Early treatment decisions with interferon-alfa therapy in early chronic-phase chronic myelogenous leukemia

PURPOSE: To determine, in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) on interferon alfa (IFNalpha), whether combining pretreatment characteristics and early response profiles would distinguish patients with differential benefits that would allow better decisions on subsequent therapy. PATIENTS AND METHODS: A total of 274 patients treated from 1982 through 1990 with IFNalpha regimens were analyzed. A second group of 137 patients treated with IFNalpha and low-dose cytarabine (ara-C) between 1990 and 1994 was later used to confirm the guidelines derived from the original study group analysis. Patients' pretreatment factors and response to IFNalpha therapy at 3, 6, and 12 months were analyzed in relation to subsequent achievement of major cytogenetic response. After univariate analysis of prognostic factors, a multivariate analysis selected, at 6 months, independent pretreatment factors that added to the response status in predicting subsequent outcome. The results were then applied at the 3- and 12-month periods and confirmed in the subsequent population. RESULTS: Response to IFNalpha therapy at 3, 6, and 12 months was a significant predictor of later major cytogenetic response. The presence of splenomegaly > or = 5 cm below the costal margin (BCM) or thrombocytosis > or = 700 x 10(9)/L pretreatment added significant independent prediction to response. At 6 months, patients with a partial hematologic response (PHR) or resistant disease had a less than 10% chance of achieving a later major cytogenetic response, as were those in complete hematologic response (CHR) and who had pretreatment splenomegaly and thrombocytosis. Applying the model at 3 months showed that only patients with < or = PHR and pretreatment splenomegaly or thrombocytosis at 3 months had such a low major cytogenetic response rate. Finally, at 12 months, patients with CHR still had a 15% to 25% chance of having a major cytogenetic response later if they did not have pretreatment splenomegaly and thrombocytosis. CONCLUSION: This analysis allows better selection of patients with Ph-positive CML on IFNalpha therapy for continuation of IFNalpha versus changing therapy early in the course of CML. For treatment programs that choose to change patients to other investigational therapies (eg, intensive chemotherapy and/or autologous stem-cell transplantation [SCT]), baseline outcome expectations are provided for patients continued on IFNalpha therapy, against which the results of new approaches can be compared.     

Identification of the chromosome 14 origin of a C-negative marker associated with a 14q32 deletion by chromosome painting

A constitutional chromosome 14 rearrangement was observed in a female with a psychodevelopmental disorder. Karyotype analysis using a variety of chromosome techniques, QFQ, GTG, CBG, Ag-NOR and DA-DAPI, showed a deletion of chromosome 14q32.1-qter region in association with a supernumerary marker chromosome. The marker, resembling a submetacentric, approximately half the size of a G group chromosome is C band and Ag-NOR negative. The heteromorphism of the satellites showed that the deleted chromosome 14 is paternal in origin. Chromosome painting using an Alu-PCR probe specific for the human chromosome 14 and fluorescent in situ hybridization (FISH) showed that the marker contains chromosome 14q32 sequences. It is likely that the marker was generated from the deleted chromosome 14 region through a complex rearrangement.     

Casein haplotype structure in five Italian goat breeds

The aim of this work was to investigate the genetic structure of the casein gene cluster in 5 Italian goat breeds and to evaluate the haplotype variability within and among populations. A total of 430 goats from Vallesana, Roccaverano, Jonica, Garganica, and Maltese breeds were genotyped at alphas1-casein (CSN1S1), alphas2-casein, (CSN1S2), beta-casein (CSN2), and kappa-casein (CSN3) loci using several genomic techniques and milk protein analysis. Casein haplotype frequencies were estimated for each breed. Principal component analysis was carried out to highlight the relationship among breeds. Allele and haplotype distributions indicated considerable differences among breeds. The haplotype CSN1S1*F- CSN1S2*F-CSN3*D occurred in all breeds with frequencies >0.100 and was the most common haplotype in the Southern breeds. A high frequency of CSN1S1*0-CSN1S2*C-CSN3*A haplotype was found in Vallesana population (0.162). Principal component analysis clearly separated the Northern and Southern breeds by the first component. The variability of the caprine casein loci and variety of resulting haplotypes should be exploited in the future using specific breeding programs aiming to preserve biodiversity and to select goat genetic lines for specific protein production.     

Self‐Immobilizing Precatalysts: Norbornene‐Bridged Zirconium ansa‐Metallocenes

We report here the synthesis of new tethered biscyclopentadienyl and bisindenyl zirconocenes, bearing one unsaturation on the interannular bridge, and their use as self‐immobilizing catalysts. They proved to be active catalysts towards ethylene polymerization in solution, with activities comparable to those displayed by commercial rac‐Et(Ind)₂ZrCl₂. When tested as self‐polymerization catalysts under suitable experimental conditions, they gave colored precipitates that, once reactivated with MAO, were significantly active in ethylene polymerization, although lower than those of the corresponding catalytic systems in solution. The molecular weights of the produced polymers were similar to those obtained with the same catalysts in solution, but their distribution resulted to be broader, with values typical of heterogeneous catalytic systems. From ¹³C NMR studies we had the first spectroscopic evidence of the actual incorporation of a metallocene of this type into a polymeric chain.     

