No abstract available.
Carboxylesterase* ; Leukemia, Promyelocytic, Acute*

According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.
Carboxylesterase/metabolism* ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions

We report a case of microgranular variant of acute promyelocytic leukemia with strong positivity in nonspecific esterase stain (inhibited by sodium fluoride) in a 21-onth-ld girl who had complained of intermittent fever and severe vomiting. At admission, she showed marked leukocytosis in the peripheral blood. The majority of leukocytes were immature cells which exhibited marked nuclear irregularity and had sparse dust-ike granules in their cytoplasm. In immunophenotyping, these cells showed CD13 and CD33 positivity and in cytogenetic study, they showed t(15;17) abnormality. The patient died at the 6th hospital day because of pulmonary and intracranial hemorrhage.
Carboxylesterase* ; Cytogenetics ; Cytoplasm ; Female ; Fever ; Humans ; Immunophenotyping ; Intracranial Hemorrhages ; Leukemia, Promyelocytic, Acute* ; Leukocytes ; Leukocytosis ; Sodium ; Vomiting

We report a case of microgranular variant of acute promyelocytic leukemia with strong positivity in nonspecific esterase stain (inhibited by sodium fluoride) in a 21-onth-ld girl who had complained of intermittent fever and severe vomiting. At admission, she showed marked leukocytosis in the peripheral blood. The majority of leukocytes were immature cells which exhibited marked nuclear irregularity and had sparse dust-ike granules in their cytoplasm. In immunophenotyping, these cells showed CD13 and CD33 positivity and in cytogenetic study, they showed t(15;17) abnormality. The patient died at the 6th hospital day because of pulmonary and intracranial hemorrhage.
Carboxylesterase* ; Cytogenetics ; Cytoplasm ; Female ; Fever ; Humans ; Immunophenotyping ; Intracranial Hemorrhages ; Leukemia, Promyelocytic, Acute* ; Leukocytes ; Leukocytosis ; Sodium ; Vomiting

BACKGROUND: Although immunophenotyping of leukemias has improved diagnostic accuracy and reproducibility, it has also caused diagnostic confusion regarding the lineage of leukemic cells. So far, lots of papers about acute leukemias with coexpression of another lineage markers with different technical methodologies and different criteria have been published in Korea and other countries. The authors investigated the frequency and immunophenotypic characteristics of the leukemias with aberrant lineage markers from data obtained at Korea University Hospital by a retrospective study. METHODS: From Jan. 1993 to Feb. 1996, 179 leukemias had been requested for immunophenotypig and 28 cases among them with unusual immunophenotypes were retrieved according to their immunophenotyping results. For the final diagnosis all the slides stained with Wright-Giemsa, peroxidase, Periodic-Acid Schiff, Sudan black B, and nonspecific esterase were re-examined, and all the flow cytometric results were reanalyzed. RESULTS: Among 28 cases, 3 cases(10%) were acute biphenotypic leukemias(BP) one with B lymphoid and myeloid markers and the other two with T lymphoid and myeloid markers. One case of intralineage bilinear acute leukemia(ILBL) with two separate populations of megakaryocytic cells and monocytic cells was noted. 6 cases(21%) were acute myeloblastic leukemias expressing lymphoid associated markers(Ly+AMLs; CD19) and 8 cases(28%) were myeloid antigen-positive acute lymphoblastic leukemias(My+ALLs, four with CD13+ and three with CD33+ and one with blastic transformation of chronic myelogeneous leukemia). Because of the change in diagnostic criteria, lymphocyte contamination, or low setting of negative control, 10 cases (36%) were not included to be of unusual immunophenotypes. CONCLUSIONS: Frequency of acute hybrid leukemia was 2.2 % of all leukemias. Ly+AMLs was 3.4%, and My+ALL was 4.4%. In conclusion, first, quality control of the flow cytometry and careful interpretation especially in terms of positive cut-off value and gating, are needed. Secondly, national guidelines for the criteria of the hybrid leukemia and My+ALLs and Ly+AMLs are necessary for the elucidation of the prognostic implication of those leukemias.
Carboxylesterase ; Diagnosis ; Flow Cytometry ; Immunophenotyping ; Korea ; Leukemia* ; Leukemia, Myeloid, Acute ; Lymphocytes ; Peroxidase ; Quality Control ; Retrospective Studies ; Sudan

