Evolution of DNA replication origin specification and gene silencing mechanisms.

DNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove. Using a massively parallel origin selection assay coupled with a custom mutual-information-based modeling approach, and a separate analysis of whole-genome replication profiling, here we show that the Orc4 α-helix contributes to the DNA sequence-specificity of origins in S. cerevisiae and Orc4 α-helix mutations change genome-wide origin firing patterns. The DNA sequence specificity of replication origins, mediated by the Orc4 α-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference.

Application of γ-PGA as the primary carbon source to bioremediate a TCE-polluted aquifer: A pilot-scale study.

The effectiveness of using gamma poly-glutamic acid (γ-PGA) as the primary carbon and nitrogen sources to bioremediate trichloroethene (TCE)-contaminated groundwater was studied in this pilot-scale study. γ-PGA (40 L) solution was injected into the aquifer via the injection well (IW) for substrate supplement. Groundwater samples were collected from monitor wells and IW and analyzed for TCE and its byproducts, geochemical indicators, dechlorinating bacteria, and microbial diversity periodically. Injected γ-PGA resulted in an increase in total organic carbon (TOC) (up to 9820 mg/L in IW), and the TOC biodegradation caused the formation of anaerobic conditions. Increased ammonia concentration (because of amine release from γ-PGA) resulted in the neutral condition in groundwater, which benefited the growth of Dehalococcoides. The negative zeta potential and micro-scale diameter of γ-PGA allowed its globule to distribute evenly within soil pores. Up to 93% of TCE removal was observed (TCE dropped from 0.14 to 0.01 mg/L) after 59 days of γ-PGA injection, and TCE dechlorination byproducts were also biodegraded subsequently. Next generation sequence (NGS) analyses were applied to determine the dominant bacterial communities. γ-PGA supplement developed reductive dechlorinating conditions and caused variations in microbial diversity and dominant bacterial species. The dominant four groups of bacterial communities including dechlorinating bacteria, vinyl chloride degrading bacteria, hydrogen producing bacteria, and carbon biodegrading bacteria.

Emulsified polycolloid substrate biobarrier for benzene and petroleum-hydrocarbon plume containment and migration control - A field-scale study.

The objective of this field-scale study was to assess the effectiveness of applying an emulsified polycolloid substrate (EPS; containing cane molasses, soybean oil, and surfactants) biobarrier in the control and remediation of a petroleum-hydrocarbon plume in natural waters. An abandoned petrochemical manufacturing facility site was contaminated by benzene and other petroleum products due to a leakage from a storage tank. Because benzene is a petroleum hydrocarbon with a high migration ability, it was used as the target compound in the field-scale study. Batch partition and sorption experiment results indicated that the EPS to water partition coefficient for benzene was 232 mg/mg at 25 °C. This suggests that benzene had a higher sorption affinity to EPS, which decreased the benzene concentrations in groundwater. The EPS solution was pressure-injected into three remediation wells (RWs; 150 L EPS in 800 L groundwater). Groundwater samples were collected from an upgradient background well, two downgradient monitor wells (MWs), and the three RWs for analyses. EPS injection increased total organic carbon (TOC) concentrations (up to 786 mg/L) in groundwater, which also resulted in the formation of anaerobic conditions. An abrupt drop in benzene concentration (from 6.9 to below 0.04 mg/L) was observed after EPS supplementation in the RWs due to both sorption and biodegradation mechanisms. Results show that the EPS supplement increased total viable bacteria and enhanced bioremediation efficiency, which accounted for the observed decrease in benzene concentration. The first-order decay rate in RW1 increased from 0.003 to 0.023 d-1 after EPS application. Injection of EPS resulted in significant growth of indigenous bacteria, and 23 petroleum-hydrocarbon-degrading bacterial species were detected, which enhanced the in situ benzene biodegradation efficiency. Results demonstrate that the EPS biobarrier can effectively contain a petroleum-hydrocarbon plume and prevent its migration to downgradient areas, which reduces the immediate risk presented to downgradient receptors.

Application of an emulsified polycolloid substrate biobarrier to remediate petroleum-hydrocarbon contaminated groundwater.

