A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Sympathetic blockade of isolated rat hindlimbs by intra-arterial guanethidine: the effect on blood flow and arterial-venous shunting

In order to improve the understanding of the role of sympathetic nerve degeneration in reimplantation failure, the hindlimbs of eight rats (Group I) underwent near-complete amputation. The soft tissues of the hindlimb were transected at the proximal thigh with the femoral artery, vein and femur left intact. The femoral vessels were clamped and guanethidine was infused into a branch of the femoral artery of the right leg of each animal, while saline was injected into the left leg. The clamps were removed after 15 minutes. A baseline preoperative injection of radiolabeled microspheres was made, and subsequent injections at 6, 12, 18, and 24 hours postoperation. Twelve rats (Group II) were then used to assess the amount of arterial-venous shunting preoperatively (n = 6) and at 18 hours postoperation (n = 6), by venous sampling. Blood flow to both limbs increased postoperation, but there was significantly more flow in the guanethidine treated limb at 18 and 24 hours postoperation. The amount of shunting was approximately 50% in both limbs at 18 hours, as compared to 10% preoperation. These results highlight the potential benefit of guanethidine and other sympathetic blocking agents in reimplantation to increase blood flow, decrease tissue ischemia and increase anastomotic patency rates. They also suggest that sympathetic nerve degeneration did not affect the volume of arterial-venous shunting in this model, but the difference in blood flow was likely due to arteriolar vasospasm. Further study is needed to elucidate the clinical significance of sympathetic nerve degeneration in reimplantation failure.     

The simplified two-pipette technique is more efficient than the conventional three-pipette method for blastomere biopsy in human embryos

Kell and Kx are two quantitatively minor proteins from the human erythrocyte membrane which carry blood groups antigens and are thought to be a metalloprotease and a membrane transporter, respectively. In the red cell membrane, these proteins form a complex stabilized by disulfide bond(s). Phosphorylation status of these proteins was studied, in the presence or absence of effectors of several kinases, either on intact cells incubated with [32P]-orthophosphate or on ghosts incubated with [gamma-32P]ATP. Purification of Kell-Kx complex, by immunochromatography on an immobilized human monoclonal antibody of Kell blood group specificity allowed to establish that (i) neither protein is phosphorylated on tyrosine; (ii) the Kell protein is a putative substrate for Casein Kinase II (CKII) and Casein Kinase I (CKI) but not for protein kinase C (PKC), whereas Kx protein is phosphorylated by CKII and PKC but not by CKI; (iii) Protein Kinase A neither phosphorylates the Kell nor the Kx proteins.     

Verminderung des Gehaltes von Blei und anderen Elementen in Wein mit Hilfe von Pectins?ure

Zusammenfassung Der Bleigehalt von Wein kann durch Zusatz von Pectinsäure (PS) vermindert werden. Die Wirksamkeit der Bleiverminderung durch PS hängt von der Qualitätsstufe des Weines ab. In Auslesewein (Wein A) senkten 6250 mg PS/1 den Bleigehalt in 24 h von 0,88 mg/l auf 0,28 mg/l und in Spätlese (Wein B) von 0,83 mg/l auf 0,06 mg/1. Unter den gleichen Bedingungen nahm in Wein A der Gehalt an Fe, Zn und Cu von 8,85 mg/l auf 7,05 mg/1, von 4,75 mg/l auf 1,25 mg/l and von 0,67 mg/l auf 0.57 mg/l ab; bei Wein B reduzierte sich der Gehalt von Fe, Zn und Cu von 6,70 mg/l auf 5,41 mg/1, von 1,17 mg/l auf 0,28 mg/l und von 0,46 mg/l auf 0,28 mg/1. Durch Filtration des Weines wurde PS nahezu quantitativ entfernt. Eine geschmackliche Beeinträchtigung des Weines durch PS ist bei 750 mg and 1500 mg PS/1 nicht feststellbar, jedoch bei 6 250 mg PS/1 nicht auszuschließen. Aufgrund ihrer hohen Bindungsaffinität zu Blei scheint PS geeignet, Blei auch aus anderen flüssi-gen Lebensmitteln zu entfernen.

