HSCs.

Three-dimensional blood vessel imaging using integral imaging

Biomedical Optics and 3-D Imaging, 2012

ABSTRACT Three-dimensional imaging of blood vessel using integral imaging technique is proposed. ... more ABSTRACT Three-dimensional imaging of blood vessel using integral imaging technique is proposed. With a near infrared illumination, a finger is imaged through a lens array and three-dimensional structure of the blood vessel in the finger is visualized.