Human carboxylesterase 1 (CES1) is a serine esterase that hydrolyzes various exogenous compounds. Single nucleotide polymorphisms (SNPs) of CES1 may lead to inter-individual metabolic variability of its substrates. The allele and haplotype frequencies of known SNPs have been demonstrated to vary among ethnic groups. We analyzed genetic variations of CES1 in a Korean population. Direct sequencing of all exons and flanking regions of the CES1 gene was performed on samples obtained from 200 Koreans. We identified 41 SNPs. The most frequent SNPs was -914G>C (frequency: 99.5%), followed by 4256G>A (frequency: 65.8%), -75T>G (frequency: 59.3%). Haplotype analysis using the identified SNPs revealed fifteen haplotypes (> or =1% haplotype frequency) in our samples. The most frequent haplotype was Hap1 (frequency: 15.4%). Among the identified 41 SNPs, nine of which are novel variants and 14 SNPs were nonsynonymous variants. Using the functional predictive software PolyPhen-2, the G19V, E221G, and A270S variants were predicted to be most likely damaging to the function and structure of CES1. In-vitro analyses for two of these variants have been previously performed; however, functional evaluation of E221G (11657A>G, rs200707504) still needs to be conducted. Therefore, further studies are warranted to characterize the functional impact of E221G on CES1 activity.
Alleles ; Asian Continental Ancestry Group ; Carboxylesterase* ; Ethnic Groups ; Exons ; Genetic Variation ; Haplotypes ; Humans ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; Serine

Myeloid sarcoma is a rare extramedullary myeloid tumor, which is frequently misdiagnosed when no evidence of leukemia is initially observed. Here, we report on a peculiar case of a 49-year-old man afflicted with multiple masses in the jejunum, the superior mesentery, and the serosa of the transverse colon, without leukemic manifestation. The tumor was composed of undifferentiated small round cells containing eosinophilic cytoplasm, which were negative for myeloperoxidase, nonspecific esterase, lysozyme, terminal deoxynucleotidyl transferase, leukocyte common antigen, CD3, CD4, CD15, CD20, CD30, CD43, CD56, CD68/PG-M1, CD79a, human melanoma black-45, c-kit, and CD34 with positivity only for CD68/KP1, CD99, and vimentin. Under electron microscopy, those cells had abundant membrane-bound cytoplasmic granules that measured 200 to 300 nm in diameter, which were consistent with granulocytic azurophilic granules. The tumor was finally diagnosed as a myeloid sarcoma. The presence of non-leukemic myeloid sarcomas showing immunonegativity for conventional myeloid-leukemic markers necessitated a diagnosis by ultrastructural observation.
Antigens, CD45 ; Carboxylesterase ; Colon, Transverse ; Cytoplasm ; Cytoplasmic Granules ; DNA Nucleotidylexotransferase ; Eosinophils ; Humans ; Intestinal Obstruction ; Jejunum ; Leukemia ; Melanoma ; Mesentery ; Microscopy, Electron ; Muramidase ; Peroxidase ; Sarcoma, Myeloid ; Serous Membrane ; Vimentin

This experiment was designed for the evaluation of the usefulness of enzyme histochemistry in the determination of the lapse of time in brain wound, and also for the establishment of medicolegal 'biological time table' on brain wound. Brain injury was made by contusion and laceration of meninges and brain itself in rats. The results were as follows; 1) By routine histological technique, estimation of the lapse of time in brain wound could be possible 4 hours after the infliction of wound. 2) The earliest change of enzyme activities was recognizable by the decreased activities of ATPase and succinic dehydrogenase 30 minutes after the injury. These decreased enzyme activities were not recovered up to the 4th day after the brain injury. 3) Increased acid phosphatase activity was noticed 1 hour, and beta-glucuronidase, 2 hours after the injury in a mild degree. Both increased activities were pronounced following the lapse of time in brain wound. 4) No significant change was seen in alkaline phosphatase, monoamine oxidase, non-specific esterase and leucine aminopeptidase activities throughout the experimental period up to the 4th day. So the enzyme histochemistry of these enzymes seemed to be little valuable for the study on the timing of wound in brain injury. In the light of these results it appeared that the enzyme histochemistry, in particular of ATPase, succinic dehydrogenase, and acid phosphatase, for the estimation of timing of brain wound not only shortened the histological "lag period" up to 30 minutes after the injury, but also provided a useful information in determining the biological time table following the brain injury.
Acid Phosphatase ; Adenosine Triphosphatases ; Alkaline Phosphatase ; Animals ; Brain Injuries* ; Brain* ; Carboxylesterase ; Contusions ; Glucuronidase ; Histological Techniques ; Lacerations ; Leucyl Aminopeptidase ; Meninges ; Monoamine Oxidase ; Rats ; Succinate Dehydrogenase ; Wounds and Injuries

AIMTo study the stereoselectivity of skin carboxylesterase metabolism and its molecular biological foundation for improving drug percutaneous absorption.

METHODSKetoprofen ethyl ester was used as a model drug, and skin homogenate was applied for studying the stereoselectivity of carboxylesterase metabolism. Human liver L02 cell was used as control of carboxylesterase expression, and RT-PCR was used for studying the expression of carboxylesterase.

RESULTSThe main metabolite of ketoprofen ethyl ester in human skin homogenate was R-ketoprofen. Human carboxylesterase-2 was highly expressed in skin and its cells. However, the expression of human carboxylesterase-1 was very weak or not detectable.

CONCLUSIONHuman carboxylesterase-2 is the main hydrolytic enzyme of prodrugs in percutaneous absorption, and shows metabolic stereoselectivity to prodrugs with chiral esters.

Adult ; Carboxylesterase ; genetics ; metabolism ; Cell Line ; Cells, Cultured ; Humans ; Ketoprofen ; metabolism ; Liver ; cytology ; enzymology ; Prodrugs ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Skin ; enzymology ; Stereoisomerism

OBJECTIVETo examine a) the effect of organophosphorus pesticide exposure on activity of carboxylic esterases, namely butyrylcholinesterase (BChE), carboxylesterase (CarbE) and paraoxonase (PonE); and b) the association of polymorphisms of BChE and PonE with individual genetic susceptibility to organophosphorus pesticide exposure.

METHODSA cross-sectional study was conducted in 75 workers exposed to organophosphorus pesticides and 100 non-exposed controls. The serum activity of these enzymes was measured. Variant forms of BCHE-K, PON-192, and PON-55 were detected. A symptom score was developed as a proxy measure of clinical outcomes.

RESULTSActivities of both BChE and CarbE were lower in exposed workers (27.3+/-21.65 nmolxh(-1)xmL(-1) and 235.6+/-104.03 nmolxmin(-1)xmL(-1)) than in non-exposed workers (78.313+/-30.354 nmolxh(-1)xmL(-1) and 362.681+/-194.997 nmolxmin(-1)xmL(-1)). The activity of PonE was not associated with exposure status. The AChE activity in the exposed workers with BCHE-K genotype UU (61 cases), genotype UK (12 cases) and genotype KK (2 cases) was 105.05, 84.42 and 79.00 mmolxh(-1)xmL(-1), respectively and the accumulative symptom scores were 3.74, 9.17, and 12.50 accordingly. The AChE activity in the exposed workers with PON-192 genotypeBB (37), genotype AB (27) and genotype AA (11) was 116.8, 91.2, and 72.3 mmolxh(-1)xmL(-1), respectively and the symptom scores were 2.00, 6.74, and 9.73 accordingly. The AChE activity in those with PON-55 genotype LL (70) and genotype LM (5) was 102.4 and 82.8 mmolxh(-1)xmL(-1) and the symptom scores were 4.53 and 9.20. The symptom score was the highest in individuals with abnormal homozygote for each of the three gene loci.

CONCLUSIONSLong-term exposure to organophosphorus pesticides can inhibit BChE and CarbE activity, but exerts no inhibitory effect on PonE activity. Different genotypes of BCHE-K, PON-192, and PON-55 may be related to the severity of adverse health effects of organophosphorus pesticide exposure. Implications of potentially higher susceptibility of workers with mutant homozygotes should be evaluated to reduce health risks.

Adult ; Base Sequence ; Butyrylcholinesterase ; drug effects ; Carboxylesterase ; antagonists & inhibitors ; DNA Primers ; Environmental Exposure ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Organophosphorus Compounds ; toxicity ; Pesticides ; toxicity ; Polymerase Chain Reaction