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Reduction of lead content and of other metals in wine by means of pectic acid

Summary A procedure for reducing the Pb content in wines containing high levels of Pb is described. The reduction of Pb by means of pectic acid (PA) depends on the quality grade of the wine. In Auslese (wine A) 6250 mg PA/l diminished Pb content in 24 h from 0.88 mg/l to 0.28 mg/1; in Spatlese (wine B) from 0.83 mg/l to 0.06 mg/1. Under the same conditions the content of Fe, Zn, Cu decreased in wine A from 8.85 mg/l to 7.05 mg/1, from 4.75 mg/l to 1.25 mg/1, from 0.67 mg/l to 0.57 mg/l and in wine B from 6.70 mg/l to 5.41 mg/1, from 1.17 mg/l to 0.28 mg, 0.46 mg/l to 0.28 mg/l, respectively. PA is removed almost quantitatively by filtration. Sensory properties of treated wines were unchanged with concentrations of PA of 750 mg and 1500 mg/l. A slight effect on taste at 6250 mg PA/l wine cannot be excluded. On account of its high affinity to Pb, PA will probably remove Pb from other liquid foods as well.

     

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.     

Effect of Grain Size on Mechanical Properties of Submicrometer 3Y-TZP: Fracture Strength and Hydrothermal Degradation

This paper considers fracture strength, fracture origins, and hydrothermal degradation of 3Y-TZP with grain sizes in the range of 110–480 nm. Biaxial fracture strength testing was used to show that the fracture strength increases with grain size and is governed by the concurrent change in fracture toughness. Hydrothermal degradation was studied by means of fractography, Raman microscopy and its effect on fracture strength. Up to 200 nm grain size, hydrothermal degradation of strength is limited. Larger grain sizes exhibit either premature failure or an increase in strength. A surface transformation zone was found to be responsible for both phenomena.     

The Estimation of the Molecular Weight of Polytetrafluoroethylene Based on the Heat of Crystallisation. A Comment on Suwa's Equation

Summary: The influence of number‐average molecular weight ranging from 1.4 · 10⁴ to 1.2 · 10⁶ g/mol on the thermal behaviour of polytetrafluoroethylene (PTFE) has been studied. Samples have been prepared by radiation‐induced degradation of commercial PTFE. The molecular weight has been calculated using end‐group concentration determined by infrared (IR) spectroscopy and ¹⁹F solid‐state nuclear magnetic resonance (NMR) spectroscopy. Melting and crystallisation heats were investigated by differential scanning calorimetry (DSC). The results have been discussed with respect to quantitative relationships between number‐average molecular weight and heat of crystallisation of PTFE described in the literature. The molecular weight calculated from Suwa's equation, which is often used in the literature, has been found to be too low.

Concentration of end‐groups and the molecular weight of PTFE versus the irradiation dose.     

Reinigung lösungsmittelhaltiger Abluft – alternative Möglichkeiten

Purification of solvents containing air – Alternative methods. Different processes are used for the purification of solvents containing air: condensation, absorption, adsorption, combustion, membrane permeation, and biofilters or bioscrubbers. The processes will be explained by examples. The specifications required by “TA Luft” often cannot be reached only by condensation and membrane permeation. The success of absorption depends on the scrubbing liquid. Glycol ethers are useful scrubbing liquids – especially for chlorinated hydrocarbons. The choice of the process depends on the volume flow rate, the solvent concentration, and the kind of solvent. Recycling of the solvents reduces the costs of the process.     

Nitrate Radicals in Tropospheric Chemistry

Nitrate radicals are being recognized as key intermediates in a growing list of important chemical processes in the atmosphere. Here, the role of nitrate radicals (NO₃) in tropospheric chemistry is discussed, with special emphasis on results from field measurements, most of which have been made by differential optical absorption spectroscopy (DOAS), with matrix-isolation electron spin resonance being an alternative technique. Nitrate radicals were observed in the atmosphere at peak mixing ratios of 350 ppt. Long-term observation of NO₃ shows that 24-h averages in rural air masses are closer to a few ppt. Nevertheless, the NO₃ radical plays an important role in the non-photochemical conversion of NO_x to HNO₃. Also, NO₃ is a strong oxidizing agent and initiates the night-time removal of atmospheric trace species such as olefins, aromatic hydrocarbons, and organic sulfur compounds. Finally, night-time peroxy radical production and release of reactive halogen species from sea salt aerosol might be initiated by NO₃ reactions.