Experimental Missions in W-Band: A Small LEO Satellite Approach

W-band (75-110 GHz) is proposed nowadays as a valuable alternative to intensively-exploited Ku- and Ka-bands for high-speed transmission over satellite networks. In such a framework, some experiments are being carried out, which are targeted to verify the feasibility of exploitation of W-band for broadband service deployment. From a theoretical viewpoint, the large bandwidth availability and the scarce amount of interference typical of W-band should guarantee high capacities. Nevertheless, many crucial aspects are still to be carefully investigated, e.g., signal propagation issues, RF impairments, choice of modulation and coding, efficient antenna design, etc. In this paper, an overview is made on the low Earth orbit (LEO) nano-satellite mission in-orbit key-test and validation of W-band (IKNOW). IKNOW mission is an ongoing advanced feasibility study part of an Italian Space Agency Project, named W-band analysis and verification (WAVE), coordinated by the Department of Electronic Engineering, University of Rome ldquoTor Vergatardquo. The main objective of the IKNOW mission is to tackle some of the unexplored critical aspects concerning W-band satellite transmission. In such a perspective, IKNOW should be regarded as a ldquopilot mission,rdquo whose results will be used for a first uplink-downlink satellite channel characterization, in-orbit validation of W-band technology, and space qualification processes. This paper is focused on the research work carried out in a preliminary phase of the IKNOW study and will also consider a number of elements related to the mission configuration, payload architecture, link analysis, potential RF impairment factors, and atmospheric effects. Proposed analysis and preliminary results shown can provide to interested readers the basic guidelines that will drive the practical implementation of IKNOW mission, as well as the most relevant issues to be faced by future developers of W-band missions using small LEO satellites.     

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.     

Atomic force microscopy characterization of Xenopus laevis oocyte plasma membrane

We used atomic force microscopy (AFM) to characterize the plasma membrane of Xenopus laevis oocytes. The samples were prepared according to novel protocols, which allowed the investigation of the extra- and intracellular sides of the membrane, both of which showed sparsely distributed spherical-like protrusions. Regions with comparably sized and densely packed structures arranged in an orderly manner were visualized and dimensionally characterized. In particular, two different arrangements, hexagonal and square packing, were recognizable in ordered regions. The lateral dimension of structures visualized on the external side had a normal distribution centered on 25.5 +/- 0.3 nm (mean value +/- SE), whereas that on the intracellular side showed a normal distribution centered on 30.2 +/- 0.8 nm. The height of the protrusions was 2-5 nm on the external side and 1-3 nm on the intracellular side. The mean number of structures on the external and intracellular sides of the plasma membrane was about 1000 microm(-2) and 850 microm(-2) respectively. Trypsin treatment greatly decreased the size of the membrane protrusions, thus confirming the proteic nature of the structures. These results show that AFM is a useful tool for structural characterization of proteins in a native eukaryotic membrane.     

Potential allelochemicals fromRuta graveolens L. and their action on radish seeds

An aqueous extract ofRuta graveolens L. (250 g/liter) was tested for its allelopathic activity in vitro on radish germination and radicle growth in light and darkness. It caused a delay in the onset and a decrease in the rate of germination (40%) in the light. The photoinhibition of germination was accompanied by an inhibition of water uptake into the seed. Furthermore, the inhibition of radicle growth was slightly higher in the light than in darkness. Three potential allelochemicals, biologically active in the light, were isolated from the extract: 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 4-hydroxy-coumarin at concentrations of 10^–4 M, 2×10^–4 M, and 0.4 ×10^–5 M respectively. At a concentration of 2×10^–4 M, 5-MOP was the most potent inhibitor, decreasing radish germination to 32% and radicle growth to 17% with respect to control. Microscopic observations of radish seeds treated with 5-MOP suggest that this substance changes the swelling of the seed coat and aleurone layer, which precedes radicle protrusion.     

Antioxidant activity of virgin olive oil phenolic compounds in a micellar system†

The antioxidant activity of two virgin olive oils, obtained from the same olive (Olea europaea sativa) batch but processed with different hammer crushing conditions, was evaluated by measuring their protective action towards linoleic acid peroxidation in a micellar system. The antioxidant efficiency (AE) of the oil phenolic fraction was higher when the olives were processed with a higher hammer crusher rotation rate. HPLC analysis demonstrated that one of the main derivatives of oleuropein, indicated as 3,4-DHPEA-EDA (the dialdehydic form of elenolic acid linked with 3,4-dihydroxyphenylethanol), is present only in the oil with higher AE. 3,4-DHPEA-EDA showed the greatest antioxidant ability among virgin olive oil phenols. Its greater efficiency in the micellar system in comparison with 3,4-dihydroxyphenylethanol (3,4-DHPEA) is related to its greater lipophilicity. It is suggested that the behaviour in the water–micellar environment is representative of that in a real system such as tomato-based sauce with added virgin olive oil. © 1999 Society of Chemical Industry     

Fluoro-functionalized PLA polymers as potential water-repellent coating materials for protection of stone

A series of sixteen fluoro-functionalized poly(lactic acid)s were synthesised using two commercial fluorinated alcohols [3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol and 4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)benzyl alcohol] as co-initiators in the ring-opening polymerization of L-lactide and rac-lactide (the racemic mixture of L- and D-lactide) catalyzed by Tin(II) 2-ethylhexanoate. The polymers were characterized by NMR, IR, GPC, DSC and tested as potential protective coating for stone. The performances were comparatively evaluated in terms of water protection efficacy and colour changes of the treated stone. Furthermore, the photo-stability of nine selected polymers under Solar Box condition was also investigated. It has been shown that the presence of fluorine makes the stone more water-repellent. The polymers showed also interesting photo-stability and some of them provided a behavior close to PLA-FLK-PLA block copolymers recently reported in the literature, in spite of their lower fluorine content © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012