Emulsified polycolloid substrate (EPS) was developed and applied in situ to form a biobarrier for the containment and enhanced bioremediation of a petroleum-hydrocarbon plume. EPS had a negative zeta potential (-35.7 mv), which promoted its even distribution after injection. Batch and column experiments were performed to evaluate the effectiveness of EPS on toluene containment and biodegradation. The EPS-to-water partition coefficient for toluene (target compound) was 943. Thus, toluene had a significant sorption affinity to EPS, which caused reduced toluene concentration in water phase in the EPS/water system. Groundwater containing toluene (18 mg/L) was pumped into the three-column system at a flow rate of 0.28 mL/min, while EPS was injected into the second column to form a biobarrier. A significant reduction of toluene concentration to 0.1 mg/L was observed immediately after EPS injection. This indicates that EPS could effectively contain toluene plume and prevent its further migration to farther downgradient zone. Approximately 99% of toluene was removed after 296 PVs of operation via sorption, natural attenuation, and EPS-enhanced biodegradation. Increase in total organic carbon and bacteria were also observed after EPS supplement. Supplement of EPS resulted in a growth of petroleum-hydrocarbon degrading bacteria, which enhanced the toluene biodegradation.

Genetic diversity of Bromeliaceae species from the Atlantic Forest.

The Bromeliaceae family includes a range of species used for many purposes, including ornamental use and use as food, medicine, feed, and fiber. The state of Espírito Santo, Brazil is a center of diversity for this family in the Atlantic Forest. We evaluated the genetic diversity of five populations of the Bromeliaceae family, including specimens of the genera Aechmea, Billbergia (subfamily Bromelioideae), and Pitcairnia (subfamily Pitcairnioidea), all found in the Atlantic Forest and distributed in the state of Espírito Santo. The number of alleles per locus in populations ranged from two to six and the fixation index (F), estimated for some simple sequence repeats in bromeliad populations, was less than zero in all populations. All markers in the Pitcairnia flammea population were in Hardy-Weinberg equilibrium (P < 0.05). Moreover, significant deviations from Hardy-Weinberg equilibrium were observed at some loci in populations of the five bromeliad species. In most cases, this can be attributed to the presence of inbreeding or the Wahlund effect. The genetic diversity indices of five species showed greater allelic richness in P. flammea (3.55). Therefore, we provide useful information for the characterization of genetic diversity in natural populations of Aechmea ramosa, Aechmea nudicaulis, Billbergia horrid, Billbergia euphemia, and P. flammea in Atlantic Forest remnants in the south of Espírito Santo state.

Application of a long-lasting colloidal substrate with pH and hydrogen sulfide control capabilities to remediate TCE-contaminated groundwater.

A long-lasting emulsified colloidal substrate (LECS) was developed for continuous carbon and nanoscale zero-valent iron (nZVI) release to remediate trichloroethylene (TCE)-contaminated groundwater under reductive dechlorinating conditions. The developed LECS contained nZVI, vegetable oil, surfactants (Simple Green™ and lecithin), molasses, lactate, and minerals. An emulsification study was performed to evaluate the globule droplet size and stability of LECS. The results show that a stable oil-in-water emulsion with uniformly small droplets (0.7 µm) was produced, which could continuously release the primary substrates. The emulsified solution could serve as the dispensing agent, and nZVI particles (with diameter 100-200 nm) were distributed in the emulsion evenly without aggregation. Microcosm results showed that the LECS caused a rapid increase in the total organic carbon concentration (up to 488 mg/L), and reductive dechlorination of TCE was significantly enhanced. Up to 99% of TCE (with initial concentration of 7.4 mg/L) was removed after 130 days of operation. Acidification was prevented by the production of hydroxide ion by the oxidation of nZVI. The formation of iron sulfide reduced the odor from produced hydrogen sulfide. Microbial analyses reveal that dechlorinating bacteria existed in soils, which might contribute to TCE dechlorination.

Using ultrashort optical pulses to couple ferroelectric and ferromagnetic order in an oxide heterostructure.

