Objectives. This study was designed to evaluate the changes in intrastent and angiographic dimensions when intravascular ultrasound imaging is used to direct the deployment of balloon-expandable ...Palmaz-Schatz stents in coronary arteries and saphenous vein grafts.
Background. Intravascular ultrasound provides more information than angiography in the imaging of intravascular structures. Previous studies have shown that obtaining a larger lumen (greater “acute gain”) with coronary interventions such as stenting leads to less restenosis and subacute thrombosis. It is not clear whether the information obtained by intravascular ultrasound can be used to obtain a greater acute gain in lumen dimensions.
Methods. Forty consecutive patients undergoing Palmaz-Schatz stent implantation had intravascular ultrasound imaging performed after a good angiographic appearance was obtained. If the stent did not appear adequately expanded by intravascular ultrasound, or if the struts were poorly opposed to the arterial wall, further stent dilation with larger balloons or higher pressure inflations were performed. Twenty-nine patients had subsequent intravascular ultrasound imaging. Intrastent diameters and areas were compared from the initial to the final intravascular ultrasound studies.
Results. Of the 40 patients studied, only 5 (13%) had an adequate result by intravascular ultrasound despite an acceptable angiographic appearance in all patients. Six additional patients did not undergo subsequent intravascular ultrasound imaging. The other 29 patients all demonstrated a significant increase in intrastent minimal diameter (mean 19%), major diameter (11%) and cross-sectional area (34%) (p < 0.001 for all measurements).
Conclusions. The use of intravascular ultrasound imaging in the deployment of balloon-expandable Palmaz-Schatz stents leads to a significant increase in intrastent dimensions (greater “acute gain”).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Doxorubicin-overproducing strains of Streptomyces peucetius ATCC 29050 can be obtained through manipulation of the genes in the region of the doxorubicin (DXR) gene cluster that contains dpsH, the ...dpsG polyketide synthase gene, the putative dnrU ketoreductase gene, dnrV, and the doxA cytochrome P-450 gene. These five genes were characterized by sequence analysis, and the effects of replacing dnrU, dnrV, doxA, or dpsH with mutant alleles and of doxA overexpression on the production of the principal anthracycline metabolites of S. peucetius were studied. The exact roles of dpsH and dnrV could not be established, although dnrV is implicated in the enzymatic reactions catalyzed by DoxA, but dnrU appears to encode a ketoreductase specific for the C-13 carbonyl of daunorubicin (DNR) and DXR or their biosynthetic precursors. The highest DXR titers were obtained in a dnrX dnrU (N. Lomovskaya, Y. Doi-Katayama, S. Filippini, C. Nastro, L. Fonstein, M. Gallo, A. L. Colombo, and C. R. Hutchinson, J. Bacteriol. 180:2379-2386, 1998) double mutant and a dnrX dnrU dnrH (C. Scotti and C. R. Hutchinson, J. Bacteriol. 178:7316-7321, 1996) triple mutant. Overexpression of doxA in a doxA::aphII mutant resulted in the accumulation of DXR precursors instead of in a notable increase in DXR production. In contrast, overexpression of dnrV and doxA jointly in the dnrX dnrU double mutant or the dnrX dnrU dnrH triple mutant increased the DXR titer 36 to 86%.
In this randomized trial involving patients with relapsing multiple sclerosis who had had relapses despite treatment with interferon, natalizumab in combination with interferon was more effective ...than interferon alone. After two years, the probability of sustained disability progression was 23 percent with combination treatment and 29 percent with interferon alone. Progressive multifocal leukoencephalopathy developed in two patients receiving combination treatment, and one of these two patients died of this serious complication of therapy.
The adhesion molecule α
4
β
1
integrin is a key initiator of the inflammatory cascade involved in the pathogenesis of multiple sclerosis.
1
–
4
Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) is the first α
4
integrin antagonist in a new class of selective adhesion-molecule inhibitors for the treatment of multiple sclerosis. Natalizumab binds to α
4
integrin on the surface of leukocytes, inhibiting their migration into the brain and thereby reducing inflammation.
Current disease-modifying therapies for relapsing–remitting multiple sclerosis (interferon beta and glatiramer acetate) are only partially effective,
5
–
8
and most patients with multiple sclerosis have breakthrough disease activity . . .
We sought to investigate whether genetic effects on response to TNF inhibitors (TNFi) in rheumatoid arthritis (RA) could be localised by considering known genetic susceptibility loci for relevant ...traits and to evaluate the usefulness of these genetic loci for stratifying drug response.
We studied the relation of TNFi response, quantified by change in swollen joint counts ( Δ SJC) and erythrocyte sedimentation rate ( Δ ESR) with locus-specific scores constructed from genome-wide assocation study summary statistics in 2938 genotyped individuals: 37 scores for RA; scores for 19 immune cell traits; scores for expression or methylation of 93 genes with previously reported associations between transcript level and drug response. Multivariate associations were evaluated in penalised regression models by cross-validation.
