Reaction of cytochrome P450 with cumene hydroperoxide: ESR spin-trapping evidence for the homolytic scission of the peroxide O-O bond by ferric cytochrome P450 1A2

ESR spin trapping was used to investigate the reaction of rabbit cytochrome P450 (P450) 1A2 with cumene hydroperoxide. Cumene hydroperoxide-derived peroxyl, alkoxyl, and carbon-centered radicals were formed and trapped during the reaction. The relative contributions of each radical adduct to the composite ESR spectrum were influenced by the concentration of the spin trap. Computer simulation of the experimental data obtained at various 5,5-dimethyl-1-pyrroline N-oxide (DMPO) concentrations was used to quantitate the contributions of each radical adduct to the composite ESR spectrum. The alkoxyl radical was the initial radical produced during the reaction. Experiments with 2-methyl-2-nitrosopropane identified the carbon-centered adducts as those of the methyl radical, hydroxymethyl radical, and a secondary carbon-centered radical. The reaction did not require NADPH-cytochrome P450 reductase or NADPH. It is concluded that the reaction involves the initial homolytic scission of the peroxide O-O bond to produce the cumoxyl radical. Methyl radicals were produced from the beta-scission of the cumoxyl radical. The peroxyl adduct was not observed in the absence of molecular oxygen. We conclude that the DMPO peroxyl radical adduct detected in the presence of oxygen was due to the methylperoxyl radical formed by the reaction of the methyl radical with oxygen. At a higher P450 concentration, a protein-derived radical adduct was also detected.     

One or two incisions for nephroureterectomy in transitional cell renal pelvis tumours

A retrospective study comprising 18 patients with transitional cell renal pelvis tumours (TCPT) was carried out to evaluate the results after two different surgical procedures for nephroureterectomy. The kidney was removed by a flank incision and the lower part of the ureter by either an incision in the lower part of the abdomen or intussusception of the ureter followed by transurethral resection of the ureteral orifice. Eight patients were subjected to nephroureterectomy by means of two incisions and another eight patients underwent a simple nephrectomy followed by ureteral intus-susception and transurethral resection. Two patients received other treatments. After nephroureterectomy with a separate incision for ureterectomy, the average hospital stay was 12 days, compared with 7.5 days in patients operated upon with only one abdominal incision. Recurrence of tumour or survival was not significantly different in the two groups.     

Experimental Study of Ice Jam Thickening under Dynamic Flow Conditions

River ice jams are a common occurrence on northern rivers, and their formation can present a severe flood risk to nearby communities. As more and more river regulation projects are developed to provide an alternative to fossil fuels for electrical power-generating capacity, our need to understand the mechanisms associated with ice jam formation under variable flow conditions becomes more vital. This is because, at present, hydropeaking operations are often severely curtailed during the ice-affected seasons due to concerns that sudden flow fluctuations might instigate ice jams and associated flooding. Here, an experimental investigation explores the effects of rapid increases in discharge on ice jam formation and evolution. It is found that the thickness of ice jams formed under highly dynamic flow conditions tend to be slightly thinner than those formed during steady carrier flows for comparable discharges. Also, despite the highly dynamic nature of these consolidation events, the resulting ice thicknesses appear reasonably well approximated by steady flow theory.     

The transjugular stent implantation for the treatment of malignant portal and hepatic vein obstruction in cancer patients

BACKGROUND: The increase in portal vascular resistance is a significant complication of metastatic disease to the liver or locally advanced cancer, e.g., biliary cancer. PATIENTS AND METHODS: This paper describes the successful palliative treatment of two cancer patients with portal hypertension presenting with the symptoms of tense ascites, mesenteric congestion, and severe variceal bleeding. By creating a stenttract between a hepatic vein and a main branch of the portal vein and/or by placing an extendable stent into the portal vein, the transjugular intrahepatic portosystemic stent-shunt (TIPS) technique was used to decompress the portovascular system. RESULTS: The TIPS-technique offers a new, safe and effective palliation for malignant portal hypertension. In both patients, the symptoms of the portal hypertension disappeared after the procedure. This was accompanied by a significant improvement of the patients performance status allowing an early ambulation. CONCLUSION: Our findings demonstrate the feasibility and effectiveness of the TIPS procedure as a minimal invasive treatment for portal vein decompression in selected tumor patients.     

Acquiring rule sets as a product of learning in a logical neuralarchitecture

Envisioning neural networks as systems that learn rules calls forth the verification issues already being studied in knowledge-based systems engineering, and complicates these with neural-network concepts such as nonlinear dynamics and distributed memories. We show that the issues can be clarified and the learned rules visualized symbolically by formalizing the semantics of rule-learning in the mathematical language of two-valued predicate logic. We further show that this can, at least in some cases, be done with a fairly simple logical model. We illustrate this with a combination of two example neural-network architectures, LAPART, designed to learn rules as logical inferences from binary data patterns, and the stack interval network, which converts real-valued data into binary patterns that preserve the semantics of the ordering of real values. We discuss the significance of the formal model in facilitating the analysis of the underlying logic of rule-learning and numerical data representation. We provide examples to illustrate the formal model, with the combined stack interval/LAPART networks extracting rules from numerical data.     

Global analysis of the thermal and chemical denaturation of the N-terminal domain of the ribosomal protein L9 in H2O and D2O. Determination of the thermodynamic parameters, deltaH(o), deltaS(o), and deltaC(o)p and evaluation of solvent isotope effects

The stability of the N-terminal domain of the ribosomal protein L9, NTL9, from Bacillus stearothermophilus has been monitored by circular dichroism at various temperatures and chemical denaturant concentrations in H2O and D2O. The basic thermodynamic parameters for the unfolding reaction, deltaH(o), deltaS(o), and deltaC(o)p, were determined by global analysis of temperature and denaturant effects on stability. The data were well fit by a model that assumes stability varies linearly with denaturant concentration and that uses the Gibbs-Helmholtz equation to model changes in stability with temperature. The results obtained from the global analysis are consistent with information obtained from individual thermal and chemical denaturations. NTL9 has a maximum stability of 3.78 +/- 0.25 kcal mol(-1) at 14 degrees C. DeltaH(o)(25 degrees C) for protein unfolding equals 9.9 +/- 0.7 kcal mol(-1) and TdeltaS(o)++(25 degrees C) equals 6.2 +/- 0.6 kcal mol(-1). DeltaC(o)p equals 0.53 +/- 0.06 kcal mol(-1) deg(-1). There is a small increase in stability when D2O is substituted for H2O. Based on the results from global analysis, NTL9 is 1.06 +/- 0.60 kcal mol(-1) more stable in D2O at 25 degrees C and Tm is increased by 5.8 +/- 3.6 degrees C in D2O. Based on the results from individual denaturation experiments, NTL9 is 0.68 +/- 0.68 kcal mol(-1) more stable in D2O at 25 degrees C and Tm is increased by 3.5 +/- 2.1 degrees C in D2O. Within experimental error there are no changes in deltaH(o) (25 degrees C) when D2O is substituted for H2O.     

Surgical release for intubation purposes in postburn contractures of the neck

One hundred and twenty-four patients over the age of 75 years were assessed for the cause of their macrocytosis (MCV > 95 fl). A definitive diagnosis was reached in 75/124 (60%) by non-invasive techniques. The remainder underwent a bone marrow biopsy yielding a definitive diagnosis in a further six patients who had an identifiable myelodysplastic syndrome (MDS). A high proportion of the remainder had morphological abnormalities which fitted with no recognized pathological entity. It is suggested that these may represent MDS in evolution.