A new approach to all-optical detection and control of the coupling between electric and magnetic order on ultrafast timescales is achieved using time-resolved second-harmonic generation (SHG) to study a ferroelectric (FE)/ferromagnet (FM) oxide heterostructure. We use femtosecond optical pulses to modify the spin alignment in a Ba(0.1)Sr(0.9)TiO3 (BSTO)/La(0.7)Ca(0.3)MnO3 (LCMO) heterostructure and selectively probe the ferroelectric response using SHG. In this heterostructure, the pump pulses photoexcite non-equilibrium quasiparticles in LCMO, which rapidly interact with phonons before undergoing spin-lattice relaxation on a timescale of tens of picoseconds. This reduces the spin-spin correlations in LCMO, applying stress on BSTO through magnetostriction. This then modifies the FE polarization through the piezoelectric effect, on a timescale much faster than laser-induced heat diffusion from LCMO to BSTO. We have thus demonstrated an ultrafast indirect magnetoelectric effect in a FE/FM heterostructure mediated through elastic coupling, with a timescale primarily governed by spin-lattice relaxation in the FM layer.

Bone-muscle indices as risk factors for fractures in men: the Osteoporotic Fractures in Men (MrOS) Study.

OBJECTIVE: To assess bone-muscle (B-M) indices as risk factors for incident fractures in men. METHODS: Participants of the Osteoporotic Fractures in Men (MrOS) Study completed a peripheral quantitative computed tomography scan at 66% of their tibial length. Bone macrostructure, estimates of bone strength, and muscle area were computed. Areal bone mineral density (aBMD) and body composition were assessed with dual-energy X-ray absorptiometry. Four year incident non-spine and clinical vertebral fractures were ascertained. B-M indices were expressed as bone-to-muscle ratios for: strength, mass and area. Discriminative power and hazards ratios (HR) for fractures were reported. RESULTS: In 1163 men (age: 77.2±5.2 years, body mass index (BMI): 28.0±4.0 kg/m(2), 4.1±0.9 follow-up years, 7.7% of men ⋝1 fracture), B-M indices were smaller in fractured men except for bending and areal indices. Smaller B-M indices were associated with increased fracture risk (HR: 1.30 to 1.74) independent of age and BMI. Strength and mass indices remained significant after accounting for lumbar spine but not total hip aBMD. However, aBMD correlated significantly with B-M indices. CONCLUSION: Mass and bending B-M indices are risk factors for fractures in men, but may not improve fracture risk prediction beyond that provided by total hip aBMD.

Race/ethnic differences in associations between bone mineral density and fracture history in older men.

SUMMARY: To determine whether there are race/ethnic differences in bone mineral density (BMD) by fracture history in men aged 65 years and older, we performed cross-sectional analysis in five large independent cohorts. Low BMD was associated with a higher prevalence of fracture in all cohorts, and the magnitude of the BMD differences by fracture status was similar across groups. INTRODUCTION: We aimed to determine whether there are race/ethnic and geographic differences in bone mineral density by fracture history in men aged 65 years and older. METHOD: The datasets included the Osteoporotic Fractures in Men (MrOS) Study (5,342 White, 243 African-American, 190 Asian, and 126 Hispanic), MrOS Hong Kong (1,968 Hong Kong Chinese), Tobago Bone Health Study (641 Afro-Caribbean), Namwon Study (1,834 Korean), and Dong-gu Study (2,057 Korean). The two Korean cohorts were combined. RESULTS: The prevalence of self-reported non-traumatic fracture was US white, 17.1 %; Afro-Caribbean, 5.5 %; US African-American, 15.1 %; US Hispanic, 13.7 %; US Asian, 10.5 %; Hong Kong Chinese, 5.6 %, and Korean, 5.1 %. The mean differences in hip and lumbar spine BMD between subjects with fracture and without fracture were statistically significant in all cohorts except US African American and US Asian men. There was a significant race/ethnic interaction for lumbar spine BMD by fracture status (p for interaction = 0.02), which was driven by the small number of Hispanic men. There was no interaction for femoral neck or total hip BMD. There were no significant race/ethnic differences in the odds ratio of fracture by BMD. CONCLUSIONS: Low BMD was associated with a higher prevalence of fracture in all cohorts and the magnitude of the BMD differences by fracture status was similar across groups suggesting homogeneity in the BMD-fracture relationship among older men.

Skeletal muscle adiposity is associated with serum lipid and lipoprotein levels in Afro-Caribbean men.

