In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Action semantics-directed prototyping

We present a methodology for compiler synthesis based on Mosses-Watt's action semantics. Each action in action semantics notation is assigned specific “analysis functions”, such as a typing function and a binding-time function. When a language is given an action semantics, the typing and binding-time functions for the individual actions compose into typing and binding-time analyses for the language; these are implemented as the type checker and static semantics processor, respectively, in the synthesized compiler. Other analyses can be similarly formalized and implemented. We show a sample language semantics and its synthesized compiler, and we describe the compiler synthesizer that we have developed.     

Processing to optimize the strength of heavily drawn Cu-Nb alloys

Heavily drawn Cu-Nb alloys display quite high ultimate tensile strengths. A modification to the consumable arc-casting technique used to prepare these alloys is shown to decrease the as-cast niobium dendrite diameter,t ₀, and also increase strength. Evaluation of strength, niobium filament spacing and thickness data show that strength varies with as-cast niobium dendrite size as somewhere betweent _o ^–0.36 tot _o ^–0.50 . Splat-cooling techniques demonstrate that minimum niobium dendrite sizes as small as 0.22m are possible. These sizes are over a factor of 10 smaller than has been achieved by consumable arc casting, and it is therefore suggested that processing rapidly solidified powders of Cu-Nb alloys should have significant advantages for preparing high-strength heavily drawn Cu-Nb alloys.     

Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.     

Sulfur in chromia

The solubility of sulfur in chromia has been studied in H₂-H₂O-H₂S tagged with³⁵S at 973 and 1173 K at low oxygen and sulfur partial pressures typical for coal gasification-systems. For monocrystalline samples, it has been shown that sulfur-containing species are only present adsorbed on the surface of the specimens and can be removed by ultrasonic cleaning in acetone. The surface coverage after 4 weeks of exposure to H₂-H₂O-H₂S was between 2.8 and 19.3% of a monolayer. In polycrystalline chromia, sulfur was located only in pores and cracks of the sample. In dense, compact areas of the specimens the solubility of sulfur was below the detection limit of autoradiography, which was estimated to be better than 0.17 ppm.     

Silicon Nitride Derived from an Organometallic Polymeric Precursor: Preparation and Characterization

Partially crystalline Si₃N₄, with nanosized crystals and a specific surface area greater than 200 m²/g, is obtained by pyrolysis of a commercially available vinylic polysilane in a stream of anhydrous NH₃ to 1000°C. This polymer does not contain N initially. Crystallization to high-purity α-Si₃N₄ proceeds with additional heating above 1400°C under N₂. The changes in crystallinity, powder morphology, infrared spectra, and elemental compositions, for samples annealed from 1000° to 1600°C under N₂, are consistent with an amorphous-to-crystalline transformation. Although macroscopic consolidation and local densification occur at 1400°C, volatilization and accompanying weight loss limit bulk densification. The effect of temperature on specific surface area is examined and related to the sintering process. These results are applicable to pyrolysis, decomposition, and crystallization studies of ceramics synthesized by polymeric precursor routes.