Mechanisms of resistance in a human cell line exposed to sequential topoisomerase poisoning

Camptothecins are a new class of anticancer drugs that target DNA topoisomerase I; current efforts are directed toward elucidating optimal combinations of these drugs with other antineoplastic agents. A rationale for the use of sequential therapy involving the combination of camptothecins with topoisomerase II-targeting drugs, such as etoposide, has arisen from observations of increased topoisomerase II protein levels in cell lines resistant to camptothecin. In an effort to understand potential mechanisms of resistance to this strategy, we developed a U-937 cell subline, denoted RERC, that is capable of surviving exposure to sequential topoisomerase poisoning. The RERC cells are 200-fold resistant to camptothecin, 8-fold resistant to etoposide, and 10-fold hypersensitive to cisplatin compared to the parental U-937 cells. Biochemical analyses indicate that the resistant phenotype involves alterations in both topoisomerase I and topoisomerase IIalpha. Topoisomerase I catalytic activity in the resistant cells is similar to that of the parental line but is resistant to camptothecin. Moreover, the resistant cells express a single mRNA species of topoisomerase I that codes for a mutation in codon 533. In addition, topoisomerase IIalpha protein levels are decreased 10-fold in the resistant line, coincident with a two-fold decrease in the expression of topoisomerase IIalpha mRNA. Collectively, these results indicate that resistance to sequential topoisomerase poisoning may involve a reduction in total cellular topoisomerase activity.     

Fine needle aspiration cytodiagnosis of subcutaneous fat necrosis of newborn. A case report

We recently diagnosed subcutaneous fat necrosis in a newborn female infant using fine needle aspiration cytology. The neonate had perinatal asphyxia and her mother a difficult labor, but otherwise the neonate was well developed and healthy and within a few days developed well-defined areas of subcutaneous induration all over. On cytologic examination of the aspirated material, many necrotizing fat cells were found with refractile, needle-shaped crystals arranged in a sheaflike or starburst pattern. Subcutaneous fat necrosis of the newborn is uncommon today, and although the histologic findings from excised tissue are known, this appears to be the first case in which the diagnosis was possible from a sample of fine needle aspirate.     

Quantitation of Sulfacetamide, Sulfadiazine, Sulfamerazine and Sulfame Thazine in Various Cominations Dsing High-Performance Liquid Chromatography

A reverse phase high-performance liquid chromatography method for the quantitation of sulfacetamide, sulfadiazine, sulfamerazine, and sulfamethazine in various combinations has been developed. The method is simple, accurate, precise and reproducible. The percent relative standard deviations based on 6 injections were 2.1, 0.6, 1.9, and 1.6 for sulfacetamide, sulfadiazine, sulfamerazine, and sulfamethazine, respectively. The ratio of peak heights (drug/internal standard) wer closely related (r value 0.99 or better) to concentrations (± 20% of the standard solution concentrations). The results of synthetic mixtures showed quantitative recovery and method was successfully applied to commercial dosage forms (tablets and suspension). Extraction of sulfa drugs from the dosage forms required a very simple procedure.     

Nickel and chromium cycles: Stocks and flows project part IV

Nickel and chromium are essential ingredients in alloys increasingly important for energy-efficient, environmentally friendly modern technology. Quantitative assessment of the flows of these metals through the world economy from resource extraction to final disposal informs resource policy, energy planning, environmental science, and waste management. This article summarizes the worldwide technological cycles of nickel and chromium in 2000. Stainless steel is the major use of these metals, but they serve numerous other special needs, as in superalloys for high-temperature service, as plating materials, and in coinage. Because they are used primarily in alloys, novel recycling issues arise as their use becomes more widespread. “... the great New York and St. Louis double track, nickel plated railroad...” — Norwalk, Ohio, Chronicle 10 March 1881 announces arrival of surveyors for the future Nickel Plate Railway “Later [1911] I formed an alloy of Iron and Chromium, which showed remarkable resistance to rust and tarnish ... [It was] rediscovered by an Englishman named Brearley, in 1914.” —Elwood Haynes to Stephen F. Roberts, 17 January 1925     

Influence of the silicon surface treatment by plasma etching and scratching on the nucleation of diamond grown in HFCVD - a comparative study

A comparative study for the nucleation of diamond was carried out using surface treatment like (i) surface scratching with 1 μm diamond paste and (ii) surface etching using chlorine plasma at different RF powers (50, 100 and 150 W). Atomic force microscopic study shows variation in roughness from 31 nm to 110 nm. Scratching results in random scratches, whereas plasma etches a surface uniformly. Scanning electron microscopic observations show well faceted crystallites with a predominance of angular shaped grains corresponding to 〈100〉 and 〈110〉 crystallite surfaces for the scratched as well as plasma etched substrate. Surface etching at 150 W plasma power results in a better growth in comparison with 50 and 100 W plasma powers. Chlorine-radical is found responsible for the changes in the growth morphology. Raman spectroscopy shows a sharp peak at 1,332 cm⁻¹ and a peak at ∼1,580 cm⁻¹ for both samples.     

Effects of partial recrystallization on high-cycle fatigue deformation and crack generation of a nitrogen-strengthened 32Mn-7Cr austenitic steel at liquid-nitrogen temperature

To achieve higher fatigue resistance against subsurface crack generation, both the refinement of grain structure and the introduction of mobile dislocations on various slip systems have been shown to be effective in the 32Mn-7Cr austenitic steel. A novel treatment which consisted of cold grooved rolling and partial recrystallization was introduced to modify the microstructure. High-cycle fatigue properties and fatigue-crack generation were investigated for both the solution-treated (ST) and the partially recrystallized (PR) materials at 77 K. The PR material displayed higher fatigue strength than the ST material, especially in the high-cycle regime. No subsurface crack generation was detected for the PR material; however, it appeared in the lower peak stress and/or in the longer-life range for the ST material. Intergranular facets formed a subsurface crack initiation site in the ST material. Since the dislocation structure that developed in the fatigued PR material assisted homogeneous and multidirectional plastic deformation, the localized deformation and/or the stress concentration at the grain boundaries by coplanar arrays were believed to be relieved. Therefore, intergranular cracking due to incompatibility at a grain boundary may disappear.