OBJECTIVE: When compared with other ethnic groups, African ancestry individuals have lower triglycerides and higher High-density lipoprotein cholesterol (HDL-C) levels, although the mechanisms for these differences remain unclear. A comprehensive array of factors potentially related to fasting serum lipid and lipoprotein levels in African ancestry men was evaluated. DESIGN AND METHODS: Men (1,821) underwent dual-energy X-ray absorptiometry measures of total body fat and quantitative computed tomography assessments of calf skeletal muscle adiposity [subcutaneous and intermuscular adipose tissue (AT), and muscle density as a measure of intra-muscular AT]. RESULTS: Multivariable linear regression analysis identified age (-), total body fat (+), subcutaneous AT (-), fasting glucose (+), fasting insulin (+), diastolic blood pressure (+), and non-African ancestry (+) as independent correlates of triglycerides (all P < 0.05). Total body fat (+), intra-muscular AT (-), and diastolic blood pressure (+) were independent correlates of Low-density lipoprotein cholesterol (LDL-C) (all P < 0.001). Age (+), waist circumference (-), fasting insulin (-), physical activity (+), and alcohol intake (+) were independent correlates of HDL-C (all P < 0.05). CONCLUSIONS: A novel relationship between skeletal muscle adiposity and serum lipid and lipoprotein levels in African ancestry men, independent of total and central adiposity was illuminated. In African ancestry populations, genetic factors are likely a significant determinant of triglycerides levels.

Abdominal body composition measured by quantitative computed tomography and risk of non-spine fractures: the Osteoporotic Fractures in Men (MrOS) Study.

UNLABELLED: The effect of abdominal adiposity and muscle on fracture is unclear in older men; therefore, we examined the association among 749 men aged 65+. Among various adipose tissues and muscle groups, lower psoas muscle volume and higher fatty infiltration of abdominal muscle contribute to higher fracture risk independent of BMD. INTRODUCTION: The association of abdominal adiposity and muscle composition with incident fracture is unclear, especially in older men. Therefore, we examined the relationship of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal intermuscular adipose tissue (IMAT), and muscle volume with incident non-spine fractures among 749 men aged 65 and older. METHODS: A case-cohort study design was used with a total of 252 fracture cases and 497 non-cases. We measured volumes (in centimeters) of adipose and muscle tissues obtained from quantitative computed tomography scan at the L4-5 intervertebral space. Three groups of muscle and IMAT were evaluated: total abdominal, psoas, and paraspinal. Cox proportional hazards regression with a robust variance estimator was used to estimate the hazard ratio (HR) of non-spine fractures per standard deviation (SD) increase in the abdominal body composition measures. The mean age among men in the random subcohort was 74.2 ± 6.1 years, and the average follow-up time was 5.2 ± 1.1 years. RESULTS: After adjusting for age, race, clinic site, percent body fat, and femoral neck bone mineral density (BMD), no significant relationship was found between incident fractures and SAT or VAT. One SD increase in muscle volume at the psoas, but not paraspinal, was associated with 28 % lower fracture risk (95 % CI = 0.55-0.95). When IMAT models were further adjusted for corresponding muscle volumes, only abdominal IMAT was significantly associated with fracture risk (HR = 1.30 (95 % CI = 1.04-1.63)). CONCLUSION: Our findings suggest that lower total psoas muscle volume and higher IMAT of the total abdominal muscle contribute to higher fracture risk in older men independent of BMD.

The revised Atlanta classification for acute pancreatitis: a CT imaging guide for radiologists.

Accurate diagnosis and description of the various findings in acute pancreatitis is important for treatment. The original Atlanta classification for acute pancreatitis sought to create a uniform system for classifying the severity of acute pancreatitis as well as common language to describe the various events that can occur in acute pancreatitis. The goal was to allow accurate communication between physicians using standardized language so correct treatment options could be used. Since that time, advances in the understanding of acute pancreatitis as well as improvements in both interventions and imaging have led to criticisms of the system and its abandonment by physicians. A 2007 revision of the Atlanta classifications sought to address many of these issues. This article will explain the changes to the Atlanta classification system and provide pictorial examples of the findings in acute pancreatitis as described by the Atlanta classification system.

Age-related decline in bone density among ethnically diverse older men.

UNLABELLED: We compared rates of BMD decline in older men of diverse ethnic background. The rate of bone loss was statistically equivalent between men of African and Caucasian descent. INTRODUCTION: Race differences in peak bone mineral density (BMD) are well established, but the magnitude of bone loss among non-white men has not been well characterized. Our objective was to compare and contrast the rates of decline in BMD with aging among older men of different race/ethnic groups. METHODS: The rate of decline in hip BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR-4500 W) with an average follow-up of 4.6 years in 3,869 Caucasian, 138 African American, 145 Asian, and 334 Afro-Caribbean men aged ≥ 65 years (Mean ages: 73 ± 5, 70 ± 4, 72 ± 5, 71 ± 5 years, respectively). RESULTS: The annual rate of decline in BMD at the femoral neck was -0.32%, -0.42%, -0.09%, and -0.44%/year for Caucasian, African American, Asian, and Afro-Caribbean men, respectively (p < 0.05 for Caucasian versus Asian). Although men of African ancestry have higher peak BMD than Caucasians, rates of decline in BMD with aging appear to be statistically equivalent in our study. In contrast, Asian men experienced a slower rate of decline in BMD compared with Caucasians and African Americans. CONCLUSION: More studies are needed to better define the natural history of and factors associated with bone loss among non-white men.

Imaging nonequilibrium atomic vibrations with x-ray diffuse scattering.

We use picosecond x-ray diffuse scattering to image the nonequilibrium vibrations in the lattice following ultrafast laser excitation. We present images of nonequilibrium phonons in InP and InSb throughout the Brillouin zone which remain out of equilibrium up to nanoseconds. The results are analyzed using a Born model that helps identify the phonon branches contributing to the observed features in the time-resolved diffuse scattering. In InP this analysis shows a delayed increase in the transverse-acoustic (TA) phonon population along high-symmetry directions accompanied by a decrease in the longitudinal-acoustic phonons. In InSb the increase in TA phonon population is less directional.

Probing unfolded acoustic phonons with X rays.

Ultrafast laser excitation of an InGaAs/InAlAs superlattice (SL) creates coherent folded acoustic phonons that subsequently leak into the bulk (InP) substrate. Upon transmission, the phonons become "unfolded" into bulk modes and acquire a wave vector much larger than that of the light. We show that time-resolved x-ray diffraction is sensitive to this large-wave vector excitation in the substrate. Comparison with dynamical diffraction simulations of propagating strain supports our interpretation.

Correlates of bone mineral density in men of African ancestry: the Tobago bone health study.

UNLABELLED: Correlates of BMD were examined in a cross-sectional analysis of men of West African ancestry. BMD, measured at the total hip and the femoral neck subregion, was associated with age, anthropometric, lifestyle, and medical factors in multiple linear regression models. These models explained 25-27% of the variability in total hip and femoral neck BMD, respectively, and 13% of the variability in estimated volumetric BMD. OBJECTIVE: To examine the correlates of bone mineral density (BMD) in men of West African ancestry. METHODS: Two thousand five hundred and one men aged 40 to 93 years were recruited from the Caribbean Island of Tobago. Participants completed a questionnaire and physical examination. We measured hip BMD and body composition, using DXA. Volumetric BMD was estimated as bone mineral apparent density (BMAD). RESULTS: BMD was 10% and 20% higher in African Caribbean males compared to U.S. non-Hispanic black and white males, respectively. In multiple linear regression models, greater lean mass, history of working on a fishing boat or on a farm, frequent walking, and self-reported diabetes were significantly associated with higher BMD. Fat mass, history of farming, and self-reported hypertension were also associated with higher BMAD. Older age, mixed African ancestry, and history of a fracture were associated with lower BMD and BMAD. Lean body mass explained 20%, 18% and 6% of the variance in BMD at the total hip, femoral neck and BMAD, respectively. CONCLUSIONS: African Caribbean males have the highest BMD on a population level ever reported. Lean mass was the single most important correlate. Variability in BMD/BMAD was also explained by age, mixed African ancestry, anthropometric, lifestyle, and medical factors.

The search for human osteoporosis genes.

Osteoporosis is the most prevalent metabolic bone disease and a major clinical and public health problem. Heredity plays an important and well-established role in determining the lifetime risk of this disease. Major efforts are currently underway to identify the specific genes and their allelic variations that contribute to the heritable component to osteoporosis. A number of laboratories are using quantitative trait locus (QTL) methods of genome scanning in families and animal models to identify candidate genomic regions and, ultimately, the genes and genetic variations that lead to osteoporosis. Several chromosomal regions of the human genome have now been linked to osteoporosis-related phenotypes. Although the specific genes contributing to the majority of these linkage signals have not been identified, two positional candidate genes have now been identified: low density lipoprotein receptor-related protein 5 (LRP5) and bone morphogenetic protein 2 (BMP2). A number of QTL has also been identified by cross-breeding strains of mice with variable bone density and several of these QTL have been fine mapped, providing a rich new base for understanding osteoporosis. Genetic association analyses have also provided evidence for a modest relationship between allelic variants in several biological candidate genes and bone mass and the risk of fracture. These ongoing animal and human studies will provide a continuing source of new insight into the genetic regulation of bone and mineral metabolism and the molecular etiology of osteoporosis. The new insight that will emerge from this ongoing research should lead to new ways of diagnosing, preventing and treating the growing clinical and public health problem of osteoporosis.