We detected a statistically significant association between Δ SJC and the RA score at the
locus (p=0.0004) and an inverse association between Δ SJC and the score for expression of CD39 on CD4 T cells (p=0.00005). A previously reported association between CD39 expression on regulatory T cells and response to methotrexate was in the opposite direction. In stratified analysis by concomitant methotrexate treatment, the inverse association was stronger in the combination therapy group and dissipated in the TNFi monotherapy group. Overall, ability to predict TNFi response from genotypic scores was limited, with models explaining less than 1% of phenotypic variance.
The association with the CD39 trait is difficult to interpret because patients with RA are often prescribed TNFi after failing to respond to methotrexate. The CD39 and
pathways could be relevant for targeting drug therapy.
This report describes a Chlamydomonas reinhardtii mutant that lacks Rubisco activase (Rca). Using the BleR (bleomycin resistance) gene as a positive selectable marker for nuclear transformation, an ...insertional mutagenesis screen was performed to select for cells that required a high-CO2 atmosphere for optimal growth. The DNA flanking the BleR insert of one of the high-CO2-requiring strains was cloned using thermal asymmetric interlaced-polymerase chain reaction and inverse polymerase chain reaction and sequenced. The flanking sequence matched the C. reinhardtii Rca cDNA sequence previously deposited in the National Center for Biotechnology Information database. The loss of a functional Rca in the strain was confirmed by the absence of Rca mRNA and protein. The open reading frame for Rca was cloned and expressed in pSL18, a C. reinhardtii expression vector conferring paromomycin resistance. This construct partially complemented the mutant phenotype, supporting the hypothesis that the loss of Rca was the reason the mutant grew poorly in a low-CO2 atmosphere. Sequencing of the C. reinhardtii Rca gene revealed that it contains 10 exons ranging in size from 18 to 470 bp. Low-CO2-grown rca1 cultures had a growth rate and maximum rate of photosynthesis 60% of wild-type cells. Results obtained from experiments on a cia5 rca1 double mutant also suggest that the CO2-concentrating mechanism partially compensates for the absence of an active Rca in the green alga C. reinhardtii.
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The GAPS Programme with HARPS-N at TNG Barbato, D.; Sozzetti, A.; Biazzo, K. ...
Astronomy and astrophysics (Berlin),
01/2019, Volume:
621
Journal Article
Peer reviewed
Context.
Statistical studies of exoplanets have shown that giant planets are more commonly hosted by metal-rich dwarf stars than low-metallicity stars, while no such correlation is evident for lower ...mass planets. The search for giant planets around metal-poor stars and the estimate of their occurrence
f
p
is an important element in providing support to models of planet formation.
Aims.
We present results from the HARPS-N search for giant planets orbiting metal-poor (− 1.0 ≤Fe/H ≤−0.5 dex) stars in the northern hemisphere, complementing a previous HARPS survey on southern stars in order to update the estimate of
f
p
.
Methods.
High-precision HARPS-N observations of 42 metal-poor stars were used to search for planetary signals to be fitted using differential evolution Markov chain Monte Carlo single-Keplerian models. We then joined our detections to the results of the previous HARPS survey on 88 metal-poor stars to provide a preliminary estimate of the two-hemisphere
f
p
.
Results.
We report the detection of two new giant planets around HD 220197 and HD 233832. The first companion has Msin
i
= 0.20
−0.04
+0.07
M
Jup
and an orbital period of 1728
−80
+162
days, and for the second companion, we find two solutions of equal statistical weight with periods of 2058
−40
+47
and 4047
−117
+91
days and minimum masses of 1.78
−0.06
+0.08
and 2.72
−0.23
+0.23
M
Jup
, respectively. Joining our two detections with the three from the southern survey, we obtain a preliminary and conservative estimate of the global frequency of
f
p
= 3.84
−1.06
+2.45
% for giant planets around metal-poor stars.
Conclusions.
The two new giant planets orbit dwarf stars at the metal-rich end of the HARPS-N metal-poor sample. This corroborates previous results that suggested that giant planet frequency is still a rising function of the host star Fe/H. We also note that all detections in the overall sample are giant long-period planets.
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In this study, atmospheric pressure non‐thermal plasma treatment of electrospun poly(L‐lactic acid) scaffolds is used to improve scaffold hydrophilicity and to introduce carboxyl groups on scaffold ...surface. Thermo‐mechanical properties, morphology, hydrophilicity, and water uptake of the plasma‐treated scaffolds are studied. The amount of carboxyl functional groups on the scaffold surface is evaluated using fluorescein isothiocyanate conjugation and microdensitometry. The effect of plasma treatment on mouse embryonic fibroblast morphology is assessed through image analysis. Results show an enhancement of scaffold biocompatibility, demonstrating that atmospheric plasma technology is a flexible process that can be integrated in “in‐line” procedures of biomaterial fabrication and functionalization.
Non‐thermal atmospheric pressure plasma is applied for surface modification of nanofibrous electrospun PLLA scaffolds. The plasma treatment causes a notable increase of scaffold hydrophilicity and wettability and the introduction of carboxylic functional groups. Mouse embryonic fibroblast cells cultured on plasma treated scaffolds show a more elongated and “dendritic” morphology and a higher vitality than cells cultured on pristine scaffolds.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK