Characterization of the monocyte-specific esterase (MSE) gene

Carboxylic esterases are widely distributed in hematopoietic cells. Monocytes express the esterase isoenzyme (termed 'monocyte-specific esterase', MSE) that can be inhibited by NaF in the alpha-naphthyl acetate cytochemical staining. We examined the expression of MSE in normal cells and primary and cultured leukemia-lymphoma cells. The MSE protein was demonstrated by isoelectric focusing (IEF); MSE mRNA expression was investigated by Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). The following samples were positive for MSE protein and Northern mRNA expression: 20/24 monocytic, 4/32 myeloid, and 1/20 erythroid-megakaryocytic leukemia cell lines, but none of the 112 lymphoid leukemia or lymphoma cell lines; of the normal purified cell populations only the monocytes were positive whereas, T, B cells, and granulocytes were negative; of primary acute (myelo) monocytic leukemia cells (CD14-positive, FAB M4/M5 morphology) 14/20 were Northern mRNA and 11/14 IEF protein positive. RT-PCR revealed MSE expression in 29/49 Northern-negative lymphoid leukemia-lymphoma cell lines. The RT-PCR signals in monocytic cell lines were on average 50-fold stronger than the mostly weak trace expression in lymphoid specimens. On treatment with various biomodulators, only all-trans retinoic acid significantly upregulated MSE message and protein levels but could not induce new MSE expression in several leukemia cell lines; lipopolysaccharide and interferon-gamma increased MSE expression in normal monocytes. Analysis of DNA methylation with sensitive restriction enzymes showed no apparent regulation of gene expression by differential methylation; the MSE gene is evolutionarily conserved among mammalian species; the half-life of the human MSE transcripts was about 5-6 h. The extent of MSE expression varied greatly among different monocytic leukemia samples. However, the MSE overexpression in a significant number of specimens was not associated with gene amplification, gross structural rearrangements or point mutations within the cDNA region. Taken together, the results suggest that MSE expression is not absolutely specific for, but strongly associated with cells of the monocytic lineage; MSE is either not expressed at all or expressed at much lower levels in cells from other lineages. The biological significance, if any, of rare MSE messages in lymphoid cells detectable only by the hypersensitive RT-PCR remains unclear. Further studies on the regulation of this gene and on the physiological function of the enzyme will no doubt be informative with respect to its striking overexpression in some malignant cells and to a possible role in the pathobiology of monocytic leukemias

Impact of Routine Platelet Reactivity Testing with VerifyNow Assay on Antiplatelet Choice After Percutaneous Coronary Intervention

Background: High on-treatment ADP platelet reactivity (HPR) measured by VerifyNow P2Y12 assay (VN) is an established risk factor for ischemic events after percutaneous coronary intervention (PCI). We hypothesized that routine use of VN at time of PCI in clinical practice may affect choice of P2Y12 antiplatelet therapy at discharge. Methods: In a single center retrospective analysis, we examined the influence of VN testing on choice of P2Y12 inhibitor post PCI in routine clinical practice. Assessment of HPR was used routinely in clinical care during the time period of analysis at discretion of clinical providers. Subjects with PRU>208 after the loading dose of clopidogrel or during clopidogrel steady state were switched to alternate P2Y12 inhibitors. Results: We identified 1001 patients with PCI during the time period specified. A total of 252 subjects underwent VN testing. Among those, 43% were found to have HPR on clopidogrel and were switched to alternate therapies (prasugrel [n=60], ticagrelor [n=48]). Patients who had VN platelet function testing were more likely to be discharged on clopidogrel as compared to those who did not have VN assay done (57% vs. 50%, p=0.039). There was no significant difference in 1-year net-MACE (CVD, MI, stent thrombosis, BARC 2 or higher bleeding) using tailored antiplatelet therapy (VN testing) as compared to standard of care group (adjusted HR:0.92, 95% CI: 0.54-1.5, p=0.74). Conclusion: Routine use of VN assay in personalized antiplatelet treatment decision-making after PCI is associated with lower likelihood of using novel P2Y12 inhibitors

Механические испытания элементов космической техники на синусоидальные воздействия

Целью работы является определение собственных частот трехмерной модели двигателя-маховика системы ориентации малого космического аппарата, а также ее поведение под действием квазистатической нагрузки, синусоидальных и случайных вибраций, акустического и ударного воздействия. Компьютерный анализ, проведенный в процессе проектирования, позволяет определить характеристики изделия и провести оптимизацию конструкции без создания опытного образца. Анализ проводился с помощью специального программного обеспечения "T-Flex Анализ". Исходная трехмерная модель была разбита на три подсборки: корпусную, роторную и статорную. Приведены результаты частотного анализа и расчета при воздействии на двигатель-маховик квазистатических нагрузок. По результатам проведенного компьютерного конечно-элементного анализа можно сказать, что спроектированный двигатель-маховик с большим запасом удовлетворяет требованиям надежности. Большие коэффициенты запасов говорят о том, что конструкцию в дальнейшем можно оптимизировать

Tyrosyl-DNA phosphodiesterase 1 (TDP1) and its natural mutant scan1 inhibitors development as prototypes of drugs

In the present study, we performed screening of 21 compounds - derivatives of coumarin as inhibitors of tyrosyl-DNA phosphodiesterase 1 (Tdp1) and its mutant SCAN1. The ability of these compounds to inhibit Tdp1, important target for anti-cancer therapy, was studied. The most active derivatives have IC50 value of 0,1-1 mkM. SCAN1 inhibitors were found first in the world. They can likely underlie the development of drugs preventing or slowing the progressive cerebellar atrophy to improve quality of life of SCAN patients

Seasonal variations of glaciochemical, isotopic and stratigraphic properties in Siple Dome (Antarctica) surface snow

Six snow-pit records recovered from Siple Dome, West Antarctica, during 1994 are used to study seasonal variations in chemical (major ion and H202), isotopic (deuterium) and physical stratigraphic properties during the 1988-94 period. Comparison of δD measurements and satellite-derived brightness temperature for the Siple Dome area suggests that most seasonal SD maxima occur within ±4 weeks of each 1 January. Several other chemical species (H2O2, non-sea-salt (nss) SO4 2-, methanesulfonic acid and NO3-) show coeval peaks with SD, together providing an accurate method for identifying summer accumulation. Sea-salt-derived species generally peak during winter/spring, but episodic input is noted throughout some years. No reliable seasonal signal is identified in species with continental sources (nssCa2+ nss Mg2+), NH4 + or nssCl-. Visible strata such as large depth-hoar layers (\u3e5 cm) are associated with summer accumulation and its metamorphosis, but smaller hoar layers and crusts are more difficult to interpret. A multi-parameter approach is found to provide the most accurate dating of these snow-pit records, and is used to determine annual layer thicknesses at each site Significant spatial accumulation variability exists on an annual basis, but mean accumulation in the sampled 10 km2 grid for the 1988-94 period is fairly uniform

Применение треугольной схемы расположения скважин для добычи урана из малого изометрического рудного тела

The dynamical behaviour of the laser beam fusion cutting process of metals is investigated. Integral methods such as the variational formulation are applied to the partial differential equations for the free boundary problem and a finite dimensional approximation of the dynamical system is obtained. The model describes the shape of the evolving cutting kerf and the melt flow. The analysis is aimed at revealing the characteristic features of the resultant cut, for example, ripple formation and adherent dross. The formation of the ripples in the upper part of the put, where no resolidified material is detectable, is discussed in detail. A comparison with numerical simulations and experiments is made

Анализ переноса тепла в активном элементе электромагнита

Описан приближенный способ определения тепловых потерь в плоском активном элементе конечных размеров при симметричных условиях охлаждения. Характеристика тепловых потерь определяется числом Био. Проведено исследование нестационарного теплового состояния в шихтованном пакете магнитопровода с равномерно распределенными источниками тепла на основе конечно-разностного метода. Приведены результаты численного моделирования процесса нестационарной двумерной теплопроводности, протекающего в поперечном сечении активного элемента электромагнита