Spermatozoan morphology of four species of bivalve (Heterodonta, Veneridae) from Taiwan.

Using transmission and scanning electron microscopy, the mature spermatozoa of four bivalves of the family Veneridae--Gafrarium tumidum and Circe scripta (Circinae), Pitar sulfureum (Pitarinae) and Gomphina aequilatera (Tapetinae)--are described for the first time and compared with those of other bivalves, particularly other heterodonts. As our observations show, the spermatozoa of these four species are of the primitive type or ect-aquasperm form. The head contains a slightly curved nucleus with a short cone-shaped acrosome. The structure of the acrosome is typical of heterodont bivalves and two major components of the acrosomal vesicle material can be distinguished. The midpiece exhibits four or five mitochondria which surround the proximal and the distal centrioles. Variation in the shape and dimensions of the acrosomal vesicle and nucleus is substantial in these four Veneroidea species.

Polarized growth controls cell shape and bipolar bud site selection in Saccharomyces cerevisiae.

We examined the relationship between polarized growth and division site selection, two fundamental processes important for proper development of eukaryotes. Diploid Saccharomyces cerevisiae cells exhibit an ellipsoidal shape and a specific division pattern (a bipolar budding pattern). We found that the polarity genes SPA2, PEA2, BUD6, and BNI1 participate in a crucial step of bud morphogenesis, apical growth. Deleting these genes results in round cells and diminishes bud elongation in mutants that exhibit pronounced apical growth. Examination of distribution of the polarized secretion marker Sec4 demonstrates that spa2Delta, pea2Delta, bud6Delta, and bni1Delta mutants fail to concentrate Sec4 at the bud tip during apical growth and at the division site during repolarization just prior to cytokinesis. Moreover, cell surface expansion is not confined to the distal tip of the bud in these mutants. In addition, we found that the p21-activated kinase homologue Ste20 is also important for both apical growth and bipolar bud site selection. We further examined how the duration of polarized growth affects bipolar bud site selection by using mutations in cell cycle regulators that control the timing of growth phases. The grr1Delta mutation enhances apical growth by stabilizing G(1) cyclins and increases the distal-pole budding in diploids. Prolonging polarized growth phases by disrupting the G(2)/M cyclin gene CLB2 enhances the accuracy of bud site selection in wild-type, spa2Delta, and ste20Delta cells, whereas shortening the polarized growth phases by deleting SWE1 decreases the fidelity of bipolar budding. This study reports the identification of components required for apical growth and demonstrates the critical role of polarized growth in bipolar bud site selection. We propose that apical growth and repolarization at the site of cytokinesis are crucial for establishing spatial cues used by diploid yeast cells to position division planes.

Retinoic acid syndrome induced by arsenic trioxide in treating recurrent all-trans retinoic acid resistant acute promyelocytic leukemia.

Arsenic Trioxide (As2O3) is an effective agent for treating acute promyelocytic leukemia achieving a complete remission rate of about 60% to 90%. It is similar to all-trans retinoic acid (ATRA) when treating acute promyelocytic leukemia (APL), because both agents have limited side effects compared to conventional chemotherapy, although the treatment period is more prolonged. During treatment, both agents may induce leukocytosis, and in patients taking ATRA, leukocytosis appears to be related to the development of retinoic acid syndrome (RAS). We report here a case of APL treated with ATRA in combination with chemotherapy 3 years earlier. During treatment, an episode of RAS with fever, edema, pericardiac effusion etc. was encountered. Recently, she had a relapse of leukemia, and As2O3 therapy was used. Leukocytosis developed again, and symptoms of fever, skin rash, edema resembling a RAS also developed, which was quickly relieved by steroid administration in a manner resembling response to RAS.